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Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.

Background: Constipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation., Methods: Fecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, α-diversity analysis, β-diversity analysis, species difference analysis, and predictive functional analysis., Results: The alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus&#95;gnavus&#95;group, Lachnospiraceae&#95;unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales&#95;unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella&#95;7, Gordonibacter, Mitochondria&#95;unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p<0.05). Compared with non-constipation group, the Kineothrix, Rhodopirellula, Weissella were significantly lower in constipation group (p<0.05). The predictive functional analysis revealed that compared with non-constipation group, constipation group was significantly enriched in pathways associated with pyruate metabolism, flavonoid biosynthesis., Conclusions: This study describes for the first time the intestinal microbiome characteristics of maintenance hemodialysis patients with constipation. The results of this study suggest that there is a difference in the intestinal flora between maintenance hemodialysis patients with constipation and maintenance hemodialysis patients without constipation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Chen, Zhu, Wu, Lu, Zhou, Zhu, Xu, Liu, Zhu and Lin.)

Background: This study aimed to characterize the oral and gut microbiota in prediabetes mellitus (Pre-DM) and type 2 diabetes mellitus (T2DM) patients while exploring the association between tongue manifestations and the oral-gut microbiota axis in diabetes progression., Methods: Participants included 30 Pre-DM patients, 37 individuals with T2DM, and 28 healthy controls. Tongue images and oral/fecal samples were analyzed using image processing and 16S rRNA sequencing. Machine learning techniques, including support vector machine (SVM), random forest, gradient boosting, adaptive boosting, and K-nearest neighbors, were applied to integrate tongue image data with microbiota profiles to construct predictive models for Pre-DM and T2DM classification., Results: Significant shifts in tongue characteristics were identified during the progression from Pre-DM to T2DM. Elevated Firmicutes levels along the oral-gut axis were associated with white greasy fur, indicative of underlying metabolic changes. An SVM-based predictive model demonstrated an accuracy of 78.9%, with an AUC of 86.9%. Notably, tongue image parameters (TB-a, perALL) and specific microbiota ( Escherichia , Porphyromonas-A ) emerged as prominent diagnostic markers for Pre-DM and T2DM., Conclusion: The integration of tongue diagnosis with microbiome analysis reveals distinct tongue features and microbial markers. This approach significantly improves the diagnostic capability for Pre-DM and T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Deng, Dai, Liu, Tu, Cui, Hu, Qiu, Jiang and Xu.)

Objectives: Recent studies have increasingly demonstrated that a multiplatform water environment combined with lard gavage is an effective method for establishing a mouse model of diarrhea. However, the interactions between intestinal microorganisms and diarrhea, as well as the relationships among energy metabolism, fluid balance, and gastrointestinal function in this model, remain poorly understood., Methods: Building on previous research, this study aimed to optimiz and replicate a multiplatform water environment combined with a lard gavage model. Male Kunming mice, free of specific pathogens, were randomly divided into four groups: a normal control group (ZC), a standing group (ZL), a standing combined with lard group (ZLZ), and a standing combined with internal and external wet conditions group (ZLZS). The mice in the ZL, ZLZ, and ZLZS groups were subjected to 4 hours of daily standing in a custom-designed multiplatform water environment. Starting on day 8, mice in the ZLZ and ZLZS groups were gavaged with lard (0.4 mL per session, twice daily) for 7 consecutive days, while those in the ZLZS group were additionally exposed to a wet litter environment (50 g/100 mL). The ZC and ZL groups received equal volumes of sterile water via gavage. The microbiota in the small intestine, as well as serum levels of cAMP, cGMP, VIP, Gas, and D-xylose, were analyzed., Results: Compared with the ZLZ group, the ZLZS group showed significantly lower serum levels of cAMP/cGMP ( p <0.01) and Gas ( p <0.01). D-xylose levels were lower in the ZL, ZLZ, and ZLZS groups compared to the ZC group, while VIP levels were significantly higher in the ZL and ZLZS groups ( p <0.01). Moverover, Corynebacterium , Empedobacter , and Pseudochrobactrum were identified as characteristic bacterial genera in the ZLZS group. The mechanism by which the small intestinal microbiota induces diarrhea was linked to the biosynthesis of secondary bile acids., Conclusion: A multiplatform water environment combined with lard gavage can effectively induce diarrhea, and the addition of an external wet environment exacerbates this condition by affecting small intestinal contents microbiota and other functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Yu, Xie, Guo, Wu, Tian, Wang, Zhou and Cai.)

Endometriosis (EMT) has a significant impact on women's physical and mental health. In this study, high-throughput sequencing technology was employed to detect differences in gut microbiota between EMT patients and healthy individuals (CTL). Additionally, Spearman correlation analysis was utilized to analyze the correlation between different bacterial genera and EMT biomarkers (CA125 and CA199). The results demonstrated that at the phylum level, the relative abundances of Proteobacteria and Desulfobacterota&#95;G&#95;459546 in the EMT group were significantly higher than those in the CTL group, while the relative abundances of Bacteroidota and Firmicutes&#95;A in the EMT group were significantly lower than those in the CTL group. At the genus level, the relative abundances of Burkholderiales and Sphingomonadales in the EMT group were significantly higher than those in the CTL group, while the relative abundances of Bacteroidales and Roseburia in the EMT group were significantly lower than those in the CTL group. The correlation analysis results show that CA125 and CA199 are significantly positively correlated with Burkholderiales and Sphingomonadales , and significantly negatively correlated with Bacteroidales , Oscillospirales , and Roseburia . The PICRUSt2 results show that the relative abundance in the cell motility and xenobiotics biodegradation and metabolism pathways in the EMT group was higher than that in the CTL group, while the relative abundance in the translation, replication and repair, folding, sorting and degradation, metabolism of terpenoids and polyketides and metabolism of cofactors and vitamins pathways in the EMT group was lower than that in the CTL group. In brief, there is a close correlation between the imbalance of gut microbiota and the onset of EMT. The intestinal microbiota has great significance broad prospects for the prevention, diagnosis and treatment of EMT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Yan and Han.)

Background: This article employs bibliometric methods and visual maps to delineate the research background, collaborative relationships, hotspots, and trends in the study of gut fungi in human diseases and health., Methods: Publications related to human gut fungi were retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, R software and Microsoft Excel were employed to generate visual representations illustrating the contributions made by countries/regions, authors, organizations, and journals. Employing VOSviewer and CiteSpace, we conducted a comprehensive analysis of the retrieved publications, revealing underlying tendencies, research hotspots, and intricate knowledge networks., Results: This study analyzed a total of 3,954 publications. The United States ranks first in the number of published papers and has the highest number of citations and h-index. Mostafa S Elshahed is the most prolific author. The University of California System is the institution that published the most papers. Frontiers In Microbiology is the journal with the largest number of publications. Three frequently co-cited references have experienced a citation burst lasting until 2024., Conclusion: Advancements in sequencing technologies have intensified research into human gut fungi and their health implications, shifting the research focus from gut fungal infections towards microbiome science. Inflammatory bowel diseases and Candida albicans have emerged as pivotal areas of interest in this endeavor. Through this study, we have gained a deeper insight into global trends and frontier hotspots within this field, thereby enhancing our understanding of the intricate relationship between gut fungi and human health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gong, Yu, Qu, Li, Liu and Zhao.)

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of hepatocellular carcinoma (HCC) worldwide. Over the years, Perilipin 5 (PLIN5) has been recognized as a key regulator of both MAFLD and HCC development. In our previous studies we demonstrated that deficiency in Plin5 reduces the severity of MAFLD and HCC in mice. Interestingly, it has been established that patients with MAFLD and HCC exhibit various changes in their gut microbiome profiles. The gut microbiome itself has been shown to play a role in modulating carcinogenesis and the immune response against cancer., Methods: Therefore, we conducted a study to investigate the alterations in fecal microbiome composition in wild type (WT) and Plin5 -deficient ( Plin5 -/- ) mice models of MAFLD and MAFLD-induced HCC (MAFLD-HCC). We utilized 16S rRNA gene sequencing analysis to profile the composition of gut bacteria in fecal samples., Results: Notably, we discovered that the absence of Plin5 alone is already associated with changes in gut microbiota composition. Moreover, feeding the mice a Western diet (WD) resulted in additional microbial alterations. Interestingly, Plin5 -/- animals exhibited an enrichment of the beneficial taxa Lactobacillus in both animal models., Discussion: Our findings identify Plin5 as a major regulator of gut microbiota during the development of MAFLD and MAFLD-HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Krizanac, Štancl, Mass-Sanchez, Karlić, Moeckel, Lammers, Asimakopoulos and Weiskirchen.)

Although the importance of the microbiome in the context of tick biology and vector competence has recently come into a broader research focus, the field is still in its infancy and the complex ecological interactions between the tick residential bacteria and pathogens are obscure. Here, we show that an environmentally acquired gut bacterium has the potential to impair Borrelia afzelii colonization within the tick vector through a secreted metalloprotease. Oral introduction of either Bacillus cereus LTG-1 isolate or its purified enhancin ( Bc Enhancin) protein significantly reduces B. afzelii burden in the guts of Ixodes ricinus ticks. This effect is attributed to the ability of Bc Enhancin to degrade a glycan-rich peritrophic matrix (PM), which is a gut protective barrier essential for Borrelia survival. Our study highlights the importance of the gut microbiome in determining tick vector competence and provides a deeper mechanistic insight into the complex network of interactions between Borrelia , the tick, and the tick microbiome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hodžić, Veinović, Alić, Seki, Kunert, Nikolov, Sukara, Šupić, Tomanović and Berry.)

The gut microbiota plays a crucial role in food webs, carbon cycling, and related elements. Exopalaemon annandalei and Exopalaemon carinicauda are two important forage species in the Yangtze River estuary with extremely similar living habits and morphological characteristics. Exploring the microorganisms in the guts of these two shrimp species can help us understand the survival status of forage species and gut microbiota in the Yangtze River estuary. Therefore, this study analyzed the similarities and differences in the intestinal flora of E. annandalei and E. carinicauda through high-throughput sequencing of 16S rRNA gene amplicons. The results showed that the dominant bacteria in the intestinal flora of E. annandalei and E. carinicauda at the phylum level were Proteobacteria and Firmicutes, respectively. At the genus level, the intestinal flora had higher concentrations of Psychrobacter , Bacillus , Pseudomonas , Acinetobacter , and Macrococcus . In both shrimp species, the contents of Acinetobacter and Macrococcus were higher in spring than in winter. The most important potential functions of the intestinal microbiota were amino acid metabolism and purine metabolism. Additionally, the functions of metabolism and diseases in the intestinal microbiota of E. annandalei were greatly influenced by the season. Furthermore, the experimental results indicated that a lower ratio of Firmicutes to Bacteroidetes was associated with a larger body weight in shrimp. Overall, this study provides a theoretical reference for understanding the intestinal bacterial community of shrimp in estuaries and the healthy cultivation of E. annandalei and E. carinicauda ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Feng, Han, Zhang, Chen and Wu.)

Through complex interactions with the host's immune and physiological systems, gut bacteria play a critical role as etiological agents in a variety of human diseases, having an impact that extends beyond their mere presence and affects the onset, progression, and severity of the disease. Gaining a comprehensive understanding of these microbial interactions is crucial to improving our understanding of disease pathogenesis and creating tailored treatment methods. Correcting microbial imbalances may open new avenues for disease prevention and treatment approaches, according to preliminary data. The gut microbiota exerts an integral part in the pathogenesis of numerous health conditions, including metabolic, neurological, renal, cardiovascular, and gastrointestinal problems as well as COVID-19, according to recent studies. The crucial significance of the microbiome in disease pathogenesis is highlighted by this role, which is comparable to that of hereditary variables. This review investigates the etiological contributions of the gut microbiome to human diseases, its interactions with the host, and the development of prospective therapeutic approaches. To fully harness the benefits of gut microbiome dynamics for improving human health, future research should address existing methodological challenges and deepen our knowledge of microbial interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Islam, Mahbub, Hong and Chung.)

Background: High-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible association between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remains unclear., Methods: Hamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal, plasma and liver samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and relevant metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids., Results: The gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters. Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters. Plasma and liver metabolomics further indicated the upregulation and enrichment of glycerolipid metabolites in HFD hamsters. The Faecalibaculum , Allobaculum , and Eubacterium genera were positively correlated with plasma glycerolipid metabolites and lipid indices., Conclusion: The findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Hu, Du, Yu, Du, Li, Li, Wang, Gao, Sun, Zhang and Qin.)

Background: Ankylosing spondylitis (AS) is a connective tissue disease that primarily affects spinal joints, peripheral joints, and paravertebral soft tissues, leading to joint stiffness and spinal deformity. Growing evidence has implicated gut microbiota in the regulation of AS, though the underlying mechanisms remain poorly understood., Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, the Cochrane Library, MEDLINE, Wanfang Data, China Science and Technology Journal Database (VIP), and China National Knowledge Internet (CNKI) databases from the time the databases were created until 30 July 2023. To evaluate changes in α-diversity and the abundance of certain microbiota families in AS, standardized mean difference (SMD) and 95% confidence interval (CI) calculations were made. Meta-analyses were performed using STATA 12.0 and the quality of the literature was assessed by following systematic review guidelines., Results: This systematic review and meta-analysis included 47 studies, providing insights into the gut microbiota composition in patients with AS compared to healthy controls (HCs). Our findings indicate a significant reduction in gut microbial diversity in patients with AS, as evidenced by a decrease in both richness and evenness. Specifically, the Shannon index showed a moderate decrease (SMD = -0.27, 95% CI: -0.49, -0.04; P < 0.001), suggesting a less diverse microbial ecosystem in patients with AS. The Chao1 index further confirmed this trend, with a larger effect size (SMD = -0.44, 95% CI: -0.80, -0.07; P < 0.001), indicating a lower species richness. The Simpson index also reflected a significant reduction in evenness (SMD = -0.30, 95% CI: -0.53, -0.06; P < 0.001). Additionally, patients with AS who received anti-rheumatic combination treatment exhibited a more pronounced reduction in α-diversity compared to untreated patients, highlighting the potential impact of this treatment on gut microbiota balance. In terms of specific microbial families, we observed a significant decrease in the abundance of Bifidobacterium (SMD = -0.42, 95% CI: -2.37, 1.52; P < 0.001), which is known for its beneficial effects on gut health. Conversely, an increase in the abundance of Bacteroidetes was noted (SMD = 0.42, 95% CI: -0.93, 1.76; P < 0.001), suggesting a possible shift in the gut microbiota composition that may be associated with AS pathophysiology., Conclusion: Our analysis revealed changes in α-diversity and the relative abundance of specific bacteria in AS. This suggests that targeting the gut microbiota could provide new therapeutic opportunities for treating AS., Systematic Review Registration: https://www.crd.york.ac.uk./PROSPERO/, identifier CRD42023450028., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Zhang, Qiao, Song, Shi, Wang, Wang and Zhang.)

The gut microbiota undergoes significant alterations in response to viral infections, particularly the novel SARS-CoV-2. As impaired gut microbiota can trigger numerous neurological disorders, we suggest that the long-term neurological symptoms of COVID-19 may be related to intestinal microbiota disorders in these patients. Thus, we have gathered available information on how the virus can affect the microbiota of gastrointestinal systems, both in the acute and the recovery phase of the disease, and described several mechanisms through which this gut dysbiosis can lead to long-term neurological disorders, such as Guillain-Barre syndrome, chronic fatigue, psychiatric disorders such as depression and anxiety, and even neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. These mechanisms may be mediated by inflammatory cytokines, as well as certain chemicals such as gastrointestinal hormones (e.g., CCK), neurotransmitters (e.g., 5-HT), etc. (e.g., short-chain fatty acids), and the autonomic nervous system. In addition to the direct influences of the virus, repurposed medications used for COVID-19 patients can also play a role in gut dysbiosis. In conclusion, although there are many dark spots in our current knowledge of the mechanism of COVID-19-related gut-brain axis disturbance, based on available evidence, we can hypothesize that these two phenomena are more than just a coincidence and highly recommend large-scale epidemiologic studies in the future.

Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.

The clinical value of the relationship between gastrointestinal microbiome imbalance and its corresponding interventions with kidney disease is emerging. This study describes the hotspots and evolution of gastrointestinal microbiome and kidney disease research over the past three decades by scientific collaboration networks and finally predicts future trends in the field through bibliometric analysis and visualization studies. CiteSpace was used to explore the original articles from January 1990 to August 2021 to visualize the knowledge network of journals, countries, institutions, authors, references, and keywords in this field. Publications were extracted from Web of Science Core Collection database using the terms “gastrointestinal microbiome” and “kidney disease” (and their synonyms in MeSH). A total of 2145 publications with 93880 references in 102 journals were included in the analyses. The number of studies combining gastrointestinal microbiomes with kidney diseases has increased significantly over the past two decades. The United States is the leading country in the number of documents, and the leading institution is the Cleveland Clinic. The most landmark articles in the field are on chronic renal failure, L-Carnitin, and cardiovascular disease. The pathogenesis of uremia toxin is an emerging trend in gastrointestinal microbiomes and kidney diseases. In addition, probiotic or synbiotic supplements have strong clinical value in adjusting abnormal intestinal symbiotic environments. This study demonstrates a growing understanding of the interaction between gut microbiota and kidney disease over time. Using microbial supplements to improve the living conditions of kidney disease patients is a promising and hot research focus. Based on publications extracted from the database, this study may provide clinicians and researchers with valuable information to identify potential collaborators and partner institutions and better predict their dynamic progression.

IntroductionThe Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) emerged in late December 2019. Considering the important role of gut microbiota in maturation, regulation, and induction of the immune system and subsequent inflammatory processes, it seems that evaluating the composition of gut microbiota in COVID-19 patients compared with healthy individuals may have potential value as a diagnostic and/or prognostic biomarker for the disease. Also, therapeutic interventions affecting gut microbial flora may open new horizons in the treatment of COVID-19 patients and accelerating their recovery.MethodsA systematic search was conducted for relevant studies published from December 2019 to December 2021 using Pubmed/Medline, Embase, and Scopus. Articles containing the following keywords in titles or abstracts were selected: “SARS-CoV-2” or “COVID-19” or “Coronavirus Disease 19” and “gastrointestinal microbes” or “dysbiosis” or “gut microbiota” or “gut bacteria” or “gut microbes” or “gastrointestinal microbiota”.ResultsOut of 1,668 studies, 22 articles fulfilled the inclusion criteria and a total of 1,255 confirmed COVID-19 patients were examined. All included studies showed a significant association between COVID-19 and gut microbiota dysbiosis. The most alteration in bacterial composition of COVID-19 patients was depletion in genera Ruminococcus, Alistipes, Eubacterium, Bifidobacterium, Faecalibacterium, Roseburia, Fusicathenibacter, and Blautia and enrichment of Eggerthella, Bacteroides, Actinomyces, Clostridium, Streptococcus, Rothia, and Collinsella. Also, some gut microbiome alterations were associated with COVID-19 severity and poor prognosis including the increment of Bacteroides, Parabacteroides, Clostridium, Bifidobacterium, Ruminococcus, Campylobacter, Rothia, Corynebacterium, Megasphaera, Enterococcus, and Aspergillus spp. and the decrement of Roseburia, Eubacterium, Lachnospira, Faecalibacterium, and the Firmicutes/Bacteroidetes ratio.ConclusionOur study showed a significant change of gut microbiome composition in COVID-19 patients compared with healthy individuals. This great extent of impact has proposed the gut microbiota as a potential diagnostic, prognostic, and therapeutic strategy for COVID-19. There is much evidence about this issue, and it is expected to be increased in near future.

Toxoplasma gondii ( T. gondii) is one of the most successful intracellular protozoa in that it can infect the majority of mammalian cell types during the acute phase of infection. Furthermore, it is able to establish a chronic infection for the host's entire lifespan by developing an encysted parasite form, primarily in the muscles and brain of the host, to avoid the host immune system. The infection affects one third of the world population and poses an increased risk for people with a suppressed immune system. Despite the dormant characteristics of chronic T. gondii infection, there is much evidence suggesting that this infection leads to specific behavior changes in both humans and rodents. Although numerous hypotheses have been put forth, the exact mechanisms underlying these behavior changes have yet to be understood. In recent years, several studies revealed a strong connection between the gut microbiome and the different organ systems that are affected in T. gondii infection. While it is widely studied and accepted that acute T. gondii infection can lead to a dramatic disruption of the host's normal, well-balanced microbial ecosystem (microbial dysbiosis), changes in the gut microbiome during the chronic stage of infection has not been well characterized. This review is intended to briefly inspect the different hypotheses that attempt to explain the behavior changes during T. gondii infection. Furthermore, this review proposes to consider the potential link between gut microbial dysbiosis, and behavior changes in T. gondii infection as a novel way to describe the underlying mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Prandovszky, Severance, Splan, Liu, Xiao and Yolken.)

Parkinson's disease (PD) is a neurodegenerative disorder that significantly impacts patients' quality of life. Recent evidence has highlighted a complex relationship between the gut microbiota (GM) and PD. Understanding this relationship is crucial for potentially targeting GM in PD treatment and expanding therapeutic options. This study aimed to comprehensively analyze the global landscape, trends, and research focus on GM and PD using bibliometric analysis. Utilizing publications from the Web of Science Core Collection (WsSCC), bibliometric tools such as the R package 'Bibliometrix,' VOS viewer, and CiteSpace software were employed to assess parameters like yearly publications, countries/regions, institutions, and authors. Research trends and hotspots were identified through keyword analysis. The results revealed 1,161 articles published between 2013-2023, with China leading in publications (n=352, 30.31% of total), while the United States had a higher influence (H-index=58). The University of California System was the top institution in terms of publications (n=35), with the National Natural Science Foundation of China funding the most projects (n=172). Keshavarzian A and Sampson TR were the authors with the highest publication and co-citation counts, respectively. The International Journal of Molecular Sciences had the most articles published (n=48). Keyword analysis identified parkinson's disease, gut microbiota, short-chain fatty acids, inflammation, and probiotics as main research topics. Biomarkers, ketogenic diet, and NF-κB were recent research hotspots and trends (2021-2023). The current study conducts an objective and comprehensive analysis of these publications, identifying trends and hotspots in the field of research. The findings offer valuable insights to scholars globally and in-vestigate potential therapeutic strategies for Parkinson's Disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Hao, Chen, Zhai, Pan, Zhou, Liu, Wu and Chen.)

The gut microbiota serves a crucial role in the development of host immunity. Immunocompromised patients are particularly vulnerable to dysbiosis not only by virtue of a defect in the immune system but also due to increased susceptibility to infection and multiple courses of antibiotic therapy. Fecal microbiota transplantation is by far the most effective option for restoring gastrointestinal homeostasis. However, it is contraindicated in patients with significant primary and secondary immunodeficiencies. This article presents the case of a 59-year-old patient with common variable immunodeficiency, after splenectomy at age 39 for primary immune thrombocytopenia, who manifested diarrhea of up to 10 stools per day accompanied by secondary malnutrition and cachexia. The patient was admitted to the hospital on multiple occasions due to this condition, with stool PCR tests confirming a HHV-5 ( Cytomegalovirus , CMV) infection. Following the administration of valganciclovir, the patient's complaints diminished, although, upon cessation of the drug, the symptoms recurred. In addition, the patient had an intestinal infection with C. difficile etiology. Given that the patient's therapeutic options had been exhausted, after obtaining informed consent from the patient and approval from the bioethics committee to conduct a medical experiment, treatment of diarrhea was undertaken by fecal microbiota transplantation with the certified preparation Mbiotix HBI from the Human Biome Institute. The patient underwent two transplants, with a one-week interval between them. The initial procedure was performed using the endoscopic method, while the subsequent was conducted using the capsule method. Following the administration of the applied treatment, the patient's symptoms were successfully alleviated, and no adverse effects were observed. A microbiological analysis of the intestinal microbiota was conducted prior to and following transplantation via next-generation sequencing (NGS). No recurrence of symptoms was observed during the two-year follow-up period. To the best of our knowledge, this is the first fecal microbiota transplantation in an adult patient with primary and secondary immunodeficiency., Competing Interests: The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Napiórkowska-Baran, Biliński, Pujanek, Hałakuc, Pietryga, Szymczak, Deptuła, Rosada and Bartuzi.)

Sepsis, a disease with high incidence, mortality, and treatment costs, has a complex interaction with the gut microbiota. With advances in high-throughput sequencing technology, the relationship between sepsis and intestinal dysbiosis has become a new research focus. However, owing to the intricate interplay between critical illness and clinical interventions, it is challenging to establish a causal relationship between sepsis and intestinal microbiota imbalance. In this review, the correlation between intestinal microecology and sepsis was summarized, and new therapies for sepsis intervention based on microecological target therapy were proposed, and the shortcomings of bacterial selection and application timing in clinical practice were addressed. In conclusion, current studies on metabolomics, genomics and other aspects aimed at continuously discovering potential probiotics are all providing theoretical basis for restoring intestinal flora homeostasis for subsequent treatment of sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tao, Wang, Liu, Liu, Zhang, Zhou, Li and Zhu.)

Infertility is a disease of impaired fertility. With socioeconomic development, changes in human lifestyles, and increased environmental pollution, the problem of low human fertility has become increasingly prominent. The incidence of global infertility is increasing every year. Many factors lead to infertility, and common female factors include tubal factors, ovulation disorders, endometriosis, and immune factors. The gut microbiota is involved in many physiological processes, such as nutrient absorption, intestinal mucosal growth, glycolipid metabolism, and immune system regulation. An altered gut flora is associated with female infertility disorders such as polycystic ovary syndrome (PCOS), endometriosis (EMs), and premature ovarian failure (POF). Dysbiosis of the gut microbiota directly or indirectly contributes to the development of female infertility disorders, which also affect the homeostasis of the gut microbiota. Identifying the etiology and pathogenesis of infertility in patients is the focus of reproductive medicine physicians. We studied the developmental mechanism between the gut microbiota and PCOS, EMs, and POF from a new perspective, providing new ideas for diagnosing and treating female infertility diseases and specific reference values for eugenics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Wang, Zheng, Ma, Zhao and Xu.)

Background and Purpose: While there is evidence that gut microbiota (GM) and blood metabolites are associated with ovarian cancer (OC), the precise mechanisms underlying this relationship are still unclear. This study used Mendelian randomization (MR) to elucidate the causal connections between GM, blood metabolite biomarkers, and OC., Methods: In this study, we leveraged summary data for GM (5,959 individuals with genotype-matched GM), blood metabolites (233 circulating metabolic traits with 136,016 participants), and OC (63,702 participants with 23,564 cases and 40,138 controls) from genome-wide association studies (GWASs). We performed MR analysis to explore the causal relationship between GM and OC. Further, we harnessed univariable MR (UVMR) analysis to evaluate the causal associations between GM and circulating metabolites. Finally, we employed a two-step approach based on multivariable MR (MVMR) to evaluate the total genetic prediction effect of metabolites mediating the GM on the risk of OC to discover a potential causal relationship., Results: In the MR analysis, 24 gut bacteria were causally associated with the pathogenesis of OC, including 10 gut bacteria ( Dorea phocaeense , Succinivibrionaceae , Raoultella , Phascolarctobacterium sp003150755 , Paenibacillus J , NK4A144 , K10 , UCG-010 sp003150215 , Pseudomonas aeruginosa , and Planococcaceae ) that were risk factors, and 14 gut bacteria ( CAG-177 sp002438685 , GCA-900066135 sp900066135 , Enorma massiliensis , Odoribacter laneus , Ruminococcus E sp003521625 , Streptococcus sanguinis , Turicibacter sp001543345 , Bacillus velezensis , CAG-977 , CyanobacteriaStaphylococcus A fleurettii , Caloranaerobacteraceae , RUG472 sp900319345 , and CAG-269 sp001915995 ) that were protective factors. The UVMR analysis showed that these 24 positive gut bacteria were causally related to lipoproteins, lipids, and amino acids. According to the MVMR analysis, Enorma massiliensis could reduce the risk of OC by raising the total cholesterol to total lipids ratio in large low-density lipoprotein (LDL) and cholesteryl esters to total lipids ratio in intermediate-density lipoprotein (IDL). Turicibacter sp001543345 , however, could reduce the risk of OC by lowering free cholesterol in small high-density lipoprotein (HDL) and increasing the ratios of saturated fatty acids to total fatty acids, total cholesterol to total lipids ratio in very small very-low-density lipoprotein (VLDL), and cholesteryl esters to total lipids ratio in very small VLDL., Conclusion: The current MR study provides evidence that genetically predicted blood metabolites can mediate relationships between GM and OC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Cao, Liu, Sun, Wang and Guo.)

Background: There is a crosstalk between gut microbiota and radiotherapy. The aim of this study is to use bibliometric analysis to explore the research status and development trends of research on gut microbiota and radiotherapy., Methods: A literature search regarding publications on gut microbiota and radiotherapy from 2004 to 2023 was retrieved. CiteSpace and VOSviewer were used to conduct the bibliometric analysis. The growth rate of publications, leading countries and institutions, preferred journals, top authors and co-cited authors, top co-cited references, keywords and citation were analyzed in this study., Results: A total of 2821 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2017. The USA and China had the most publications and made great contributions to this field. The Chinese Academy of Sciences stood out as the institution with the highest number of publications, followed by the Chinese Academy of Medical Sciences & Peking Union Medical College. The most influential authors were Fan Saijun and Li Yuan. PLoS One had the most publications and the most total citations. Highly cited papers and high-frequency keywords illustrated the current status and trends. Furthermore, analysis of keyword with burst revealed that immunotherapy , acid , intestinal barrier, therapy , immunotherapy , fecal microbiota transplantation , etc, are at the forefront of research in this area., Conclusion: This study provides an overview of research on gut microbiota and radiotherapy, highlighting influential contributors, impactful publications, and emerging trends. Our finding suggests avenues for further exploration to improve clinical outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Yuan, Gao, Wu, Ren, Yu, Li and Wei.)

Short-chain fatty acids (SCFAs), a subset of organic fatty acids with carbon chains ranging from one to six atoms in length, encompass acetate, propionate, and butyrate. These compounds are the endproducts of dietary fiber fermentation, primarily catalyzed by the glycolysis and pentose phosphate pathways within the gut microbiota. SCFAs act as pivotal energy substrates and signaling molecules in the realm of animal nutrition, exerting a profound influence on the intestinal, immune system, and intestinal barrier functions. Specifically, they contibute to 60-70% of the total energy requirements in ruminants and 10-25% in monogastric animals. SCFAs have demonstrated the capability to effectively modulate intestinal pH, optimize the absorption of mineral elements, and impede pathogen invasion. Moreover, they enhance the expression of proteins associated with intestinal tight junctions and stimulate mucus production, thereby refining intestinal tissue morphology and preserving the integrity of the intestinal structure. Notably, SCFAs also exert anti-inflammatory properties, mitigating inflammation within the intestinal epithelium and strengthening the intestinal barrier's defensive capabilities. The present review endeavors to synthesize recent findings regarding the role of SCFAs as crucial signaling intermediaries between the metabolic activities of gut microbiota and the status of porcine cells. It also provides a comprehensive overview of the current literature on SCFAs' impact on immune responses within the porcine intestinal mucosa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Lu, Wang, Yu, He and Dong.)

Background: The infant gut microbiome's establishment is pivotal for health and immune development. Understanding it unveils insights into growth, development, and maternal microbial interactions. Research often emphasizes gut bacteria, neglecting the phageome., Methods: To investigate the influence of geographic or maternal factors (mode of delivery, mode of breastfeeding, gestational diabetes mellitus) on the gut microbiota and phages of newborns, we collected fecal samples from 34 pairs of mothers and their infants within 24 hours of delivery from three regions (9 pairs from Enshi, 7 pairs from Hohhot, and 18 pairs from Hulunbuir) using sterile containers. Gut microbiota analysis by Shotgun sequencing was subsequently performed., Results: Our results showed that geographic location affects maternal gut microbiology ( P < 0.05), while the effect on infant gut microbiology was not significant ( P = 0.184). Among the maternal factors, mode of delivery had a significant ( P < 0.05) effect on the newborn. Specific bacteria (e.g., Bacteroides , Escherichia spp., Phocaeicola vulgatus , Escherichia coli , Staphylococcus hominis , Veillonella spp.), predicted active metabolites, and bacteriophage vOTUs varied with delivery mode. Phocaeicola vulgatus significantly correlated with some metabolites and bacteriophages in the early infant gut ( P < 0.05). In the GD group, a strong negative correlation of phage diversity between mother and infants was observed ( R = -0.58, P =0.04)., Conclusion: In conclusion, neonatal early gut microbiome (including bacteria and bacteriophages) colonization is profoundly affected by the mode of delivery, and maternal gestational diabetes mellitus. The key bacteria may interact with bacteriophages to influence the levels of specific metabolites. Our study provides new evidence for the study of the infant microbiome, fills a gap in the analysis of the infant gut microbiota regarding the virome, and emphasizes the importance of maternal health for the infant initial gut virome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Shi, Liu, Ma, Jin, Zhao and Sun.)

Hypertensive disorders of pregnancy (HDP) are severe complications of pregnancy with high morbidity and are a major cause of increased maternal and infant morbidity and mortality. Currently, there is a lack of effective early diagnostic indicators and safe and effective preventive strategies for HDP in clinical practice, except for monitoring maternal blood pressure levels, the degree of proteinuria, organ involvement and fetal conditions. The intestinal microbiota consists of the gut flora and intestinal environment, which is the largest microecosystem of the human body and participates in material and energy metabolism, gene expression regulation, immunity regulation, and other functions. During pregnancy, due to changes in hormone levels and altered immune function, the intestinal microecological balance is affected, triggering HDP. A dysregulated intestinal microenvironment influences the composition and distribution of the gut flora and changes the intestinal barrier, driving beneficial or harmful bacterial metabolites and inflammatory responses to participate in the development of HDP and promote its malignant development. When the gut flora is dysbiotic and affects blood pressure, supplementation with probiotics and dietary fiber can be used to intervene. In this review, the interaction between the intestinal microbiota and HDP was investigated to explore the feasibility of the gut flora as a novel biomarker of HDP and to provide a new strategy and basis for the prevention and treatment of clinical HDP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Wang, Zheng, Meng, Ma, Zhao and Xu.)

Objective: This study aims to investigate the pathogenesis of hyperglycemia and its associated vasculopathy using multiomics analyses in diabetes and impaired glucose tolerance, and validate the mechanism using the cell experiments., Methods: In this study, we conducted a comprehensive analysis of the metagenomic sequencing data of diabetes to explore the key genera related to its occurrence. Subsequently, participants diagnosed with impaired glucose tolerance (IGT), and healthy subjects, were recruited for fecal and blood sample collection. The dysbiosis of the gut microbiota (GM) and its associated metabolites were analyzed using 16S rDNA sequencing and liquid chromatograph mass spectrometry, respectively. The regulation of gene and protein expression was evaluated through mRNA sequencing and data-independent acquisition technology, respectively. The specific mechanism by which GM dysbiosis affects hyperglycemia and its related vasculopathy was investigated using real-time qPCR, Western blotting, and enzyme-linked immunosorbent assay techniques in HepG2 cells and neutrophils., Results: Based on the published data, the key alterable genera in the GM associated with diabetes were identified as Blautia , Lactobacillus , Bacteroides , Prevotella , Faecalibacterium , Bifidobacterium , Ruminococcus , Clostridium , and Lachnoclostridium . The related metabolic pathways were identified as cholate degradation and L-histidine biosynthesis. Noteworthy, Blautia and Faecalibacterium displayed similar alterations in patients with IGT compared to those observed in patients with diabetes, and the GM metabolites, tauroursodeoxycholic acid (TUDCA) and carnosine (CARN, a downstream metabolite of histidine and alanine) were both found to be decreased, which in turn regulated the expression of proteins in plasma and mRNAs in neutrophils. Subsequent experiments focused on insulin-like growth factor-binding protein 3 and interleukin-6 due to their impact on blood glucose regulation and associated vascular inflammation. Both proteins were found to be suppressed by TUDCA and CARN in HepG2 cells and neutrophils., Conclusion: Dysbiosis of the GM occurred throughout the entire progression from IGT to diabetes, characterized by an increase in Blautia and a decrease in Faecalibacterium , leading to reduced levels of TUDCA and CARN, which alleviated their inhibition on the expression of insulin-like growth factor-binding protein 3 and interleukin-6, contributing to the development of hyperglycemia and associated vasculopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhen, Zhang, Li, Zhou, Cai, Huang and Xu.)

Gouty arthritis (GA), a metabolic and immunologic disease, primarily affects joints. Dysbiosis of intestinal flora is an important cause of GA. The metabolic disorders of intestinal flora leading to GA and immune disorders might play an important role in patients with hyperuricemia and established GA. However, the exact mechanisms, through which the dysbiosis of intestinal flora causes the development of GA, are not fully understood yet. Moreover, several therapies commonly used to treat GA might alter the intestinal flora, suggesting that modulation of the intestinal flora might help prevent or treat GA. Therefore, a better understanding of the changes in the intestinal flora of GA patients might facilitate the discovery of new diagnostic and therapeutic approaches. The current review article discusses the effects of intestinal flora dysbiosis on the pathogenesis of GA and the cross-regulatory effects between gut flora and drugs for treating GA. This article also highlights the modulatory effects of gut flora by traditional Chinese medicine (TCM) to lower uric acid levels and relieve joint pain as well as provides a summary and outlook, which might help guide future research efforts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiao, Zhang, Xi, Li, Wei, Shen, Wang, Qin, Xie and Li.)

Background: Psoriasis is one of the most common autoimmune skin diseases. Increasing evidence shows that alterations in the diversity and function of microbiota can participate in the pathogenesis of psoriasis through various pathways and mechanisms., Objective: To review the connection between microbial changes and psoriasis, how microbial-targeted therapy can be used to treat psoriasis, as well as the potential of prebiotics, probiotics, synbiotics, fecal microbiota transplantation, diet, and Traditional Chinese Medicine as supplementary and adjunctive therapies., Methods: Literature related to the relationship between psoriasis and gut microbiota was searched in PubMed and CNKI., Results: Adjunct therapies such as dietary interventions, traditional Chinese medicine, and probiotics can enhance gut microbiota abundance and diversity in patients with psoriasis. These therapies stimulate immune mediators including IL-23, IL-17, IL-22, and modulate gamma interferon (IFN-γ) along with the NF-kB pathway, thereby suppressing the release of pro-inflammatory cytokines and ameliorating systemic inflammatory conditions., Conclusion: This article discusses the direction of future research and clinical treatment of psoriasis from the perspective of intestinal microbiota and the mechanism of traditional Chinese medicine, so as to provide clinicians with more comprehensive diagnosis and treatment options and bring greater hope to patients with psoriasis., Competing Interests: The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zou, Zou, Gao and Zhao.)

The human gut microbiome (GM) impacts various physiological processes and can lead to pathological conditions and even carcinogenesis if homeostasis is disrupted. Recent studies have indicated a connection between the GM and prostatic disease. However, the underlying mechanisms are still unclear. This review aims to provide a summary of the existing information regarding the connection between the GM and various prostatic conditions such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Furthermore, the review aims to identify possible pathogenic mechanisms and suggest potential ways of targeting GM to prevent and treat prostatic disease. Due to the complexity of the mechanism between GM and prostatic diseases, additional research is required to comprehend the association between the two. This will lead to more effective treatment options for prostatic disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Zhang, Wang, Wang, Shi, Wu, Du, Zhang, Gou, Zhou and Wang.)

Background: Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy., Methods: A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the "Up to standard" (US) group and the "Below standard" (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites., Results: A total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium&#95;coprostanoligenes and g-Papillibacter , while the characteristic flora of the BS group were o-C0119 , g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-β-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism., Conclusions: The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Hu, zhang, Hu, Zhang, Zhang, Yu, Liu, Wang, Lin, Gong, Zhang, Li and Li.)

Background: Aberrant activation of the classic renin-angiotensin system (RAS) and intestinal micro dysbiosis adversely affect insulin resistance (IR), dyslipidemia, and other metabolic syndrome markers. However, the action of angiotensin-converting enzyme 2 (ACE2) and gut health in systemic homeostasis vary, and their interaction is not completely understood., Methods: We adopted a combinatory approach of metabolomics and fecal 16S rRNA analysis to investigate gut microbiota and metabolite in two different mouse models, ACE2 knockout ( ACE2 KO) mice and the ACE2-overexpressing obese mice., Results: 16S rRNA gene sequencing revealed that ACE2 influences microbial community composition and function, and ACE2 KO mice had increased Deferribacteres , Alcaligenaceae , Parasutterella , Catenibacterium , and Anaerotruncus , with decreased short-chain fatty acid (SCFA)-producing bacteria ( Marvinbryantia and Alistipes ). In contrast, ACE2-overexpressed mice exhibited increased anti-inflammatory probiotic ( Oscillospiraceae , Marinifilaceae , and Bifidobacteriaceae ) and SCFA-producing microbes ( Rikenellaceae, Muribaculaceae , Ruminococcaceae , Odoribacter , and Alistipes ) and decreased Firmicutes/Bacteroidetes , Lactobacillaceae , Erysipelotrichaceae , and Lachnospiraceae . Metabolome analysis indicated differential metabolites in ACE2 KO and ACE2-overexpression mice, especially the glucolipid metabolism-related compounds. Furthermore, correlation analysis between gut microbiota and metabolites showed a dynamic mutual influence affecting host health., Conclusion: Our study confirms for the first time a significant association between ACE2 status and gut microbiome and metabolome profiles, providing a novel mechanism for the positive effect of ACE2 on energy homeostasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Ji and Cao.)

Introduction: Extensive research efforts have been dedicated to elucidating the intricate pathways by which gastrointestinal microbiota and their metabolites exert influence on the processes of bone formation. Nonetheless, a notable gap exists in the literature concerning a bibliometric analysis of research trends at the nexus of gastrointestinal microbiota and bone metabolism., Methods: To address this scholarly void, the present study employs a suite of bibliometric tools including online platforms, CiteSpace and VOSviewer to scrutinize the pertinent literature in the realm of gastrointestinal microbiota and bone metabolism., Results and Discussion: Examination of the temporal distribution of publications spanning from 2000 to 2023 reveals a discernible upward trajectory in research output, characterized by an average annual growth rate of 19.2%. Notably, China and the United States emerge as primary contributors. Predominant among contributing institutions are Emory University, Harvard University, and the University of California. Pacifici R from Emory University contributed the most research with 15 publications. In the realm of academic journals, Nutrients emerges as the foremost publisher, followed closely by Frontiers in Microbiology and PLOS One . And PLOS One attains the highest average citations of 32.48. Analysis of highly cited papers underscores a burgeoning interest in the therapeutic potential of probiotics or probiotic blends in modulating bone metabolism by augmenting host immune responses. Notably, significant research attention has coalesced around the therapeutic interventions of probiotics, particularly Lactobacillus reuteri , in osteoporosis, as well as the role of gastrointestinal microbiota in the etiology and progression of osteoarthritis. Keyword analysis reveals prevalent terms including gut microbiota, osteoporosis, bone density, probiotics, inflammation, SCFAs, metabolism, osteoarthritis, calcium absorption, obesity, double-blind, prebiotics, mechanisms, postmenopausal women, supplementation, risk factors, oxidative stress, and immune system. Future research endeavors warrant a nuanced exploration of topics such as inflammation, obesity, SCFAs, postmenopausal osteoporosis, skeletal muscle, oxidative stress, double-blind trials, and pathogenic mechanisms. In summary, this study presents a comprehensive bibliometric analysis of global research on the interplay between gastrointestinal microbiota and bone metabolism, offering valuable insights for scholars, particularly nascent researchers, embarking on analogous investigations within this domain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Sun, Guo and Li.)

Acupuncture, an important green and side effect-free therapy in traditional Chinese medicine, is widely use both domestically and internationally. Acupuncture can interact with the gut microbiota and influence various diseases, including metabolic diseases, gastrointestinal diseases, mental disorders, nervous system diseases, and other diseases. This review presents a thorough analysis of these interactions and their impacts and examines the alterations in the gut microbiota and the potential clinical outcomes following acupuncture intervention to establish a basis for the future utilization of acupuncture in clinical treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Luo, Li and Zhu.)

Breast cancer (BrCa) is the most prevalent malignant tumor in women and one of the leading causes of female mortality. Its occurrence and progression are influenced by various factors, including genetics, environment, lifestyle, and hormones. In recent years, the gut microbiota has been identified as a significant factor affecting BrCa. The gut microbiota refers to the collective population of various microorganisms in the human gastrointestinal tract. Gut microbiota is closely associated with human health and disease development, participating in crucial physiological functions such as digestion, metabolism, immune response, and neural regulation. It has been found to influence the occurrence and treatment of BrCa through a variety of mechanisms. This article aims to review the immunomodulatory role of the gut microbiota in the development and treatment of BrCa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xue, Li and Huang.)

Introduction: In this study, the seasonal differences in the intestinal microbiota of Chinese mitten crab ( Eriocheir sinensis ) larvae were investigated at different sites in the intertidal zone of the Yangtze River Estuary., Methods: 16S rRNA high-throughput sequencing technology was used to compare and analyze the microbial community structure in the intestines of juvenile crab from different seasons., Results: The results showed that the main microbial phyla in all seasons and sites were Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria, which accounted for 97.1% of the total microbiota. Composition analysis revealed that the relative abundance of Proteobacteria decreased from summer to winter at each station, whereas Bacteroidetes showed the opposite trend. Alpha diversity analysis showed that species richness increased from summer to winter at the upstream site ( P < 0.05), but decreased at the downstream site ( P < 0.05), with no significant differences observed in other comparisons. Biomarker species analysis showed that juvenile crab exhibited a more specialized microbial community in summer compared with autumn and winter. Co-occurrence network analysis revealed that microbial interaction network complexity was lower in autumn compared with summer and autumn. Functional prediction analysis showed that the microbial community only exhibited seasonal differences in amino acid biosynthesis, cofactor, prosthetic group, electron carrier, and vitamin biosynthesis, aromatic compound degradation, nucleotide and nucleoside degradation, and tricarboxylic acid cycle pathways., Discussion: The results indicated that the microbiota did not significantly differ among sites, and seasonal variation was a main factor influencing the differences in intestinal microbiota of Chinese mitten juvenile crab. Moreover, the microbial community was more complex in summer compared with autumn and winter., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qin, Wang, Wu, Sun and Zhao.)

Introduction: Ulcerative colitis is an inflammatory disorder characterized by chronic inflammation in the gastrointestinal tract, mainly in the colon and rectum. Although the precise etiology of ulcerative colitis remains unclear, recent research has underscored the significant role of the microbiome in its development and progression., Methods: The aim of this study was to establish a relationship between the levels of specific gut bacterial species and disease relapse in ulcerative colitis. For this study, we recruited 105 ulcerative colitis patients in remission and collected clinical data, blood, and stool samples. Akkermansia muciniphila and Parabacteroides distasonis levels were quantified in the stool samples of ulcerative colitis patients. Binary logistic regression was applied to collected data to predict disease remission., Results: The median time in remission in this cohort was four years. A predictive model incorporating demographic information, clinical data, and the levels of Akkermansia muciniphila and Parabacteroides distasonis was developed to understand remission patterns., Discussion: Our findings revealed a negative correlation between the levels of these two microorganisms and the duration of remission. These findings highlight the importance of the gut microbiota in ulcerative colitis for disease prognosis and for personalized treatments based on microbiome interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mendes-Frias, Moreira, Vieira, Gaifem, Costa, Lopes and Silvestre.)

Background: Despite mounting evidence of gut-brain involvement in psychiatric conditions, functional data remain limited, and analyses of other microbial niches, such as the vaginal microbiota, are lacking in relation to mental health. This aim of this study was to investigate if the connections between the gut microbiome and mental health observed in populations with a clinical diagnosis of mental illness extend to healthy women experiencing stress and depressive symptoms. Additionally, this study examined the functional pathways of the gut microbiota according to the levels of psychological symptoms. Furthermore, the study aimed to explore potential correlations between the vaginal microbiome and mental health parameters in young women without psychiatric diagnoses., Methods: In this cross-sectional study, 160 healthy Danish women (aged 18-40 years) filled out questionnaires with validated scales measuring symptoms of stress and depression and frequency of dietary intake. Fecal and vaginal microbiota samples were collected at the beginning of the menstrual cycle and vaginal samples were also collected at cycle day 8-12 and 18-22. Shotgun metagenomic profiling of the gut and vaginal microbiome was performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for functional profiling and 56 Gut Brain Modules were analyzed in the fecal samples., Results: The relative abundance in the gut of the genera Escherichia , Parabacteroides , and Shigella was higher in women with elevated depressive symptoms. Women with high perceived stress showed a tendency of increased abundance of Escherichia , Shigella , and Blautia . Amongst others, the potentially pathogenic genera, Escherichia and Shigella correlate with alterations in the neuroactive pathways such as the glutamatergic, GABAeric, dopaminergic, and Kynurenine pathways. Vaginosis symptoms were more prevalent in women reporting high levels of stress and depressive symptoms., Conclusions: The findings of this study support the concept of a microbiota-associated effect on the neuroactive pathways even in healthy young women. This suggest, that targeting the gut microbiome could be a promising approach for future psychiatric interventions., Competing Interests: An unrestricted research grant from Ferring Pharmaceuticals enabled the clinical infrastructure, and sampling as well as the analyses at the Centre for Translational Microbiome Research. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2024 Bashir, Hugerth, Krog, Prast-Nielsen, Edfeldt, Boulund, Schacht, Tetens, Engstrand, Schuppe-Koistinen, Fransson and Nielsen.)

Several lines of evidence suggest that the intestinal microbiota plays crucial roles in infant development, and that it is highly influenced by extrinsic and intrinsic factors. Prebiotic-containing infant formula may increase gastrointestinal tolerance and improve commensal microbiota composition. However, it remains unknown whether supplementation of milk-formulas with prebiotics and 1,3-olein-2-palmitin (OPO) can achieve feeding outcomes similar to those of breastfeeding. In the present study, we investigated the effects of two kinds of infant formula with different additives on the overall diversity and composition of the fecal microbiota, to determine which was closer to breastfeeding. A total of 108 infants were enrolled, including breastfeeding (n=59) and formula feeding group (n=49). The formula feeding infants were prospectively randomly divided into a standard formula group (n=18), and a supplemented formula group(n=31). The fecal samples were collected at 4 months after intervention. Fecal microbiota analysis targeting the V4 region of the 16S rRNA gene was performed using MiSeq sequencing. The overall bacterial diversity and composition, key functional bacteria, and predictive functional profiles in the two different formula groups were compared with breastfeeding group. We found that the alpha diversity of the gut microbiota was not significantly different between the OPO and breastfeeding groups with Chaos 1 index (p=0.346). The relative abundances of Enhydrobacter and Akkermansia in the OPO group were more similar to those of the breastfeeding group than to those of the standard formula group. The gut microbiota metabolism function prediction analysis showed that the supplemented formula group was similar to the breastfeeding group in terms of ureolysis (p=0.297). These findings suggest that, when formula supplemented with prebiotics and OPO was given, the overall bacterial diversity and parts of the composition of the fecal microbiota would be similar to that of breastfeeding infants.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction: Rumen acidosis is one of the most common diseases in beef cattle. It severely affects the normal development of calves and poses a significant threat to the farming industry. However, the influence of rumen acidosis on the gut microbiota and serum metabolites of calves is currently unclear., Objective: The aim of this study is to investigate the changes in the gut microbiota and serum metabolites in calves after rumen acidosis and analyse the correlation., Methods: Eight calves were selected as the rumen acidosis group, and eight health calves were selected as the healthy group. The faecal gut microbiota and serum metabolites of calves were detected respectively using 16S rDNA high-throughput sequencing and non-target metabolomics. The correlation between gut microbiota and serum metabolites was analyzed by Spearman correlation analysis., Results: Differential analysis of the diversity and composition of gut microbiota between eight male healthy (Health) and eight male rumen acidosis (Disease) calves revealed that rumen acidosis increased the abundance of the gut microbiota in calves. At the phylum level, compared to the Healthy group, the relative abundance of Proteobacteria in the Disease group significantly decreased ( P <0.05), while the relative abundance of Desulfobacterota significantly increased in the Disease group ( P <0.05). At the genus level, compared to the Disease group, the relative abundance of Alloprevotella , Muribaculaceae , Succinivibrio , Prevotella , Agathobacter and Parabacteroides significantly increased in the Healthy group ( P <0.05), while the relative abundance of Christensenellaceae&#95;R-7 and Monoglobus significantly decreased in the Healthy group ( P <0.05). Differential analysis results showed the Healthy group had 23 genera with higher abundance, while the Disease group had 47 genera with higher abundance. Serum metabolomics results revealed the differential metabolites associated with rumen acidosis, including nicotinamide, niacin, L-glutamic acid and carnosine, were mainly enriched in the nicotinate and nicotinamide pathway and the histidine pathway., Conclusion: The occurrence of rumen acidosis can induce changes in the gut microbiota of calves, with a significant increase of the Christensenellaceae&#95;R-7 genus and a significant decrease of Prevotella and Succinivibrio genera. In addition, the occurrence of rumen acidosis can also induce changes in serum metabolites including niacin, niacinamide, L-glutamine, and carnosine, which may serve as the diagnostic biomarkers of rumen acidosis of calves., Competing Interests: Author XZ was employed by Zhangye Wanhe Grass Livestock Industry Science and Technology Development Co., Ltd. The remaining authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Ji, Yang, Zhu and Wu.)

Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the bacterial population of the small intestine due to an imbalance between the amount of bacteria and the intestinal barrier. Pediatric SIBO presents with a wide spectrum of symptoms, ranging from mild gastrointestinal complaints to malabsorption or malnutrition. Breath tests are commonly used as noninvasive diagnostic tools for SIBO, but a standardized methodology is currently unavailable. Intestinal flora produces methane which slows intestinal transit and increases the contractile activity of small intestine. Emerging literature suggests a correlation between overgrowth of methanogenic bacteria in the intestines and constipation. Treatment of SIBO involves administration of antibacterial therapy in addition to management of underlying conditions and optimal dietary adjustments. However, research on antibiotic treatment for pediatric patients with constipation and SIBO is limited and has yielded conflicting results. In the current review, we summarize the state-of-the-art of the field and discuss previous treatment attempts and currently used regimens for SIBO patients with constipation, with a focus on pediatric populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mares, Săsăran and Mărginean.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The Cecum is a key site for cellulose digestion in nutrient metabolism of intestine, but its mechanisms of microbial and gene interactions has not been fully elucidated during pathogenesis of obesity. Therefore, the cecum tissues of the New Zealand rabbits and their contents between the high-fat diet-induced group (Ob) and control group (Co) were collected and analyzed using multi-omics. The metagenomic analysis indicated that the relative abundances of Corallococcus&#95;sp.&#95;CAG:1435 and Flavobacteriales bacterium species were significantly lower, while those of Akkermansia glycaniphila , Clostridium&#95;sp.&#95;CAG:793 , Mycoplasma&#95;sp.&#95;CAG:776 , Mycoplasma&#95;sp.&#95;CAG:472 , Clostridium&#95;sp.&#95;CAG:609 , Akkermansia&#95;sp.&#95;KLE1605 , Clostridium&#95;sp.&#95;CAG:508 , and Firmicutes&#95;bacterium&#95;CAG:460 species were significantly higher in the Ob as compared to those in Co. Transcriptomic sequencing results showed that the differentially upregulated genes were mainly enriched in pathways, including calcium signaling pathway, PI3K-Akt signaling pathway, and Wnt signaling pathway, while the differentially downregulated genes were mainly enriched in pathways of NF-kappaB signaling pathway and T cell receptor signaling pathway. The comparative analysis of metabolites showed that the glycine, serine, and threonine metabolism and cysteine and methionine metabolism were the important metabolic pathways between the two groups. The combined analysis showed that CAMK1 , IGFBP6 , and IGFBP4 genes were highly correlated with Clostridium&#95;sp.&#95;CAG:793 , and Akkermansia&#95;glycaniphila species. Thus, the preliminary study elucidated the microbial and gene interactions in cecum of obese rabbit and provided a basis for further studies in intestinal intervention for human obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Qi, Wang, He, Li, Cen and Wei.)

Silkworm ( Bombyx mori ) larvae are expected to be useful as an ingredient in entomophagy. They are full of nutrients, including indigestible proteins; however, there have been few studies on the effects of the consumption of the entire body of silkworms on the intestinal microflora. We prepared a customized diet containing silkworm larval powder (SLP), and investigated the effects of ad libitum feeding of the SLP diet on the intestinal microbiota and the amount of short-chain fatty acids (SCFAs) in mice. We found that the diversity of the cecal and fecal microbiota increased in the mice fed the SLP diet (SLP group), and that the composition of their intestinal microbiota differed from that of the control mice. Furthermore, a genus-level microbiota analysis showed that in the SLP group, the proportions of Alistipes , Lachnospiraceae A2, and RF39, which are associated with the prevention of obesity, were significantly increased, while the proportions of Helicobacter and Anaerotruncus , which are associated with obesity, were significantly decreased. Additionally, the level of butyrate was increased in the SLP group, and Clostridia UCG 014 and Lachnospiraceae FCS020 were found to be associated with the level of butyrate, one of the major SCFAs. These findings indicated that silkworm powder may be useful as an insect food that might also improve obesity., Competing Interests: HU is an employee of Morus Inc. The other authors declare that they have no commercial or financial relationships that could be construed to be a potential conflict of interest., (Copyright © 2024 Murakami, Yamaguchi, Namai, Sato, Yamazaki, Uehara, Fujii, Tochio, Shiomi and Shimosato.)

Introduction: In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles., Methods: Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators., Results: Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA., Conclusion: The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhang, Guo, Li, Wang and Zhang.)

In recent years, a growing body of research has confirmed that the gut microbiota plays a major role in the maintenance of human health and disease. A gut microbiota imbalance can lead to the development of many diseases, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome, endometriosis, and cancer. Short-chain fatty acids are metabolites of specific intestinal bacteria and are crucial for maintaining intestinal homeostasis and regulating metabolism and immunity. Endometriosis is the result of cell proliferation, escape from immune surveillance, and invasive metastasis. There is a strong correlation between the anti-proliferative and anti-inflammatory effects of short-chain fatty acids produced by gut microbes and the development of endometriosis. Given that the mechanism of action of gut microbiota and Short-chain fatty acids in endometriosis remain unclear, this paper aims to provide a comprehensive review of the complex interactions between intestinal flora, short-chain fatty acids and endometriosis. In addition, we explored potential microbial-based treatment strategies for endometriosis, providing new insights into the future development of diagnostic tests and prevention and treatment methods for endometriosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Peng, Tian, Shi, Ma, Shi, Qi, Zhao and Guan.)

In recent years, there has been increasing interest in studying gut microbiome-derived hydrolases in relation to oral drug metabolism, particularly focusing on natural product drugs. Despite the significance of natural product drugs in the field of oral medications, there is a lack of research on the regulatory interplay between gut microbiome-derived hydrolases and these drugs. This review delves into the interaction between intestinal microbiome-derived hydrolases and natural product drugs metabolism from three key perspectives. Firstly, it examines the impact of glycoside hydrolases, amide hydrolases, carboxylesterase, bile salt hydrolases, and epoxide hydrolase on the structure of natural products. Secondly, it explores how natural product drugs influence microbiome-derived hydrolases. Lastly, it analyzes the impact of interactions between hydrolases and natural products on disease development and the challenges in developing microbial-derived enzymes. The overarching goal of this review is to lay a solid theoretical foundation for the advancement of research and development in new natural product drugs and personalized treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Liu, Zhang, Wang, Cao and Liu.)

Introduction: Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women., Methods: In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis., Results: The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene., Discussion: Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Wang, Yu, Qi, Li, Nan, Wang, Luo, Hua and Wang.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.