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Hepatitis viral infection can cause severe complications, even mortality in pregnant women and their offspring. Multiple studies have shown that vertical transmission can cause viral hepatitis infections in newborns, especially in hepatitis B, C, and E. Screening for hepatitis viral infection in pregnant women is essential. Once infected, pregnant women should be given timely antiviral treatments, which could effectively alleviate the disease progression and reduce adverse outcomes. Besides, the mechanism of viral hepatitis mediating adverse pregnancy outcomes has been a hot topic. Hepatitis B virus has been found to mediate both mother- to-child and parent-child transmission. Liver injury in hepatitis C virus infection is associated with immune-mediated mechanisms, which can be regulated by hormonal factors as well. The mediating mechanism of adverse maternal and infant outcomes caused by hepatitis E virus infection is mainly related to viral replication in the placenta and changes in cytokine and estrogen. Nevertheless, the specific mechanisms related to hepatitis A virus and hepatitis D virus remain unclear, and more research is needed. This review shows that the existence of viral hepatitis during pregnancy can pose certain risks for pregnant women and infants, and different interventions have been used to treat pregnant women infected with viral hepatitis. It may provide deep insight into adverse pregnancy outcomes caused by viral hepatitis and give guidance on treatment., Competing Interests: Conflict of Interest The authors have declared no conflicts of interest., (© 2024 Jian Wu, Huiqing Wang, Ze Xiang, Chun Jiang, Yunyang Xu, Guanghua Zhai, Zongxin Ling, published by De Gruyter on behalf of Scholar Media Publishing.)

Background: Metabolic syndrome (MetS) is highly prevalent in individuals with schizophrenia (SZ), leading to negative consequences like premature mortality. Gut dysbiosis, which refers to an imbalance of the microbiota, and chronic inflammation are associated with both SZ and MetS. However, the relationship between gut dysbiosis, host immunological dysfunction, and SZ comorbid with MetS (SZ-MetS) remains unclear. This study aims to explore alterations in gut microbiota and their correlation with immune dysfunction in SZ-MetS, offering new insights into its pathogenesis., Methods and Results: We enrolled 114 Chinese patients with SZ-MetS and 111 age-matched healthy controls from Zhejiang, China, to investigate fecal microbiota using Illumina MiSeq sequencing targeting 16 S rRNA gene V3-V4 hypervariable regions. Host immune responses were assessed using the Bio-Plex Pro Human Cytokine 27-Plex Assay to examine cytokine profiles. In SZ-MetS, we observed decreased bacterial α-diversity and significant differences in β-diversity. LEfSe analysis identified enriched acetate-producing genera (Megamonas and Lactobacillus), and decreased butyrate-producing bacteria (Subdoligranulum, and Faecalibacterium) in SZ-MetS. These altered genera correlated with body mass index, the severity of symptoms (as measured by the Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms), and triglyceride levels. Altered bacterial metabolic pathways related to lipopolysaccharide biosynthesis, lipid metabolism, and various amino acid metabolism were also found. Additionally, SZ-MetS exhibited immunological dysfunction with increased pro-inflammatory cytokines, which correlated with the differential genera., Conclusion: These findings suggested that gut microbiota dysbiosis and immune dysfunction play a vital role in SZ-MetS development, highlighting potential therapeutic approaches targeting the gut microbiota. While these therapies show promise, further mechanistic studies are needed to fully understand their efficacy and safety before clinical implementation., (© 2024. The Author(s).)

Copper dysmetabolism is associated with various neurodegenerative disorders, making high-spatiotemporal-resolution imaging of Cu 2+ in the brain essential for understanding the underlying pathophysiological processes. Nevertheless, the current probes encounter obstacles in crossing the blood-brain barrier (BBB) and providing high-spatial-resolution in deep tissues. Herein, we present a photoacoustic probe capable of imaging Cu 2+ dynamics in the mouse brain with high-spatiotemporal-resolution. The probe demonstrates selective ratiometric and reversible responses to Cu 2+ , while also efficiently crossing the BBB. Using the probe as the imaging agent, we successfully visualized Cu 2+ in the brain of Parkinson's disease (PD) model mouse with a remarkable micron-level resolution. The imaging results revealed a significant increase in Cu 2+ levels in the cerebral cortex as PD progresses, highlighting the close association between Cu 2+ alternations in the region and the disease. We also demonstrated that the probe can be used to monitor changes in Cu 2+ distribution in the PD model mouse brain during L-dopa intervention. Mechanism studies suggest that the copper dyshomeostasis in the PD mouse brain was dominated by the expression levels of divalent metal transporter 1. The application of our probe in imaging Cu 2+ dynamics in the mouse brain offers valuable insights into the copper-related molecular mechanisms underlying neurodegenerative diseases., (© 2024 Wiley-VCH GmbH.)

Background: Hypertension (HTN) and chronic kidney disease (CKD) pose significant global health challenges and often coexist, amplifying cardiovascular risks. Recent attention has turned to the gut mycobiome as a potential factor in their pathophysiology. Our study sought to examine the gut fungal profile in individuals with HTN, CKD, and the concurrent HTN+CKD condition, investigating its connections with serum cytokines, renal function, and blood pressure., Methods and Materials: We investigated three distinct participant groups: a cohort of 50 healthy controls (HC), 50 individuals diagnosed with HTN-only, and 50 participants suffering from both HTN and CKD (HTN+CKD). To facilitate our research, we gathered fecal and blood samples and conducted a comprehensive analysis of serum cytokines. Moreover, fungal DNA extraction was conducted with meticulous care, followed by sequencing of the Internal Transcribed Spacer (ITS) region., Results: HTN+CKD patients displayed distinctive fungal composition with increased richness and diversity compared to controls. In contrast, HTN-only patients exhibited minimal fungal differences. Specific fungal genera were notably altered in HTN+CKD patients, characterized by increased Apiotrichum and Saccharomyces levels and reduced Candida abundance. Our correlation analyses revealed significant associations between fungal genera and serum cytokines. Moreover, certain fungal taxa, such as Apiotrichum and Saccharomyces , exhibited positive correlations with renal function, while others, including Septoria , Nakaseomyces , and Saccharomyces , were linked to blood pressure, particularly diastolic pressure., Conclusion: Gut mycobiome dysbiosis in individuals with comorbid HTN and CKD differs significantly from that observed in HTN-only and healthy controls. The interactions between serum cytokines, renal function, and blood pressure emphasize the potential impact of the fungal microbiome on these conditions. Additional research is required to clarify the underlying mechanisms and identify therapeutic opportunities associated with mycobiome dysbiosis in HTN and CKD., 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 © 2023 Qiu, Zhao, Cheng, Chen, Xu, Lu, Gao, Lei, Yan, Ling and Wu.)

Schizophrenia (SZ) is a complex psychiatric neurodevelopmental disorder with uncertain etiology and pathogenesis. Increasing evidence has recognized the key role of the gut microbiota in SZ. However, few studies have investigated the potential link between oral microbiota and SZ. We studied the tongue coating microbiota and inflammatory profiles of 118 elderly SZ patients and 97 age-matched healthy controls using Illumina MiSeq sequencing and multiplex immunoassays, respectively. Reduced α-diversity, along with a significant difference in β-diversity, were observed in patients with SZ. We have identified SZ-associated oral dysbiosis, characterized by increased Streptococcus and Fusobacterium, as well as decreased Prevotella and Veillonella. These differential genera could potentially serve as biomarkers for SZ, either alone or in combination. Additionally, an elevated Streptococcus/Prevotella ratio could indicate oral dysbiosis. These differential genera formed two distinct clusters: Streptococcus-dominated and Prevotella-dominated, which exhibited different correlations with the altered immunological profiles. Furthermore, we also observed disruptions in the inferred microbiota functions in SZ-associated microbiota, particularly in lipid and amino acid metabolism. Our study provides novel insights into the characteristics of tongue coating microbiota and its associations with immunological disturbances in elderly SZ patients, which offer new targets for the diagnosis and treatment of SZ in the elderly., (© 2023. The Author(s).)

Both schizophrenia (SZ) and multiple sclerosis (MS) affect millions of people worldwide and impose a great burden on society. Recent studies indicated that MS elevated the risk of SZ and vice versa, whereas the underlying pathological mechanisms are still obscure. Considering that fecal microbiota played a vital role in regulating brain functions, the fecal microbiota and serum cytokines from 90 SZ patients and 71 age-, gender-, and BMI-matched cognitively normal subjects (referred as SZC), 22 MS patients and 33 age-, gender-, and BMI-matched healthy subjects (referred as MSC) were analyzed. We found that both diseases demonstrated similar microbial diversity and shared three differential genera, including the down-regulated Faecalibacterium , Roseburia , and the up-regulated Streptococcus . Functional analysis indicated that the three genera were involved in pathways such as "carbohydrate metabolism" and "amino acid metabolism." Moreover, the variation patterns of serum cytokines associated with MS and SZ patients were a bit different. Among the six cytokines perturbed in both diseases, TNF- α increased, while IL-8 and MIP-1 α decreased in both diseases. IL-1ra, PDGF-bb, and RANTES were downregulated in MS patients but upregulated in SZ patients. Association analyses showed that Faecalibacterium demonstrated extensive correlations with cytokines in both diseases. Most notably, Faecalibacterium correlated negatively with TNF- α . In other words, fecal microbiota such as Faecalibacterium may contribute to the coexistence of MS and SZ by regulating serum cytokines. Our study revealed the potential roles of fecal microbiota in linking MS and SZ, which paves the way for developing gut microbiota-targeted therapies that can manage two diseases with a single treat., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Li Shao et al.)

An accumulating body of evidence suggests that the bacterium Akkermansia muciniphila exhibits positive systemic effects on host health, mainly by improving immunological and metabolic functions, and it is therefore regarded as a promising potential probiotic. Recent clinical and preclinical studies have shown that A. muciniphila plays a vital role in a variety of neuropsychiatric disorders by influencing the host brain through the microbiota-gut-brain axis (MGBA). Numerous studies observed that A. muciniphila and its metabolic substances can effectively improve the symptoms of neuropsychiatric disorders by restoring the gut microbiota, reestablishing the integrity of the gut mucosal barrier, regulating host immunity, and modulating gut and neuroinflammation. However, A. muciniphila was also reported to participate in the development of neuropsychiatric disorders by aggravating inflammation and influencing mucus production. Therefore, the exact mechanism of action of A. muciniphila remains much controversial. This review summarizes the proposed roles and mechanisms of A. muciniphila in various neurological and psychiatric disorders such as depression, anxiety, Parkinson's disease, Alzheimer's disease, multiple sclerosis, strokes, and autism spectrum disorders, and provides insights into the potential therapeutic application of A. muciniphila for the treatment of these conditions., 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 © 2023 Lei, Cheng, Gao, Liu, Shao, Kong, Zheng, Ling and Hu.)

Non-alcoholic fatty liver disease (NAFLD) represents a growing global health concern that can lead to liver disease and cancer. It is characterized by an excessive accumulation of fat in the liver, unrelated to excessive alcohol consumption. Studies indicate that the gut microbiota-host crosstalk may play a causal role in NAFLD pathogenesis, with epigenetic modification serving as a key mechanism for regulating this interaction. In this review, we explore how the interplay between gut microbiota and the host epigenome impacts the development of NAFLD. Specifically, we discuss how gut microbiota-derived factors, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), can modulate the DNA methylation and histone acetylation of genes associated with NAFLD, subsequently affecting lipid metabolism and immune homeostasis. Although the current literature suggests a link between gut microbiota and NAFLD development, our understanding of the molecular mechanisms and signaling pathways underlying this crosstalk remains limited. Therefore, more comprehensive epigenomic and multi-omic studies, including broader clinical and animal experiments, are needed to further explore the mechanisms linking the gut microbiota to NAFLD-associated genes. These studies are anticipated to improve microbial markers based on epigenetic strategies and provide novel insights into the pathogenesis of NAFLD, ultimately addressing a significant unmet clinical need., Competing Interests: The authors have declared no conflicts of interest., (© 2023 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH.)

Background: The scrotum is considered as an uncommon site for tinea, hence there is a lack of knowledge about the clinical characteristics, pathogenic agents and the skin microbiome changes of tinea scrotum., Objective: We sought to analyze the clinical features, pathogenic agents and skin microbiome of tinea scrotum., Methods: A two-center prospective observational study was carried out in outpatient dermatology clinics in Zhejiang, China, from September 2017 to September 2019. The diagnosis of tinea scrotum was confirmed by direct microscopy. Clinical and mycological data were collected. The composition of microbial communities of patients with tinea scrotum was analyzed and compared with healthy controls., Results: A total of 113 patients with tinea scrotum were included. Tinea scrotum was either presented with isolated lesions (9/113, 8.0%) or accompanied by tinea of other sites (104/113, 92.0%). Tinea cruris was detected in 101 cases (89.38%). Fungal culture was positive in 63 cases, among which Trichophyton rubrum was grown in 60 cases (95.2%) and Nannizzia gypsea was cultured in 3 cases (4.8%). The skin microbiome in scrotum lesions from 18 patients showed increased abundance of Trichophyton compared with 18 healthy individuals, while Malassezia was decreased. No significant difference in bacterial diversity was found., Conclusions: Tinea scrotum was often companied by superficial fungal infections of other skin sites, with tinea cruris being the most common condition. Instead of N. gypsea, T. rubrum was the most frequently identified pathogen for tinea scrotum. In general, tinea scrotum exhibited changes in the fungal communities of the skin with increased Trichophyton and decreased Malassezia abundance., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Depression is one of the most common psychiatric conditions, characterized by significant and persistent depressed mood and diminished interest, and often coexists with various comorbidities. The underlying mechanism of depression remain elusive, evidenced by the lack of an appreciate therapy. Recent abundant clinical trials and animal studies support the new notion that the gut microbiota has emerged as a novel actor in the pathophysiology of depression, which partakes in bidirectional communication between the gut and the brain through the neuroendocrine, nervous, and immune signaling pathways, collectively known as the microbiota-gut-brain (MGB) axis. Alterations in the gut microbiota can trigger the changes in neurotransmitters, neuroinflammation, and behaviors. With the transition of human microbiome research from studying associations to investigating mechanistic causality, the MGB axis has emerged as a novel therapeutic target in depression and its comorbidities. These novel insights have fueled idea that targeting on the gut microbiota may open new windows for efficient treatment of depression and its comorbidities. Probiotics, live beneficial microorganisms, can be used to modulate gut dysbiosis into a new eubiosis and modify the occurrence and development of depression and its comorbidities. In present review, we summarize recent findings regarding the MGB axis in depression and discuss the potential therapeutic effects of probiotics on depression and its comorbidities., 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 © 2023 Gao, Zhao, Cheng, Lei, Wang, Liu, Zheng, Shao, Chen, Sun, Ling and Xu.)

Background: Exploring the human microbiome in multiple body niches is beneficial for clinicians to determine which microbial dysbiosis should be targeted first. We aimed to study whether both the fecal and vaginal microbiomes are disrupted in SLE patients and whether they are correlated, as well as their associations with immunological features., Methods: A group of 30 SLE patients and 30 BMI-age-matched healthy controls were recruited. Fecal and vaginal samples were collected, the 16S rRNA gene was sequenced to profile microbiomes, and immunological features were examined., Results: Distinct fecal and vaginal bacterial communities and decreased microbial diversity in feces compared with the vagina were found in SLE patients and controls. Altered bacterial communities were found in the feces and vaginas of patients. Compared with the controls, the SLE group had slightly lower gut bacterial diversity, which was accompanied by significantly higher bacterial diversity in their vaginas. The most predominant bacteria differed between feces and the vagina in all groups. Eleven genera differed in patients' feces; for example, Gardnerella and Lactobacillus increased, whereas Faecalibacterium decreased. Almost all the 13 genera differed in SLE patients' vaginas, showing higher abundances except for Lactobacillus . Three genera in feces and 11 genera in the vagina were biomarkers for SLE patients. The distinct immunological features were only associated with patients' vaginal microbiomes; for example, Escherichia-Shigella was negatively associated with serum C4., Conclusions: Although SLE patients had fecal and vaginal dysbiosis, dysbiosis in the vagina was more obvious than that in feces. Additionally, only the vaginal microbiome interacted with patients' immunological features., 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 © 2023 Ling, Cheng, Gao, Lei, Yan, Hu, Shao, Liu and Kang.)

Gastric cancer (GC) is one of the most common malignant tumors with a high incidence and mortality. Microbiota play a significant role in human health and disease. We aimed to investigate the prognostic value of the gastric microbiota in different stomach microhabitats. We used our previously published 16S rRNA gene sequence data. We retrospectively enrolled a cohort of 132 patients with GC with complete prognostic information and selected 78 normal tissues, 49 peritumoral tissues, and 112 tumoral tissues for microbiota analysis. Patients with different prognoses showed different gastric microbiota compositions and diversity. The association network of the abundant gastric microbiota was more complicated in patients with poor prognoses. In the peritumoral microhabitat of patients with good prognoses, Helicobacter was significantly increased, whereas Halomonas and Shewanella were significantly decreased relative to that in the peritumoral microhabitat of patients with poor prognoses. PiCRUSt analysis revealed that the peritumoral microbiota had more different Kyoto Encyclopedia of Genes and Genomes pathways than did the tumoral and normal microbiota. This study evaluated the long-term prognostic value of the gastric mucosal microbiota in patients with GC. These findings suggested that the characteristic alterations of the gastric mucosal microbiota may be markers for clinical outcomes in these patients., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The gut microbiome is involved in metabolic disorders. Osteopontin (OPN), as a key cytokine, contributes to various inflammation-related diseases. The underlying role of OPN in the microbiome remains poorly understood. Here, we investigated whether OPN could modulate metabolic disorders by affecting gut microbiota. In our present study, we found that the expression of OPN was elevated in individuals with obesity compared to that observed in healthy controls. There was a positive correlation between plasma OPN levels and body mass index (BMI) in humans. Moreover, OPN significantly exacerbated lipid accumulation and metabolic disorders in high-fat diet (HFD)-fed mice. Importantly, OPN significantly aggravated HFD-induced gut dysbiosis with a key signature profile. Fecal microbiota transplantation also supported the role of OPN in HFD-induced metabolic disorders in a microbiota-dependent manner. Moreover, the microbiome shift of OPN-deficient mice would be compensated to resemble those of wild-type mice by feeding with either OPN-containing milk or recombinant OPN protein in vivo . Furthermore, metagenomic analysis showed that OPN induced a higher abundance of Dorea and a lower abundance of Lactobacillus , which were positively and negatively correlated with body weight, respectively. Indeed, the abundance of Dorea was significantly decreased after Lactobacillus administration, suggesting that OPN may regulate the intestinal abundance of Dorea by reducing the colonization of Lactobacillus . We further confirmed that OPN decreased the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. This study suggested that OPN could exacerbate HFD-induced metabolic dysfunctions through the OPN-induced alteration of the gut microbiome. Therefore, OPN could be a potential therapeutic target for metabolic syndrome. IMPORTANCE Gut microbiota are involved in metabolic disorders. However, microbiome-based therapeutic interventions are not always effective, which might be due to interference of the host factors. Here, we identified a strong positive correlation between OPN levels and BMI in humans. Next, we confirmed that OPN could aggravate high-fat diet-induced metabolic disorders in mice. Importantly, we found that fecal microbiota transplantation from OPN-deficient mice significantly alleviated metabolic disorders in WT mice. OPN directly induces the remodeling of the gut microbiota both in vitro and in vivo . These findings indicate that OPN could contribute to metabolic disorders by inducing an alteration of gut microbiota. OPN regulated the relative abundance of Lactobacillus by decreasing the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. These data identify OPN as a potential pharmaceutical target for weight control and for the treatment of metabolic disorders.

Recent evidence suggests that lung microbiota can be recognized as one of the ecological determinants of various respiratory diseases. However, alterations in the lung microbiota and associated lung immunity in these respiratory diseases remain unclear. To compare the lung microbiota and lung immune profiles in common respiratory diseases, a total of 78 patients were enrolled in the present study, including 21 patients with primary pulmonary tuberculosis (PTB), eight patients with newly diagnosed lung cancer (LC), and 49 patients with community-acquired pneumonia (CAP). Bronchoalveolar lavage fluid (BALF) was collected for microbiota and cytokine analyses. With MiSeq sequencing system, increased bacterial alpha-diversity and richness were observed in patients with LC than in those with PTB and CAP. Linear discriminant analysis effect size revealed that CAP-associated pulmonary microbiota were significantly different between the PTB and LC groups. More key functionally different genera were found in the PTB and LC groups than in the CAP group. The interaction network revealed stronger positive and negative correlations among these genera in the LC group than in the other two groups. However, increased BALF cytokine profiles were observed in the PTB group than in the other two groups, while BALF cytokines were correlated with key functional bacteria. This comparative study provides evidence for the associations among altered lung microbiota, BALF inflammation, and different respiratory disorders, which provides insight into the possible roles and mechanisms of pulmonary microbiota in the progression of respiratory disorders., 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 © 2022 Xia, Chen, Cheng, Chen, Lu, Liu, Wang, Pu, Wang, Liu, Cao, Zhang, Xia, Fan, Ling and Zhao.)

Depression in childhood negatively affects the growth and development, school performance, and peer or family relationships of affected children, and may even lead to suicide. Despite this, its etiology and pathophysiology remain largely unknown. Increasing evidence supports that gut microbiota plays a vital role in the development of childhood depression. However, little is known about the underlying mechanisms, as most clinical studies investigating the link between gut microbiota and depression have been undertaken in adult cohorts. In present study, a total of 140 school-aged children (6-12 years) were enrolled, including 92 with depression (male/female: 42/50) and 48 healthy controls (male/female: 22/26) from Lishui, Zhejiang, China. Illumina sequencing of the V3-V4 region of the 16S rRNA gene was used to investigate gut microbiota profiles while Bio-Plex Pro Human Cytokine 27-plex Panel was employed to explore host immune response. We found that, compared with healthy controls, children with depression had greater bacterial richness and altered β-diversity. Pro-inflammatory genera such as Streptococcus were enriched in the depression group, whereas anti-inflammatory genera such as Faecalibacterium were reduced, as determined by linear discriminant analysis effect size. These changes corresponded to altered bacterial functions, especially the production of immunomodulatory metabolites. We also identified the presence of a complex inflammatory condition in children with depression, characterized by increased levels of pro-inflammatory cytokines such as IL-17 and decreased levels of anti-inflammatory cytokines such as IFN-γ. Correlation analysis demonstrated that the differential cytokine abundance was closely linked to changes in gut microbiota of children with depression. In summary, key functional genera, such as Streptococcus and Faecalibacterium , alone or in combination, could serve as novel and powerful non-invasive biomarkers to distinguish between children with depression from healthy ones. This study was the first to demonstrate that, in Chinese children with depression, gut microbiota homeostasis is disrupted, concomitant with the activation of a complex pro-inflammatory response. These findings suggest that gut microbiota might play an important role in the pathogenesis of depression in school-aged children, while key functional bacteria in gut may serve as novel targets for non-invasive diagnosis and patient-tailored early precise intervention in children with depression., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Ling, Cheng, Chen, Yan, Liu, Shao, Jin, Zhou, Jiang, Li, Zhao and Song.)

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis is involved in the occurrence, development and progression of PD. Numerous clinical trials have identified the characteristics of the changed gut microbiota profiles, and preclinical studies in PD animal models have indicated that gut dysbiosis can influence the progression and onset of PD via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels of α-synuclein fibrils, increasing oxidative stress, and decreasing neurotransmitter production. The gut microbiota can be considered promising diagnostic and therapeutic targets for PD, which can be regulated by probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, diet modifications, and Chinese medicine. This review summarizes the recent studies in PD-associated gut microbiota profiles and functions, the potential roles, and mechanisms of gut microbiota in PD, and gut microbiota-targeted interventions for PD. Deciphering the underlying roles and mechanisms of the PD-associated gut microbiota will help interpret the pathogenesis of PD from new perspectives and elucidate novel therapeutic strategies for PD., 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 © 2022 Zhu, Liu, Ye, Yan, Cheng, Zhao, Chen and Ling.)

Schizophrenia (SZ) is a severe neuropsychiatric disorder with largely unknown etiology and pathogenesis. Mounting preclinical and clinical evidence suggests that the gut microbiome is a vital player in SZ. However, the gut microbiota characteristics and its host response in elderly SZ patients are still not well understood. A total of 161 samples was collected, including 90 samples from elderly SZ patients and 71 samples from healthy controls. We explored the gut microbiota profiles targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with host immune response. Our data found that bacterial β-diversity analyses could divide the SZ patients and healthy controls into two different clusters. The Linear discriminant analysis Effect Size (LEfSe) identified the compositional changes in SZ-associated bacteria, including Faecalibacterium , Roseburia , Actinomyces , Butyricicoccus , Prevotella and so on. In addition, the levels of pro-inflammatory cytokines such as IL-1β were greatly increased in SZ patients while the levels of anti-inflammatory cytokines such as IFN-γ were markedly decreased. Correlation analysis suggested that these bacteria contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the SZ patients from healthy controls. Moreover, several predicted functional modules, including increased lipopolysaccharide biosynthesis, folate biosynthesis, lipoic acid metabolism, and decreased bile acid biosynthesis, fatty acid biosynthesis in SZ-associated microbiota, could be utilized by the bacteria to produce immunomodulatory metabolites. This study, for the first time, demonstrated the structural and functional dysbiosis of the fecal microbiota in Chinese elderly SZ patients, suggesting the potential for using gut key functional bacteria for the early, non-invasive diagnosis of SZ, personalized treatment, and the development of tailor-made probiotics designed for Chinese elderly SZ patients., 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 © 2022 Ling, Jin, Yan, Cheng, Shao, Song, Liu and Zhao.)

Gastric cancer (GC) is the fifth most common neoplasm and the third most deadly cancer in humans worldwide. Helicobacter pylori infection is the most important causative factor of gastric carcinogenesis, and activates host innate and adaptive immune responses. As key constituents of the tumor immune microenvironment, plasmacytoid dendritic cells (pDCs) are increasingly attracting attention owing to their potential roles in immunosuppression. We recently reported that pDCs have vital roles in the development of immunosuppression in GC. Clarifying the contribution of pDCs to the development and progression of GC may lead to improvements in cancer therapy. In this review, we summarize current knowledge regarding immune modulation in GC, especially the roles of pDCs in GC carcinogenesis and treatment strategies., 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 © 2022 Yang, Liu, Cheng, Zhang, Ji and Ling.)

Secreted phosphoprotein 1 ( SPP1 ) is involved in immune regulation, cell survival, and tumor progression. Studies have demonstrated that SPP1 plays an important role in certain individual tumors. However, the expression profile and oncogenic features of SPP1 in diverse cancers are remaining unknown. Therefore, we performed a comprehensive analysis using The Cancer Genome Atlas (TCGA) database. Raw data of 33 cancer types were download from the University of California Santa Cruz (UCSC) Xena website. The expression of SPP1 and its relationship with tumor prognosis, immune invasion, tumor microenvironment, and immunotherapy were analyzed using the R language. The function analysis was conducted using Gene Set Enrichment Analysis (GSEA). The oncogenic features of SPP1 was validated by wound-healing assay and EdU staining assay. SPP1 highly expressed in most cancers. The expression of SPP1 was significant related to prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint genes, suggested that SPP1 plays an essential role in the tumor immune microenvironment and immune cell infiltration. The immune/stromal scores correlated positively with the SPP1 expression, and the relationship was affected by tumor heterogeneity and immunotherapy. In addition, SPP1 could predict the response of tumor immunotherapy. Functional analysis revealed the SPP1 -associated terms and pathways. Finally, SPP1 significantly elevated cell proliferation and migration in A549, Huh7, HT-29, A2780 tumor cell lines. In conclusion, this study indicated that SPP1 involved in tumorigenesis, tumor progression, and regulated tumor immune microenvironment, revealing SPP1 might be a potential target for evaluating prognosis and immunotherapy in multiple cancers.

Few studies have focused on the effect of hepatitis E virus (HEV) infection on gut microbiota. To explore the relationship between changes in gut microbiota and inflammatory factors and viral load, we conducted a comparative study of 33 patients with acute hepatitis E (AHE) patients and 25 healthy controls (HCs) using high-throughput 16S ribosomal ribonucleic acid gene sequencing. Shannon and Simpson's indices showed no significant differences in bacterial diversity between the AHE and HCs groups. Proteobacteria, Gammaproteobacteria, and Enterobacteriaceae were most abundant in the AHE group, which contributed to the difference between the gut microbiota of the AHE and HCs groups, and the same difference between the HEV-RNA-positive and HEV-RNA-negative groups. Functional prediction analysis showed that ribosome, purine metabolism, and two-component system were the top three pathways. Compared with the AHE group with normal interferon (IFN)-γ, Proteobacteria, Gammaproteobacteria, Xanthomonadaceae, and Enterobacteriaceae were more abundant in the high-IFN-γ group. The abundance of Gammaproteobacteria was positively correlated with the level of serum alanine transaminase and total bilirubin. The abundance of Gammaproteobacteria could discriminate AHE patients from HCs, and could better predict the severity of AHE patients. We believe that our findings will contribute toward a novel treatment strategy for AHE., (© 2021 Wiley Periodicals LLC.)

Aging is characterized by the functional decline of tissues and organs and increased risk of aging-associated disorders, which pose major societal challenges and are a public health priority. Despite extensive human genetics studies, limited progress has been made linking genetics with aging. There is a growing realization that the altered assembly, structure and dynamics of the gut microbiota actively participate in the aging process. Age-related microbial dysbiosis is involved in reshaping immune responses during aging, which manifest as immunosenescence (insufficiency) and inflammaging (over-reaction) that accompany many age-associated enteric and extraenteric diseases. The gut microbiota can be regulated, suggesting a potential target for aging interventions. This review summarizes recent findings on the physiological succession of gut microbiota across the life-cycle, the roles and mechanisms of gut microbiota in healthy aging, alterations of gut microbiota and aging-associated diseases, and the gut microbiota-targeted anti-aging strategies.

Psychobiotics-live microorganisms with potential mental health benefits, which can modulate the microbiota-gut-brain-axis via immune, humoral, neural, and metabolic pathways-are emerging as novel therapeutic options for the effective treatment of psychiatric disorders Recently, microbiome studies have identified numerous putative psychobiotic strains, of which short-chain fatty acids (SCFAs) producing bacteria have attracted special attention from neurobiologists. Recent studies have highlighted that SCFAs-producing bacteria such as Lactobacillus , Bifidobacterium and Clostridium have a very specific function in various psychiatric disorders, suggesting that these bacteria can be potential novel psychobiotics. SCFAs, potential mediators of microbiota-gut-brain axis, might modulate function of neurological processes. While the specific roles and mechanisms of SCFAs-producing bacteria of microbiota-targeted interventions on neuropsychiatric disease are largely unknown. This Review summarizes existing knowledge on the neuroprotective effects of the SCFAs-producing bacteria in neurological disorders via modulating microbiota-gut-brain axis and illustrate their possible mechanisms by which SCFAs-producing bacteria may act on these disorders, which will shed light on the SCFAs-producing bacteria as a promising novel source of psychobiotics.

Lactobacillus iners , first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus , in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases., 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 © 2021 Zheng, Guo, Wang, Zhou and Ling.)

Small organic photothermal agents (SOPTAs) that absorb in the second near-infrared (NIR-II, 1000-1700 nm) window are highly desirable in photothermal therapy for their good biocompatibility and deeper tissue penetration. However, the design of NIR-II absorbing SOPTAs remains a great challenge. Herein, we report that molecular engineering of BF 2 complex via strengthening the donor-acceptor conjugation and increasing the intramolecular motions is an efficient strategy to achieve NIR-II absorbing SOPTAs with high photothermal performance. Based on this strategy, a BF 2 complex, BAF4, was designed and synthesized. BAF4 exhibits an intense absorption maximum at 1000 nm and negligible fluorescence. Notably, the nanoparticles of BAF4 achieve a high photothermal conversion efficiency value of 80 % under 1064 nm laser irradiation (0.75 W cm -2 ). In vitro and in vivo studies reveal the great potential of BAF4 nanoparticles in photoacoustic imaging-guided photothermal therapy in the NIR-II window., (© 2021 Wiley-VCH GmbH.)

The low viability during gastrointestinal transit and poor mucoadhesion considerably limits the effectiveness of Ligilactobacillus salivarius Li01 (Li01) in regulating gut microbiota and alleviating inflammatory bowel disease (IBD). In this study, a delivery system was designed through layer-by-layer (LbL) encapsulating a single Li01cell with chitosan and alginate. The layers were strengthened by cross-linking to form a firm and mucoadhesive shell (~10 nm thickness) covering the bacterial cell. The LbL Li01 displayed improved viability under simulated gastrointestinal conditions and mucoadhesive function. Almost no cells could be detected among the free Li01 after 2 h incubation in digestive fluids, while for LbL Li01, the total reduction was around 3 log CFU/mL and the viable number of cells remained above 6 log CFU/mL. Besides, a 5-fold increase in the value of rupture length and a two-fold increase in the number of peaks were found in the (bacteria-mucin) adhesion curves of LbL Li01, compared to those of free Li01. Oral administration with LbL Li01 on colitis mice facilitated intestinal barrier recovery and restoration of the gut microbiota. The improved functionality of Li01 by LbL encapsulation could increase the potential for the probiotic to be used in clinical applications to treat IBD; this should be explored in future studies., (© 2021. The Author(s).)

Alzheimer's disease (AD) is the most common age-related progressive neurodegenerative disease, characterized by a decline in cognitive function and neuronal loss, and is caused by several factors. Numerous clinical and experimental studies have suggested the involvement of gut microbiota dysbiosis in patients with AD. The altered gut microbiota can influence brain function and behavior through the microbiota-gut-brain axis via various pathways such as increased amyloid-β deposits and tau phosphorylation, neuroinflammation, metabolic dysfunctions, and chronic oxidative stress. With no current effective therapy to cure AD, gut microbiota modulation may be a promising therapeutic option to prevent or delay the onset of AD or counteract its progression. Our present review summarizes the alterations in the gut microbiota in patients with AD, the pathogenetic roles and mechanisms of gut microbiota in AD, and gut microbiota-targeted therapies for AD. Understanding the roles and mechanisms between gut microbiota and AD will help decipher the pathogenesis of AD from novel perspectives and shed light on novel therapeutic strategies for AD., 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 © 2021 Wu, Liu, Jiang, Yan and Ling.)

The development of sequencing technology has expanded our knowledge of the human gastric microbiome, which is now known to play a critical role in the maintenance of homeostasis, while alterations in microbial community composition can promote the development of gastric diseases. Recently, carcinogenic effects of gastric microbiome have received increased attention. Gastric cancer (GC) is one of the most common malignancies worldwide with a high mortality rate. Helicobacter pylori is a well-recognized risk factor for GC. More than half of the global population is infected with H. pylori , which can modulate the acidity of the stomach to alter the gastric microbiome profile, leading to H. pylori -associated diseases. Moreover, there is increasing evidence that bacteria other than H. pylori and their metabolites also contribute to gastric carcinogenesis. Therefore, clarifying the contribution of the gastric microbiome to the development and progression of GC can lead to improvements in prevention, diagnosis, and treatment. In this review, we discuss the current state of knowledge regarding changes in the microbial composition of the stomach caused by H. pylori infection, the carcinogenic effects of H. pylori and non- H. pylori bacteria in GC, as well as the potential therapeutic role of gastric microbiome in H. pylori infection and GC., 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 © 2021 Yang, Zhou, Liu, Ling and Ji.)

Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization., 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 © 2021 Han, Lu, Xie, Fei, Zheng, Wang, Liu, Lv, Ling, Berglund, Yao and Li.)

Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of gut-brain disorders, such as Alzheimer's disease (AD). However, alterations of the gut microbiota as well as their correlations with cognitive scores and host immunity have remained unclear in well-controlled trials on Chinese AD patients. In this study, samples from 100 AD patients, and 71 age- and gender-matched, cognitively normal controls were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with clinical characteristics. Our data demonstrated a remarkably reduction in the bacterial diversity and alterations in the taxonomic composition of the fecal microbiota of the AD patients. Interestingly, the abundant butyrate-producing genera such as Faecalibacterium decreased significantly, where this was positively correlated with such clinical indicators as the MMSE, WAIS, and Barthel scores in the AD patients. On the contrary, abundant lactate-producing genera, such as Bifidobacterium , increased prominently, and were inversely correlated with these indicators. This shift in the gut dysbiosis of the microbiota, from being butyrate producers to lactate producers, contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the controls from the AD patients. Moreover, several predicted functional modules, including the biosynthesis and the metabolism of fatty acids, that were altered in the microbiota of the AD patients could be utilized by the bacteria to produce immunomodulatory metabolites. Our study established the structural and functional dysbiosis of fecal microbiota in AD patients, and the results suggest the potential for use of gut bacteria for the early, non-invasive diagnosis of AD, personalized treatment, and the development of tailor-made probiotics designed for Chinese AD patients., 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 © 2021 Ling, Zhu, Yan, Cheng, Shao, Liu, Jiang and Wu.)

Gut bacterial dysbiosis plays a vital role in the development of Alzheimer's disease (AD). However, our understanding of alterations to the gut fungal microbiota and their correlations with host immunity in AD is still limited. Samples were obtained from 88 Chinese patients with AD, and 65 age- and gender-matched, cognitively normal controls. Using these samples, we investigated the fungal microbiota targeting internal transcribed spacer 2 (ITS2) rRNA genes using MiSeq sequencing, and analyzed their associations with the host immune response. Our data demonstrated unaltered fungal diversity but altered taxonomic composition of the fecal fungal microbiota in the AD patients. The analysis of the fungal microbiota was performed using 6,585,557 high-quality reads (2,932,482 reads from the controls and 3,653,075 from the AD patients), with an average of 43,042 reads per sample. We found that several key differential fungi such as Candida tropicalis and Schizophyllum commune were enriched in the AD patients, while Rhodotorula mucilaginosa decreased significantly. Interestingly, C. tropicalis and S. commune were positively correlated with IP-10 and TNF-α levels. In contrast, C. tropicalis was negatively correlated with IL-8 and IFN-γ levels, and R. mucilaginosa was negatively correlated with TNF-α level. PiCRUSt analysis revealed that lipoic acid metabolism, starch and sucrose metabolism were significantly decreased in the AD fungal microbiota. This study is the first to demonstrate fecal fungal dysbiosis in stable AD patients at a deeper level, and to identify the key differential fungi involved in regulating host systemic immunity. The analysis of the fungal microbiota in AD performed here may provide novel insights into the etiopathogenesis of AD and pave the way for improved diagnosis and treatment of AD., 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 © 2021 Ling, Zhu, Liu, Shao, Cheng, Yan, Jiang and Wu.)

Type 2 diabetes mellitus (T2DM) influences the human health and can cause significant illnesses. The genitourinary microbiome profiles in the T2DM patients remain poorly understood. In the current study, a series of bioinformatic and statistical analyses were carried out to determine the multiple bacteria associated with the more dysbiotic genitourinary microbiomes (i.e., those with lower dysbiosis ratio) in T2DM patients, which were sequenced by Illumina-based 16S rRNA gene amplicon sequencing. All the genitourinary microbiomes from 70 patients with T2DM were clustered into three clusters of microbiome profiles, i.e., Cluster_1_T2DM, Cluster_2_T2DM and Cluster_3_T2DM, with Cluster_3_T2DM at the most dysbiotic genitourinary microbial status. The three clustered T2DM microbiomes were determined with different levels of alpha diversity indices, and driven by distinct urinalysis variables. OTU12_Clostridiales and OTU28_Oscillospira were likely to drive the T2DM microbiomes to more dysbiotic status, while OTU34_Finegoldia could play a vital role in maintaining the least dysbiotic T2DM microbiome (i.e., Cluster_1_T2DM). The functional metabolites K08300_ribonuclease E, K01223_6-phospho-beta-glucosidase and K00029_malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) were most associated with Cluster_1_T2DM, Cluster_2_T2DM and Cluster_3_T2DM, respectively. The characteristics and multiple bacteria associated with the more dysbiotic genitourinary microbiomes in T2DM patients may help with the better diagnosis and management of genitourinary dysbiosis in T2DM patients.

A connection between gut microbiota and Parkinson's disease (PD) indicates that dysbiosis of the gut microbiota might represent a risk factor for PD. Microbiota-targeted interventions, including probiotic Clostridium butyricum (Cb), have been recently shown to have favorable effects in PD by regulating microbiota-gut-brain axis. However, the potential beneficial roles and its mechanisms of Cb on PD were still unknown. Male C57BL/6 mice were subjected to a PD model-induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and were treated intragastrically with Cb for 4 weeks. The motor functions were assessed by a series of behavioral tests including pole test, beam walking teat, forced swimming test and open field test. The dopaminergic neuron loss, synaptic plasticity and microglia activation, as well as the levels of colonic glucagon-like peptide-1 (GLP-1), colonic G protein-coupled receptors GPR41/43 and cerebral GLP-1 receptors were assessed. Gut microbial composition was assessed by 16S rRNA sequencing analysis. Our results showed that oral administration of Cb could improve motor deficits, dopaminergic neuron loss, synaptic dysfunction and microglia activation in the MPTP-induced mice. Meanwhile, Cb treatment could reverse the dysbiosis of gut microbiota and the decreased levels of colonic GLP-1, colonic GPR41/43 and cerebral GLP-1 receptor in the MPTP-induced mice. These findings indicated that the neuroprotective mechanism of Cb on PD might be related to the improvement of abnormal gut microbiota-gut-brain axis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS. In our study, 22 Chinese patients with stable MS and 33 healthy controls were enrolled for fecal microbiota analysis and host immunity evaluation. The microbial diversity and composition, bacterial co-occurrence correlations, predictive functional profiles, and microbiota-cytokine correlations between the two groups were compared. We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium , decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS and healthy controls with an area under the curve of 0.832. PiCRUSt analysis revealed that genes associated with fructose, mannose, and fatty acid metabolism were significantly enriched in the MS microbiota. In addition, we also observed that the levels of several pro- and anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-8, IL-17, and TNF-α changed observably, and the abundances of key functional bacteria like butyrate producers correlated with the changes in the cytokine levels. Our present study indicated that altered composition of the fecal microbiota might play vital roles in the etiopathogenesis of MS by regulating host immunity, which suggests that microbiota-targeting patient-tailored early intervention techniques might serve as novel therapeutic approaches for MS., 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 © 2020 Ling, Cheng, Yan, Shao, Liu, Zhou, Zhang, Yu and Zhao.)

The intestinal microbiota, composed of a large population of microorganisms, is often considered a "forgotten organ" in human health and diseases. Increasing evidence indicates that dysbiosis of the intestinal microbiota is closely related to colorectal cancer (CRC). The roles for intestinal microorganisms that initiated and facilitated the CRC process are becoming increasingly clear. Hypothesis models have been proposed to illustrate the complex relationship between the intestinal microbiota and CRC. Recent studies have identified Streptococcus bovis , enterotoxigenic Bacteroides fragilis , Fusobacterium nucleatum , Enterococcus faecalis , Escherichia coli , and Peptostreptococcus anaerobius as CRC candidate pathogens. In this review, we summarized the mechanisms involved in microbiota-related colorectal carcinogenesis, including inflammation, pathogenic bacteria, and their virulence factors, genotoxins, oxidative stress, bacterial metabolites, and biofilm. We also described the clinical values of intestinal microbiota and novel strategies for preventing and treating CRC., 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 © 2020 Cheng, Ling and Li.)

Fulminant hepatitis E may lead to acute liver failure (ALF). Perturbations of intestinal microbiota are related to severe liver disease. To study the correlations between faecal microbiota and the occurrence and exacerbation of hepatitis E virus (HEV) infection, we characterized 24 faecal samples from 12 patients with acute hepatitis E (AHE) and 12 patients with HEV-ALF using high-throughput sequencing. We found both the alpha and beta diversity indices showed no significant differences between the AHE and HEV-ALF groups. Several predominant taxa were significantly different between the AHE and HEV-ALF groups. Most notably, the HEV-ALF group had increased levels of Gammaproteobacteria, Proteobacteria, Xanthomonadceae and Stenotrophomonas, but reduced levels of Firmicutes, Streptococcus, Subdoligranulum and Lactobacillus, compared with the AHE group. The levels of Lactobacillaceae and Gammaproteobacteria could be used to distinguish patients with HEV-ALF from those with AHE. In addition, the level of Th lymphocytes was significantly lower in the HEV-ALF group than in the AHE group. The relative abundances of Lactobacillaceae and Gammaproteobacteria were positively correlated with Th lymphocytes, serum international normalized ratio (INR) and hepatic encephalopathy severity. Moreover, surviving patients had higher levels of Lactobacillus mucosae than deceased patients. Our study demonstrated that the presence of altered faecal microbiota is associated with exacerbation of HEV infection; this finding may be useful for exploring the interactions among faecal microbiota, immune responses, mechanisms of infection and progression in patients with HEV, as well as for the development of novel diagnostic and therapeutic strategies., (© 2020 John Wiley & Sons Ltd.)

Growing evidence indicated that the gut microbiota was the intrinsic and essential component of the cancer microenvironment, which played vital roles in the development and progression of colorectal cancer (CRC). In our present study, we investigated the alterations of fecal abundant microbiota with real-time quantitative PCR and the changes of indicators of gut mucosal barrier from 53 early-stage CRC patients and 45 matched healthy controls. We found that the traditional beneficial bacteria such as Lactobacillus and Bifidobacterium decreased significantly and the carcinogenic bacteria such as Enterobacteriaceae and Fusobacterium nucleatum were significantly increased in CRC patients. We also found gut mucosal barrier dysfunction in CRC patients with increased levels of endotoxin (LPS), D-lactate, and diamine oxidase (DAO). With Pearson's correlation analysis, D-lactate, LPS, and DAO were correlated negatively with Lactobacillus and Bifidobacterium and positively with Enterobacteriaceae and F. nucleatum . Our present study found dysbiosis of the fecal microbiota and dysfunction of the gut mucosal barrier in patients with early-stage CRC, which implicated that fecal abundant bacteria and gut mucosal barrier indicators could be used as targets to monitor the development and progression of CRC in a noninvasive and dynamic manner., 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 © 2020 Xia Liu et al.)

Background: Our previous study demonstrated that the composition of the urinary microbiota in female patients with type 2 diabetes mellitus (T2DM) was correlated with the concentration of urinary interleukin (IL)-8. As the composition of urine is mainly determined by diet, diet might mediate the correlation., Methods: Seventy female T2DM patients and 70 healthy controls (HCs) were recruited. Midstream urine was used for the urine specimens. Urinary IL-8 was determined by enzyme-linked immunosorbent assay. A Chinese Food Frequency Questionnaire was used to collect food intake data. The independent variables in the hierarchical regression analysis were the relative abundances of the bacterial genera and species that were significantly different between the T2DM and HCs and between the T2DM patients with and without detectable urinary IL-8, and the bacterial genera associated with IL-8 concentration in the multiple regression model reported in our previous research. IL-8 concentration was the dependent variable, and nutrient intakes were moderator variables., Results: Fiber and vitamin B3 and E intake exerted enhancing effects, and water intake exerted a buffering effect, on the positive relationship between the relative abundance of Ruminococcus and IL-8 concentration ( p < 0.05). Cholesterol and magnesium intake exerted enhancing effects on the positive relationship between the relative abundance of Comamonas and IL-8 concentration ( p < 0.05)., Conclusion: Modulating T2DM patients' dietary patterns may prevent bladder inflammation., Competing Interests: The authors declare that they have no competing interests., (© 2020 Liu et al.)

Scope: Recent evidences demonstrate that abnormal gut microbiota (GM) might be involved in the pathogenesis of Alzheimer's disease (AD). However, the role of probiotics in preventing AD by regulating GM-gut-brain axis remains unclear. Here, the anti-neuroinflammatory effect and its mechanism of probiotic Clostridium butyricum (CB) against AD is investigated by regulating GM-gut-brain axis., Methods and Results: APPswe/PS1dE9 (APP/PS1) transgenic are treated intragastrically with CB for 4 weeks then cognitively tested. Amyloid-β (Aβ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, Aβ-induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase-2 (COX-2), and NF-κB p65 phosphorylation are determined. The results show that CB treatment prevents cognitive impairment, Aβ deposits, microglia activation, and production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the brain of APP/PS1 mice. Meanwhile, abnormal GM and butyrate are reversed after CB treatment. Notably, butyrate treatment reduces the levels of CD11b and COX-2, and suppresses phosphorylation of NF-κB p65 in the Aβ-induced BV2 microglia., Conclusions: These findings indicate that CB treatment could attenuate microglia-mediated neuroinflammation via regulating the GM-gut-brain axis, which is mediated by the metabolite butyrate., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vaginal dysbiosis has been identified to be associated with adverse pregnancy outcomes, such as preterm delivery and premature rupture of membranes. However, the overall structure and composition of vaginal microbiota in different trimesters of the pregnant women has not been fully elucidated. In this study, the physiological changes of the vaginal microbiota in healthy pregnant women were investigated. A total of 83 healthy pregnant participants were enrolled, who are in the first, second, or third pregnancy trimester. Quantitative real-time PCR was used to explore the abundant bacteria in the vaginal microbiota. No significant difference in the abundance of Gardnerella , Atopobium , Megasphaera , Eggerthella , Leptotrichia / Sneathia , or Prevotella was found among different trimesters, except Lactobacillus . Compared with the first pregnancy trimester, the abundance of L. iners decreased in the second and third trimester while the abundance of L. crispatus was increased in the second trimester. Moreover, we also found that vaginal cleanliness is correlated with the present of Lactobacillus , Atopobium , and Prevotella and leukocyte esterase is associated with Lactobacillus , Atopobium , Gardnerella , Eggerthella , Leptotrichia / Sneathia , and Prevotella . For those whose vaginal cleanliness raised or leukocyte esterase became positive, the richness of L. iners increased, while that of L. crispatus decreased significantly. Our present data indicated that the altered vaginal microbiota, mainly Lactobacillus , could be observed among different trimesters of pregnancy and L. iners could be considered as a potential bacterial marker for evaluating vaginal cleanliness and leukocyte esterase., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2019 Nengneng Zheng et al.)

As one of the most important cariogenic pathogens, Streptococcus mutans has strong abilities to form biofilms, produce acid and tolerate acid. In present study, we found that theaflavin-3,3'-digallate (TF3) had an inhibitory effect on S. mutans UA159 in vitro . Visualized by field emission-scanning electron microscopy, the suppressed formation of S. mutans biofilms grown with TF3 at sub-inhibitory concentrations could be attributed to the reduced biofilm matrix, which was proven to contain glucans and extracellular DNA (eDNA). Glucan-reduced effect of TF3 was achieved by down-regulating expression levels of gtfB, gtfC , and gtfD encoding glucosyltransferases. Besides, TF3 reduced eDNA formation of S. mutans by negatively regulating lrgA, lrgB , and srtA , which govern cell autolysis and membrane vesicle components. Furthermore, TF3 also played vital roles in antagonizing preformed biofilms of S. mutans . Bactericidal effects of TF3 became significant when its concentrations increased more than twofold of minimum inhibitory concentration (MIC). Moreover, the capacities of S. mutans biofilms to produce acid and tolerate acid were significantly weakened by TF3 at MIC. Based on real-time PCR (RT-PCR) analysis, the mechanistic effects of TF3 were speculated to comprise the inhibition of enolase, lactate dehydrogenase, F-type ATPase and the agmatine deiminase system. Moreover, TF3 has been found to downregulate LytST, VicRK, and ComDE two component systems in S. mutans , which play critical roles in the regulatory network of virulence factors. Our present study found that TF3 could suppress the formation and cariogenic capacities of S. mutans biofilms, which will provide new strategies for anti-caries in the future.

Substantial evidence indicates that gastric microbiota dysbiosis, immune system dysfunction especially immune escape are critical for gastric cancer (GC) occurrence and progression. As two important elements of tumor microenvironment (TME), the relationship between gastric microbiota and tumor-immune microenvironment is still unclear. Our present study aimed to explore the correlation between gastric mucosal microbiota in different microhabitats and its corresponding gastric immunosuppressive cells such as regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) in the TME. A cohort of 64 GC patients without preoperative chemotherapy was enrolled retrospectively, and 60 normal, 61 peritumoral and 59 tumoral tissues were obtained for gastric mucosal microbiota analysis and immunohistochemistry analysis. From different microhabitats, BDCA2 + pDCs and Foxp3 + Tregs were observed positively correlated, and increased in tumoral and peritumoral tissues compared to normal ones. The diversity, composition and function of gastric mucosal microbiota also changed more significantly in tumoral tissues than those in normal and peritumoral ones. With pearson's correlation analysis, we found that several non-abundant genera such as Stenotrophomonas and Selenomonas were positively correlated with BDCA2 + pDCs and Foxp3 + Tregs, respectively, while Comamonas and Gaiella were negatively correlated with BDCA2 + pDCs and Foxp3 + Tregs, respectively. The increased BDCA2 + pDCs and Foxp3 + Tregs might be modulated by gastric mucosal microbiota, both participated in the immunosuppression microenvironment of GC, which might provide evidence to establish new strategies in antitumor therapy targeting on gastric microbiota.

Alzheimer's disease (AD) is closely related to gut microbial alteration. Prebiotic fructooligosaccharides (FOS) play major roles by regulating gut microbiota. The present study aimed to explore the effect and mechanism of FOS protection against AD via regulating gut microbiota. Male Apse/PSEN 1dE9 (APP/PS1) transgenic (Tg) mice were administrated with FOS for 6 weeks. Cognitive deficits and amyloid deposition were evaluated. The levels of synaptic plasticity markers including postsynaptic density protein 95 (PSD-95) and synapsin I, as well as phosphorylation of c-Jun N-terminal kinase (JNK), were determined. The intestinal microbial constituent was detected by 16S rRNA sequencing. Moreover, the levels of glucagon-like peptide-1 (GLP-1) in the gut and GLP-1 receptor (GLP-1R) in the brain were measured. The results indicated that FOS treatment ameliorated cognitive deficits and pathological changes in the Tg mice. FOS significantly upregulated the expression levels of synapsin I and PSD-95, as well as decreased phosphorylated level of JNK. The sequencing results showed that FOS reversed the altered microbial composition. Furthermore, FOS increased the level of GLP-1 and decreased the level of GLP-1R in the Tg mice. These findings indicated that FOS exerted beneficial effects against AD via regulating the gut microbiota-GLP-1/GLP-1R pathway.

Background: The mechanisms of mesenchymal stem cell (MSC) transplantation to protect against acute liver injury have been well studied within the liver. However, the associated changes in the intestinal microbiota during this process are poorly understood., Methods: In this study, compact bone-derived MSCs were injected into mice after carbon tetrachloride (CCl 4 ) administration. Potential curative effect of MSC was evaluated by survival rate and biochemical and pathological results. Overall structural changes of microbial communities and alterations in the intestinal microbiota were assessed by sequenced 16S rRNA amplicon libraries from the contents of the cecum and colon., Results: MSCs significantly reduced the serum levels of aspartate transaminase and alanine transaminase and improved the histopathology and survival rate. Lower expression and discontinuous staining of zonula occludens, as well as disrupted tight junctions, were observed in CCl 4 -treated mice at 48 h compared with MSC-transplanted mice. Moreover, MSC transplantation to the liver leads to intestinal microbiota changes that were reflected in the decreased abundance of Bacteroidetes S24-7 and Bacteroidaceae and increased abundance of Firmicutes Clostridiales , Ruminococcaceae , and Lactobacillus at the initial time point compared with that in CCl 4 -treated mice. In addition, phylogenetic investigation of communities by the reconstruction of unobserved states (PICRUSt) based on the Greengenes database revealed functional biomarkers of MSC-transplanted mice involved in cell motility, signal transduction, membrane transport, transcription, and metabolism of lipids, cofactors, vitamins, terpenoids, and polyketides, as well as xenobiotics., Conclusion: The initial alterations in the Firmicutes/Bacteroidetes ratio, which resulted from MSC infusion to the liver, maintain intestinal mucosal biology and homeostasis that may be beneficial to liver repair.

Background: As part of the tumor microenvironment, the gastric microbiota play vital roles in tumor initiation, progression and metastasis, but stomach microhabitats are not always uniform. We aimed to characterize differences of gastric microbiota in stomach microhabitats associated with gastric cancer (GC) development., Methods: A cohort of 276 GC patients without preoperative chemotherapy was enrolled retrospectively, and 230 normal, 247 peritumoral and 229 tumoral tissues were obtained for gastric microbiota analysis targeting the 16S rRNA gene by MiSeq sequencing. The microbial diversity and composition, bacterial co-occurrence correlations and predictive functional profiles were compared across different microhabitats., Findings: GC-specific stomach microhabitats, not GC stages or types, determine the composition and diversity of the gastric microbiota. Most notably, bacterial richness was decreased in peritumoral and tumoral microhabitats, and the correlation network of abundant gastric bacteria was simplified in tumoral microhabitat. Helicobacter pylori (HP), Prevotella copri and Bacteroides uniformis were significantly decreased, whereas Prevotella melaninogenica, Streptococcus anginosus and Propionibacterium acnes were increased in tumoral microhabitat. Higher HP colonisation influenced the overall structure of the gastric microbiota in normal and peritumoral microhabitats. PiCRUSt analysis revealed that genes associated with nucleotide transport and metabolism and amino acid transport and metabolism were significantly enriched in tumoral microbiota, while gastric acid secretion was significantly higher in HP positive group of the tumoral microbiota., Interpretation: Our present study provided new insights into the roles of gastric microbiota in different stomach microhabitats in gastric carcinogenesis, especially the pathogenesis of HP. FUND: National Natural Science Foundation of China., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Mycoplasma pneumoniae is one of the most common pathogens causing community-acquired pneumonia in children. Mycoplasma pneumoniae pneumonia (MPP) can be successfully treated with azithromycin; however, antibiotic-associated diarrhea (AAD) is a common adverse effect. Increasing evidence suggests that some probiotics may prevent the development of AAD. The present study determined the effects of probiotics (live Clostridium butyricum plus Bifidobacterium infantis ) on the prevention and treatment of AAD in children with MPP when co-administered with intravenous azithromycin. Fifty-five children with MPP were enrolled and received azithromycin (10 mg/kg/day; once daily for 7 days) combined with probiotics (starting on the third day of azithromycin treatment; 1,500 mg three times daily); 50 healthy children served as controls. At the end of the trial, the incidence of AAD, fecal microbiota, intestinal mucosal barriers, and systemic inflammation were analyzed using recommended systems biology techniques. No cases of AAD or other adverse events occurred in children with MPP after co-administration of probiotics with azithromycin. A live C. butyricum plus B. infantis preparation partly reconstructed the gut microbiota, especially restoration of bacterial diversity. The indicators of intestinal mucosal barrier function, such as D-lactate, endotoxin, and diamine oxidase, were significantly improved and the systemic inflammation (interleukin 10) was attenuated after probiotic therapy. The present study indicated that co-administration of probiotics with azithromycin is a promising therapy for MPP treatment which could prevent and treat AAD effectively.

Early detection and effective interventions for liver cirrhosis (LC) remain an urgent unmet clinical need. Inspired from intestinal disorders in LC patients, we investigated the associations between gut microbiome and disease progression based on a raw metagenomic dataset of 47 healthy controls, 49 compensated, and 46 decompensated LC patients from our previous study, and a metabolomic dataset of urine samples from the same controls/patients using ultra-performance liquid chromatography/mass spectrophotometry system. It was found that the combination and relative abundance of gut microbiome, the inter-microbiome regulatory networks, and the microbiome-host correlation patterns varied during disease progression. The significant reduction of bacteria involved in fermentation of plant cell wall polysaccharides and resistant starch (such as Alistipes sp. HG5 , Clostridium thermocellum ) contributed to the reduced supply of energy sources, the disorganized self-feeding and cross-feeding networks and the thriving of some opportunistic pathogens in genus Veillonella . The marked decrease of butyrate-producing bacteria and increase of Ruminococcus gnavus implicated in degradation of elements from the mucus layer provided an explanation for the impaired intestinal barrier function and systematic inflammation in LC patients. Our results pave the way for further developments in early detection and intervention of LC targeting on gut microbiome.

Objective This study was performed to investigate the role of probiotics ( Clostridium butyricum combined with Bifidobacterium infantis) in the treatment of minimal hepatic encephalopathy (MHE) in patients with hepatitis B virus (HBV)-induced liver cirrhosis. Methods Sixty-seven consecutive patients with HBV-induced cirrhosis without overt hepatic encephalopathy were screened using the number connection test and digit symbol test. The patients were randomized to receive probiotics (n = 30) or no probiotics (n = 37) for 3 months. At the end of the trial, changes in cognition, intestinal microbiota, venous ammonia, and intestinal mucosal barriers were analyzed using recommended systems biology techniques. Results The patients' cognition was significantly improved after probiotic treatment. The predominant bacteria ( Clostridium cluster I and Bifidobacterium) were significantly enriched in the probiotics-treated group, while Enterococcus and Enterobacteriaceae were significantly decreased. Probiotic treatment was also associated with an obvious reduction in venous ammonia. Additionally, the parameters of the intestinal mucosal barrier were obviously improved after probiotic treatment, which might have contributed to the improved cognition and the decreased ammonia levels. Conclusion Treatment with probiotics containing C. butyricum and B. infantis represents a new adjuvant therapy for the management of MHE in patients with HBV-induced cirrhosis.

Dynamic alterations in oral microbiota are closely related to the development of dental caries;however, changes in salivary microbiota during this process have not been extensively studied. In addition, increasing evidence suggests that oral microbiome profiles differ according to dentition stages, but it is unclear whether they change with age during the same dentition, such as deciduous dentition. These two aspects were investigated in a 2-year follow-up study, and caries-free preschool children with complete deciduous dentition were enrolled. Saliva was collected and oral examination was conducted at the beginning of this trial, and then every subsequent 6 months for a total of five time points (T0, T1, T2, T3, and T4). Based on the clinical examination of teeth at the end of the trial, subjects were divided into health-to-health (H-H, N = 11) and health-to-caries (H-C, N = 12) groups at every time point. A total of 115 saliva samples from 23 subjects was detected by sequencing 16S rDNA V3-V4 hypervariable regions with the Illumina MiSeq platform to obtain microbiome profiles, and 100 samples finally passed quality control for further analyses. A total of 4,328,852 high-quality sequencing reads passed quality-control testing, representing 14 phyla, 27 classes, 43 orders, 67 families, and 127 genera. An α diversity analysis showed that salivary microbial diversity was similar in all groups, and a β diversity analysis showed that salivary microbial community structure changed with dental caries. Linear discriminant analysis effect size (LEfSe) analysis revealed that the abundance of the genera Atopobium, Megasphaera , and Veillonella increased significantly, while that of the genera Shuttleworthia and Rothia decreased significantly with the development of dental caries. Megasphaera and Veillonella were enriched at the early stage of deciduous dentition whereas Peptococcus, Rothia , and Treponema were enriched at the later stage. The core microbiome in the H-H and H-C groups comprised 26 and 29 genera, respectively, with statistical differences observed in 11 shared core genera. These results provide new insights into variations in the salivary microbiome related to dental caries and age in the deciduous dentition period.

Farnesylation, which is catalyzed by farnesyltransferase, is an important posttranslational process. The function of farnesyltransferase has been previously explored in Cryptococcus neoformans and Candida albicans. Aspergillus fumigatus is an important human opportunistic fungal pathogen in immunocompromised patients. Here we discover the role of the ram1 gene, encoding the β-subunit of farnesyltransferase in A. fumigatus, in the fungal growth and antifungal susceptibility. In this study the ram1 gene was disrupted using A. tumefaciens-mediated transformation. The morphology and radial growth of Δram1 were observed. Assays of disk diffusion and broth microdilution were used to determine the susceptibility of Δram1 mutant to commonly clinical used antifungals and the farnesyltransferase inhibitor manumycin A. Deletion of ram1 resulted in a reduced radial growth of A. fumigatus but did not affect the microscopic morphology. Δram1 showed increased susceptibility to the antifungal amphotericin B; however, its susceptibility to azoles and caspofungin was the same to that to the parental strain. Our data indicate that farnesyltransferase is a potential target for design new antifungal agents., (© The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Evidence shows that urine has complex bacterial profiles with considerable variation between individuals. Aging and age-related conditions can lead to the changes to the composition of urine, which means that the available nutrition for bacteria in the bladder changes with age. We explored the characteristics of the urinary microbiota of elderly women and whether these are associated with age-related conditions such as diabetes and urinary tract infections. An elderly and a non-elderly cohort of women were included. Magnetic beads were used to isolate bacterial genomic DNA, which was analyzed based on the V3-V4 hypervariable region of the 16S rRNA gene. There were significant differences between the elderly and non-elderly regarding thirteen genera of bacteria. For example, the relative abundance of Lactobacillus was dramatically reduced in the elderly compared with the non-elderly; it also decreased with age in the elderly cohort and it was not correlated with urine pH. The relative abundance of Peptococcus increased with age in the elderly while the abundance of Bifidobacteria decreased with age. The abundance of Escherichia coli was the same in the two cohorts, and it increased with water intake and was not associated with urinary tract infection events. Higher levels of Lactobacillus (including Lactobacillus iners ) in the elderly were associated with diabetes, and lower levels of Peptoniphilus and Dialister were correlated with asymptomatic bacteriuria. The urinary microbiota of women is affected by ageing, type 2 diabetes mellitus and asymtomatic bacteriuria., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.