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Background: The interplay between gut microbiota (GM) and the metabolization of dietary components leading to the production of short-chain fatty acids (SCFAs) is affected by a range of factors including colonic pH and carbohydrate source. However, there is still only limited knowledge on how the GM activity and metabolite production in the gastrointestinal tract could be influenced by pH and the pH gradient increases along the colon. Results: Here we investigate the effect of pH gradients corresponding to levels typically found in the colon on GM composition and metabolite production using substrates inulin, lactose, galactooligosaccharides (GOS), and fructooligosaccharide (FOS) in an in vitro colon setup. We investigated 3 different pH regimes (low, 5.2 increasing to 6.4; medium, 5.6 increasing to 6.8 and high, 6.0 increasing to 7.2) for each fecal inoculum and found that colonic pH gradients significantly influenced in vitro simulated GM structure, but the influence of fecal donor and substrate was more pronounced. Low pH regimes strongly influenced GM with the decreased relative abundance of Bacteroides spp. and increased Bifidobacterium spp. Higher in vitro simulated colonic pH promoted the production of SCFAs in a donor- and substrate-dependent manner. The butyrate producer Butyricimonas was enriched at higher pH conditions, where also butyrate production was increased for inulin. The relative abundance of Phascolarctobacterium, Bacteroides, and Rikenellaceae also increased at higher colonic pH, which was accompanied by increased production of propionate with GOS and FOS as substrates. Conclusions: Together, our results show that colonic substrates such as dietary fibres influence GM composition and metabolite production, not only by being selectively utilized by specific microbes, but also because of their SCFA production, which in turn also influences colonic pH and overall GM composition and activity. Our work provides details about the effect of the gradients of rising pH from the proximal to distal colon on fermenting dietary substrates in vitro and highlights the importance of considering pH in GM research. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota plays an important role in human health, as it can affect host immunity and susceptibility to infectious diseases. Invasive intestinal candidiasis is strongly associated with gut microbiota homeostasis. However, the nature of the interaction between Candida albicans and gut bacteria remains unclear. Objective: This review aimed to determine the nature of interaction and the effects of gut bacteria on C. albicans so as to comprehend an approach to reducing intestinal invasive infection by C. albicans. Methods: This review examined 11 common gut bacteria's interactions with C. albicans, including Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus faecalis, Staphylococcus aureus, Salmonella spp., Helicobacter pylori, Lactobacillus spp., Bacteroides spp., Clostridium difficile, and Streptococcus spp. Results: Most of the studied bacteria demonstrated both synergistic and antagonistic effects with C. albicans, and just a few bacteria such as P. aeruginosa, Salmonella spp., and Lactobacillus spp. demonstrated only antagonism against C. albicans. Conclusions: Based on the nature of interactions reported so far by the literature between gut bacteria and C. albicans, it is expected to provide new ideas for the prevention and treatment of invasive intestinal candidiasis. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile infection (CDI) has a high recurrent infection rate. Faecal microbiota transplantation (FMT) has been used successfully to treat recurrent CDI, but much remains unknown about the human gut microbiota response to replacement therapies. In this study, antibiotic-mediated dysbiosis of gut microbiota and bacterial growth dynamics were investigated by two quantitative methods: real-time quantitative PCR (qPCR) and direct culture enumeration, in triple-stage chemostat models of the human colon. Three in vitro models were exposed to clindamycin to induce simulated CDI. All models were treated with vancomycin, and two received an FMT. Populations of total bacteria, Bacteroides spp., Lactobacillus spp., Enterococcus spp., Bifidobacterium spp., C. difficile, and Enterobacteriaceae were monitored using both methods. Total clostridia were monitored by selective culture. Using qPCR analysis, we additionally monitored populations of Prevotella spp., Clostridium coccoides group, and Clostridium leptum group. Results: Both methods showed an exacerbation of disruption of the colonic microbiota following vancomycin (and earlier clindamycin) exposure, and a quicker recovery (within 4 days) of the bacterial populations in the models that received the FMT. C. difficile proliferation, consistent with CDI, was also observed by both qPCR and culture. Pearson correlation coefficient showed an association between results varying from 98% for Bacteroides spp., to 62% for Enterobacteriaceae. Conclusions: Generally, a good correlation was observed between qPCR and bacterial culture. Overall, the molecular assays offer results in real-time, important for treatment efficacy, and allow the monitoring of additional microbiota groups. However, individual quantification of some genera (e.g. clostridia) might not be possible without selective culture. [ABSTRACT FROM AUTHOR]

Background: The association between microbes and cancer has been reported repeatedly; however, it is not clear if molecular tumour properties are connected to specific microbial colonisation patterns. This is due mainly to the current technical and analytical strategy limitations to characterise tumour-associated bacteria. Methods: Here, we propose an approach to detect bacterial signals in human RNA sequencing data and associate them with the clinical and molecular properties of the tumours. The method was tested on public datasets from The Cancer Genome Atlas, and its accuracy was assessed on a new cohort of colorectal cancer patients. Results: Our analysis shows that intratumoural microbiome composition is correlated with survival, anatomic location, microsatellite instability, consensus molecular subtype and immune cell infiltration in colon tumours. In particular, we find Faecalibacterium prausnitzii, Coprococcus comes, Bacteroides spp., Fusobacterium spp. and Clostridium spp. to be strongly associated with tumour properties. Conclusions: We implemented an approach to concurrently analyse clinical and molecular properties of the tumour as well as the composition of the associated microbiome. Our results may improve patient stratification and pave the path for mechanistic studies on microbiota-tumour crosstalk. [ABSTRACT FROM AUTHOR]

Background: Ginsenoside compound K (GC-K) potentially alleviates ulcerative colitis involved in gut microbiota, which is significantly associated with the occurrence and development of colitis. However, the effect and mechanism of GC-K on anti-colitis in relation to gut microbiota are not clear. This study focused on the prevention and mechanism of GC-K on Dextran sulfate sodium (DSS)-induced colitis of mice pertinent to gut microbiota. Methods: DSS was used to establish a chronic colitis mouse model. Body weight analysis, colon length measurement, HE staining, and inflammatory factors levels were processed in animal experiments. Flow cytometry was employed to analyze Th17/Treg cells in the mouse spleen and blood. 16S rRNA sequencing was utilized to analyze gut microbiota. Fecal microbiota transplantation (FMT) experiment was employed to verify the anti-colitis efficacy of GC-K by reshaping gut microbiota. Results: GC-K significantly relieved colitis-related symptoms due to decreased disease activity index (DAI) scores, spleen weight, and increased colon length. Additionally, the tight junction proteins were increased, and the pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β and IL-17, were decreased after GC-K treatment. Furthermore, Bacteroides spp. significantly increased after modeling. Moreover, FMT experiments confirmed that GC-K-driven gut microbiota greatly relieved DSS-induced colitis. Conclusion: GC-K alleviated colitis via the modulation of gut microbiota. Highlights: Ginsenoside Compound K (GC-K) alleviated colitis in DSS-induced Mice. GC-K modulated gut microbiota in DSS-induced mice. GC-K relieved colitis via regulating gut microbiota. GC-K-driven gut microbial effectively ameliorated colitis. [ABSTRACT FROM AUTHOR]

Background: Improving probiotic engraftment in the human gut requires a thorough understanding of the in vivo adaptive strategies of probiotics in diverse contexts. However, for most probiotic strains, these in vivo genetic processes are still poorly characterized. Here, we investigated the effects of gut selection pressures from human, mice, and zebrafish on the genetic stability of a candidate probiotic Lactiplantibacillus plantarum HNU082 (Lp082) as well as its ecological and evolutionary impacts on the indigenous gut microbiota using shotgun metagenomic sequencing in combination with isolate resequencing methods. Results: We combined both metagenomics and isolate whole genome sequencing approaches to systematically study the gut-adaptive evolution of probiotic L. plantarum and the ecological and evolutionary changes of resident gut microbiomes in response to probiotic ingestion in multiple host species. Independent of host model, Lp082 colonized and adapted to the gut by acquiring highly consistent single-nucleotide mutations, which primarily modulated carbohydrate utilization and acid tolerance. We cultivated the probiotic mutants and validated that these gut-adapted mutations were genetically stable for at least 3 months and improved their fitness in vitro. In turn, resident gut microbial strains, especially competing strains with Lp082 (e.g., Bacteroides spp. and Bifidobacterium spp.), actively responded to Lp082 engraftment by accumulating 10–70 times more evolutionary changes than usual. Human gut microbiota exhibited a higher ecological and genetic stability than that of mice. Conclusions: Collectively, our results suggest a highly convergent adaptation strategy of Lp082 across three different host environments. In contrast, the evolutionary changes within the resident gut microbes in response to Lp082 were more divergent and host-specific; however, these changes were not associated with any adverse outcomes. This work lays a theoretical foundation for leveraging animal models for ex vivo engineering of probiotics to improve engraftment outcomes in humans. 1TYRt-mQpEqyYou2DA7bqR Video abstract [ABSTRACT FROM AUTHOR]

Background: Correctly identifying anaerobic bloodstream infections (BSIs) is difficult. However, a new technique, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), enables more accurate identification and appropriate treatment. Anaerobic BSIs identified by MALDI-TOF MS were retrospectively analyzed to determine the clinical and microbiological features and patient outcomes based on the anaerobic genera or group. Methods: Medical records of patients with anaerobic BSIs were used to conduct a single-center retrospective cohort study from January 2016 to December 2020 in Nagoya, Japan. Multivariate logistic regression analysis was performed to determine the independent risk factors for in-hospital mortality. Results: Of the 215 patients with anaerobic BSIs, 31 had multiple anaerobic organisms in the blood culture, including 264 total episodes of anaerobic BSIs. Bacteroides spp. were isolated the most (n = 74), followed by gram-positive non-spore-forming bacilli (n = 57), Clostridium spp. (n = 52), gram-positive anaerobic cocci (GPAC) (n = 27), and gram-negative cocci (n = 7). The median patient age was 76 years; 56.7% were male. The most common focal infection site was intra-abdominal (36.7%). The in-hospital mortality caused by anaerobic BSIs was 21.3%, and was highest with Clostridium spp. (36.5%) and lowest with GPAC (3.7%). Age, solid tumors, and Clostridium spp. were independent risk factors for in-hospital mortality. Conclusions: We identified current anaerobic BSI trends using MALDI-TOF MS and reported that mortality in patients with anaerobic BSIs patients was highest with Clostridium spp. infections. [ABSTRACT FROM AUTHOR]

Short-chain fatty acids, especially butyrate, play beneficial roles in sustaining gastrointestinal health. However, due to limitations associated with direct consumption of butyrate, there has been interest in using prodrugs of butyrate. Tributyrin (TB), a triglyceride composed of three butyrate molecules and a glycerol, is a well-studied precursor of butyrate. We screened a metagenome library consisting of 5760 bacterial artificial chromosome clones, with DNA inserts originating from mouse microbiomes, and identified two clones that efficiently hydrolyse TB into butyrate. Nucleotide sequence analysis indicated that inserts in these two clones are derived from unknown microbes. BLASTp analysis, however, revealed that each insert contains a gene homologous to acetylesterase or esterase genes, from Clostridium spp. and Bacteroides spp., respectively. Predicted structures of these two proteins both contain serine-histidine-aspartate catalytic triad, highly conserved in the family of esterases. Escherichia coli host expressing each of the two candidate genes invariably produced greater amounts of butyrate in the presence of TB. Importantly, administration of TB together with cloned E. coli cells alleviated inflammatory symptoms in a mouse model of acute colitis. Based on these results, we established an efficient on-site and real-time butyrate production system that releases butyrate in a controlled manner inside the intestine. [ABSTRACT FROM AUTHOR]

Background: Vaginitis is among the most common conditions women are seeking medical care for. Although these infections can easily be treated, the relapse rate is high. This may be due to inadequate use of the diagnostic potential. Methods: We evaluated the misjudgment rate of the aetiology of vaginal complaints. A total of 220 vaginal samples from women with a vaginal complaint were obtained and analysed for numbers of total lactobacilli, H2O2-producing lactobacilli, total aerobic cell counts and total anaerobic cell counts including bifidobacteria, Bacteroides spp., Prevotella spp. Additionally, the presence of Atopobium vaginae, Gardnerella vaginalis, Candida spp. and Trichomonas vaginalis was evaluated by DNA-hybridisation using the PCR and Affirm VPIII Microbial Identification Test, respectively. Results: The participating physicians diagnosed Bacterial vaginosis (BV) as origin of discomfort in 80 cases, candidiasis in 109 cases and mixed infections in 8 cases. However, a present BV, defined as lack of H2O2-lactobacilli, presence of marker organisms, such as G. vaginalis, Bacteroides spp. or Atopobium vaginae, and an elevated pH were identified in only 45 cases of the women examined. Candida spp. were detected in 46 cases. Interestingly, an elevated pH corresponded solely to the presence of Atopobium vaginae, which was detected in 11 cases. Conclusion: Errors in the diagnosis of BV and candida vulvovaginitis (CV) were high. Interestingly, the cases of misjudgement of CV (77%) were more numerous than that of BV (61%). The use of Amsel criteria or microscopy did not reduce the number of misinterpretations. The study reveals that the misdiagnosis of vaginal complaints is rather high. [ABSTRACT FROM AUTHOR]

Background: Synthetic human milk oligosaccharides (HMOs) are used to supplement infant formula despite limited understanding of their impact on the post-weaned developing gut microbiota. Here, we assess the influence of 0.5 g/L 2-fucosyllactose (2'FL) and 4.0 g/L pooled HMOs (pHMOs) on the composition and activity of cultured fecal-derived microbial communities from seven healthy young children. Results: Exposure to pHMOs induced significant shifts in both the microbial community composition and metabolic output, including an increased abundance of several genera, notably Bacteroides, and the production of health-associated metabolites. In contrast, 2'FL alone did not lead to substantial changes in the communities. A total of 330 bacterial isolates, spanning 157 species, were cultured from these communities and individually evaluated for their responses to HMOs. Over 100 non-Bifidobacterium species showed enhanced growth upon pHMOs treatment and a high degree of intraspecies variation in HMO metabolism was observed. Conclusion: Our study provides valuable insight into the health-enhancing properties of HMOs while highlighting the need for future research into the efficacy of incorporating individual structures into infant formula, particularly when aiming to modulate the gut microbiota. DLoTGpXbSBXfYGWsHwkdt7 Video Abstract [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) has experienced a steady increase in global incidence and prevalence recently. Current research into UC pathogenesis focuses on the complex interplay of genetic and environmental factors with the immune system and gut microbiome, leading to disruption of the intestinal barrier. Normally, the microbiome, intestinal epithelium, and immune system interact to maintain intestinal homeostasis. However, when this equilibrium is disturbed, a harmful cycle of dysbiosis, immune dysregulation, and inflammation emerges, resulting in intestinal barrier dysfunction and UC progression. Among various risk factors, diet significantly influences epithelial barrier integrity and architectural stability through both direct and indirect mechanisms, shaping the entire UC continuum from pre-clinical prevention to active phase treatment and remission maintenance. This review provides insights into the impact of dietary content and eating behaviors on UC, focusing on specific food, food groups, nutrients, and intermittent fasting, while providing a detailed explanation of why the gut microbiota may mediate the sustained effects of diet across all stages of UC. Additionally, it addresses the limitations of current studies, explores underexamined areas in UC dietary research and proposes potential directions for future research and expansion. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Female infertility is a multifactorial condition influenced by various genetic, environmental, and lifestyle factors. Recent research has investigated the significant impact of gut microbiome dysbiosis on systemic inflammation, metabolic dysfunction, and hormonal imbalances, which can potentially impair fertility. The gut-brain axis, a bidirectional communication system between the gut and the brain, also plays a significant role in regulating reproductive functions. Emerging evidence suggests that the gut microbiome can influence brain functions and behavior, further emphasizing the importance of the microbiota-gut-brain axis in reproduction. Given their role as a major modulator of the gut microbiome, diet and dietary factors, including dietary patterns and nutrient intake, have been implicated in the development and management of female infertility. Hence, this review aims to highlight the impact of dietary patterns, such as the Western diet (WD) and Mediterranean diet (MD), and to decipher their modulatory action on the microbiota-gut-brain axis in infertile women. By contrasting the detrimental effects of WD with the therapeutic potential of MD, we emphasize the pivotal role of a balanced diet rich in nutrients in promoting a healthy gut microbiome. These insights underscore the potential of targeted dietary interventions and lifestyle modifications as promising strategies to enhance reproductive outcomes in subfertile women. [ABSTRACT FROM AUTHOR]

Introduction: Bacterial vaginosis (BV) is one of the most common genital tract infections among women of reproductive age. The existence of BV among pregnant women has momentously attracted the attention of both clinicians and the scientific community due to its potential link with adverse clinical outcomes in pregnancy. Methods: To evaluate the prevalence, risk factors, and adverse outcomes of bacterial vaginosis among pregnant women, a comprehensive systematic review was conducted based on the preferred reporting items for systematic review and meta-analyses (PRISMA) criteria. PubMed, ScienceDirect, ClinicalTrials.gov and Cochrane database searches were conducted independently by two authors until May 13th, 2023. Results: The search strategies yielded a total of 2237 records; among them, 12 studies met the inclusion criteria and were included in the qualitative synthesis. Majority of the included studies demonstrated a high prevalence of BV among African women. The risk of developing BV during pregnancy was highest among women with multiple sexual partners. Additionally, factors including age, socioeconomic status, unhygienic practices, ethnicity, 2nd trimester, spontaneous abortion, vaginal douching, symptoms, and history of sexually transmitted infections (STIs) were also associated with a higher prevalence of BV. Overall, 7 studies reported adverse outcomes during pregnancy which was directly associated with BV. Based on the review, it was found that PROM, PTB, and LBW were the most frequently reported adverse outcomes in pregnant women with BV. Conclusion: In summary, the high prevalence of bacterial vaginosis necessitates a global surveillance approach to delineate the health risks imposed on both mother and child, and promote cost-effective strategic measures to alleviate the undesired consequences of BV during pregnancy. [ABSTRACT FROM AUTHOR]

Autophagic activation in immune cells, gut microbiota dysbiosis, and metabolic abnormalities have been reported separately as characteristics of systemic lupus erythematosus (SLE). Elucidating the crosstalk among the immune system, commensal microbiota, and metabolites is crucial to understanding the pathogenesis of autoimmune diseases. Emerging evidence shows that basophil activation plays a critical role in the pathogenesis of SLE; however, the underlying mechanisms remain largely unknown. Here, we investigated the effects of autophagic inhibition on the pathogenesis of basophils in SLE using Autophagy-related gene 5 (Atg5) knockout (Atg5−/−) as an autophagic inhibitor. Specifically, we knocked out basophilic Atg5 in vivo to investigate its impact on lupus metabolism. Furthermore, Atg5−/− basophils were transferred to basophil-depleted MRL/MpJ-Faslpr (MRL/lpr) mice to study their effect on disease metabolism. Metagenomic and targeted metabolomic sequencing results indicated considerable reduction in the levels of plasma autoantibodies and inflammatory cytokines in the Atg5−/− basophil transfer group compared with that in the control group. Transplanting Atg5−/− basophils improved the gut microbiota balance in MRL/lpr mice, increasing the abundance of beneficial bacteria, such as Ligilactobacillus murinus and Faecalitalea rodentium, and reducing that of potentially pathogenic bacteria such as Phocaeicola salanitronis. The transplantation of Atg5-deficient basophils improved lupus symptoms by modulating lipid and amino acid metabolism. This improvement was linked to changes in the gut microbiota, particularly an increase in Ligilactobacillus murinus and Faecalitalea rodentium populations. These microbial shifts are believed to promote the production of beneficial metabolites, such as γ-linolenic acid and oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine, while reducing the levels of harmful metabolites such as arginine. These alterations in the metabolic profile contribute to the alleviation of lupus symptoms. Collectively, these findings reveal a novel role of basophil autophagy in SLE, highlighting its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The oral cavity is a complex environment which harbours the second largest and most diverse microflora after the gastrointestinal tract. The bacteriome in the oral cavity plays a pivotal role in promoting the health and well-being of human beings. Gingivitis, an inflammation of the gingival tissue, arises due to plaque accumulation on the teeth, often leads to periodontitis. Progression of periodontitis resulting in clinical attachment loss, bone loss and eventually the tooth loss is poorly understood. The present study explores the transitions in microbioata, oxidative stress and polyamine levels during the disease evolution which can contribute to developing effective therapeutic approaches. Methods: Saliva samples were collected from seventy-two individuals after procuring informed consent who were either healthy, gingivitis or stage-specific periodontitis patients. Periodontitis stage was confirmed by clinical and radiographic analysis. Microbiota analysis was carried out by 16S rRNA sequencing on the Nanopore PromethIONsystem platform of Oxford Nanopore technologies. Polyamine levels were quantified with fluorescence spectrophotometer. Ornithine decarboxylase quantification was evaluated by ELISA method. Antioxidant levels of the salivary samples were measured by DPPH, SOD, and catalase assays. Autophagy was measured by acid phosphatase assay. Result: The salivary microbiota exhibited significant changes in their abundance and diversity between healthy individuals and those with conditions such as gingivitis, and chronic periodontitis. A significant increase in polyamines and ornithine decarboxylase was found in gingivitis and various stages of periodontitis. Elevated oxidative stress observed in gingivitis and periodontitis could have resulted in cell death. Conclusion: The current study shows the role of salivary microbiota and polyamines in gingivitis and different periodontitis stages. The progressive elevation of Streptococcus levels from gingivitis to periodontitis, coupled with polyamine concentrations, may serve as a promising identification marker for assessing the severity of periodontal disease. Insight into the oral bacterial flora and associated physiological changes provide a foundation for targeted therapeutic interventions in gingivitis and periodontitis diseases emphasising the importance of personalised oral health management strategies. [ABSTRACT FROM AUTHOR]

Background: Toothache is a debilitating condition, often with mild to excruciating pain, swelling, eating difficulties and insomnia. This study aims to delineate the profiles of patients seeking emergency dental care, focusing on the diagnosis, treatment, and outcomes following non-surgical root canal treatment. Methods: This prospective cohort study was conducted from 2012 to 2021 at the Section for Endodontics, Department of Clinical Dentistry, University of Bergen, Norway. A total of 281 emergency patient forms were analyzed. Data registered included patient demographics, dental history, chief complaints, medications used, diagnostic results, treatments provided and outcome. Results: A total of 272 patients (272 teeth) were included in the study. Pain was the predominant complaint (98.5%), where only 57.4% of the patients managed to localize pain to a specific tooth. The mean age of patients was 51.2 years with no significant gender differences. The maxillary right first molar (15.4%) was the most frequent tooth needing treatment. The majority of the patients had experienced pain for three days before they attended the emergency appointment. The most frequently used drug for pain management was paracetamol which was stated to have little effect. Teeth that needed endodontic treatment often had restorations rather than caries. The most frequent diagnoses were pulpitis (26.8%) followed by necrotic pulp (25.4%) and previously root filled teeth (22.8%). Root canal treatment was performed on 60% of the teeth and a success rate of 95% was registered at one-year recall. Conclusions: There was no singular diagnostic cause leading patients to seek an emergency appointment, highlighting the necessity of a thorough diagnostic procedure. Over the counter pain medications have little effect on alleviating dental pain, often resulting in desperate measures of self-medication. 60% of the teeth needing emergency treatment had previous coronal restorations such as fillings or crowns, indicating that conservative treatment does not appear to fully protect against future pulpal disease. The good prognosis of root canal treatment for teeth with acute symptoms supports recommending dentists to attempt root canal treatment rather than opting for tooth extraction. [ABSTRACT FROM AUTHOR]

Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis—an imbalance in the microbiome—leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges. [ABSTRACT FROM AUTHOR]

Background: Liuweizhiji Gegen-Sangshen oral liquid (LGS), as a Chinese medicinal preparation, is developed from a Traditional Chinese medicinal formula consisting of six Chinese medicinal herbs, including Puerariae lobatae radix, Hoveniae semen, Imperatae rhizoma, Crataegi fructus, Mori fructus and Canarli fructus, and has been extensively utilized in the prevention and treatment of alcoholic liver disease (ALD) clinically. Previous study has demonstrated that LGS dose-dependently mitigated ALD in rat models. However, whether and how the main characteristic constituents of LGS (the flavonoid and polysaccharide fractions, LGSF and LGSP) contribute to the anti-ALD effect remains unclear. This study aimed to assess the anti-ALD effect of LGS and its main fractions (LGSF and LGSP) in a murine model of ALD and to explore the underlying mechanisms. Methods: ALD mouse model was constructed using the chronic and binge ethanol feeding method. Biochemical determinations of AST, ALT, TC, TG, ADH, ALDH, HDL, LDL, IL-1β, IL-6, and TNF-α were performed using corresponding kits. Histopathological examination of liver and intestinal sections was conducted based on the H&E staining. Lipid accumulation in hepatocytes was evaluated by oil red O staining. Ethanol metabolism was assessed by determining the activity of ADH and ALDH enzymes. Intestinal barrier function was analyzed based on immunohistochemistry analysis of ZO-1 and occludin and immunofluorescence analysis of epithelial markers, Lgr5, Muc2, and Lyz1. Intestinal epithelial apoptosis was detected by TUNEL staining. Mouse fecal microbiota alterations were analyzed by 16S rRNA sequencing. An in vitro epithelial injury model was established by developing TNF-α-induced 3D-cultured intestinal organoids. In vitro culture of specific bacterial strains was performed. Results: The results showed that LGS and its flavonoid and polysaccharide fractions (LGSF and LGSP) significantly alleviated ALD in mice through attenuating hepatic injury and inflammation, improving liver steatosis and promoting ethanol metabolism. Notably, LGS, LGSP, and LGSF mitigated intestinal damage and maintained barrier function in ALD mice. The intestinal barrier protection function of LGS, LGSP, and LGSF was generally more obvious than that of the positive drug meltadosine. Further study demonstrated that LGS, LGSP, and LGSF promoted intestinal epithelial repair via promoting Lgr5+ stem cell mediated regeneration in TNF-α-induced intestinal organoids. LGS and LGSF, other than LGSP, had a better effect on repair of epithelial injury in vitro. Moreover, LGS, LGSP, and LGSF remarkably alleviated gut dysbiosis in ALD mice via at least partially recovery of alcohol-induced microbial changes and induction of specific bacterial groups. In vitro culture of bacterial strains indicated that LGS, LGSP, and LGSF had a specific impact on bacterial growth. LGS and LGSP, but not the LGSF, significantly promoted the growth of Lactobacillus. Similarly, LGS and LGSP significantly increased the proliferation of Bacteroides sartorii, and LGSF had a minimal effect. LGS, LGSP and LGSF all promoted the growth of Bacillus coagulans, Bifidobacterium adolescentis, and Bifidobacterium bifidum. LGS and LGSP promoted the growth of Dubosiella newyorkensis, but the LGSF had no effect. Conclusions: LGS exerts its anti-ALD effect in mice through regulating gut-liver axis, and its flavonoid and polysaccharide fractions, LGSF and LGSP, are responsible for its protective effect. [ABSTRACT FROM AUTHOR]

Background: Less than one-third of sub-Saharan Africans have access to improved water sources. In US, Indian, and African studies, Bacterial vaginosis (BV) is increased among women with poor water, sanitation, and hygiene (WASH). We examined water source, sanitation (latrine type), and rainfall in relation to the vaginal microbiome (VMB). Methods: In a cluster randomized controlled trial of menstrual cups and cash transfer, we measured the impact of cups on VMB via 16S rRNA gene amplicon sequencing in a subset of 436 adolescent girls. We analyzed how self-reported water source and latrine type at home related to VMB over 18-months, examining community state type I (CST-I, L. crispatus dominant) vs. other CST; alpha diversity; targeted taxa (coliform and other water-related pathogens); and non-targeted taxa via machine learning approaches. Mixed effects multivariable longitudinal models were adjusted for intervention arm, age, socioeconomic status, sexual activity, and cluster-level school WASH and rainfall (in millimeters). Results: Adjusting for all covariates in all models: (1) the odds of CST-I were increased among participants with piped water (vs. pond), and decreased with traditional pit latrine vs. flush toilet. (2) Alpha diversity varied by water source and latrine type without consistent trends. (3) Coliform bacteria relative abundance (RA) was higher among participants with traditional pit or ventilated improved pit latrines vs. flush toilet, and higher among participants relying on stream vs. pond water. Streptococcus agalactiae RA was higher among participants with non-flush toilets, while Bacteroides fragilis RA was lower with non-flush toilets. (4) Key taxa from non-targeted analyses associated with water source and latrine type included typical vaginal bacteria, opportunistic pathogens, and urinary tract pathobionts. (6) Increased rainfall was associated with decreased odds of CST-I. Trial registration: ClinicalTrials.gov NCT03051789, February 14, 2017. [ABSTRACT FROM AUTHOR]

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Background Bacteroides spp. form a significant part of our gut microbiome and are well known for optimized metabolism of diverse polysaccharides. Initial analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172 glycosyl hydrolases and a large number of uncharacterized proteins associated with polysaccharide metabolism. Results BT_1012 from Bacteroides thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a large protein family consisting entirely of uncharacterized proteins. Initial sequence analysis predicted that this protein has two domains, one on the N- and one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90 half size homologs consisting only of the N-terminal domain. The experimentally determined three-dimensional structure of the BT_1012 protein confirms its two-domain architecture and structural analysis of both domains suggests their specific functions. The N-terminal domain is a putative catalytic domain with significant similarity to known glycoside hydrolases, the C-terminal domain has a beta-sandwich fold typical found in C-terminal domains of other glycosyl hydrolases, however these domains are typically involved in substrate binding. We describe the structure of the BT_1012 protein and discuss its sequence-structure relationship and their possible functional implications. Conclusions Structural and sequence analyses of the BT_1012 protein identifies it as a glycosyl hydrolase, expanding an already impressive catalog of enzymes involved in polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the Pfam families representing the two domains found in the BT_1012 protein, PF13204 and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C-terminal domain respectively. [ABSTRACT FROM AUTHOR]

Background The liver is the first line of defence against continuously occurring influx of microbialderived products and bacteria from the gut. Intestinal bacteria have been implicated in the pathogenesis of alcoholic liver cirrhosis. Escape of intestinal bacteria into the ascites is involved in the pathogenesis of spontaneous bacterial peritonitis, which is a common complication of liver cirrhosis. The association between faecal bacterial populations and alcoholic liver cirrhosis has not been resolved Methods Relative ratios of major commensal bacterial communities (Bacteroides spp., Bifidobacterium spp., Clostridium leptum group, Enterobactericaea and Lactobacillus spp.) were determined in faecal samples from post mortem examinations performed on 42 males, including cirrhotic alcoholics (n = 13), non-cirrhotic alcoholics (n = 15), non-alcoholic controls (n = 14) and in 7 healthy male volunteers using real-time quantitative PCR (RTqPCR). Translocation of bacteria into liver in the autopsy cases and into the ascites of 12 volunteers with liver cirrhosis was also studied with RT-qPCR. CD14 immunostaining was performed for the autopsy liver samples. Results Relative ratios of faecal bacteria in autopsy controls were comparable to those of healthy volunteers. Cirrhotics had in median 27 times more bacterial DNA of Enterobactericaea in faeces compared to the healthy volunteers (p = 0.011). Enterobactericaea were also the most common bacteria translocated into cirrhotic liver, although there were no statistically significant differences between the study groups. Of the ascites samples from the volunteers with liver cirrhosis, 50% contained bacterial DNA from Enterobactericaea, Clostridium leptum group or Lactobacillus spp.. The total bacterial DNA in autopsy liver was associated with the percentage of CD14 expression (p = 0.045). CD14 expression percentage in cirrhotics was significantly higher than in the autopsy controls (p = 0.004). Conclusions Our results suggest that translocation of intestinal bacteria into liver may be involved as a one factor in the pathogenesis of alcoholic liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Anaerobes are normal flora of the human body. However, they can cause serious infections in humans. Anaerobic bacteria are known to cause respiratory infections like pneumonia and acute exacerbation of chronic lower airway infections. These are often missed due to the complexity of their isolation and identification. Hence, this study aimed to study anaerobes causing respiratory tract infections and determine their antibiotic susceptibility., Materials & Methods: Clinical specimens such as bronchial aspirates and pleural aspirates collected from patients with respiratory diseases attending Vallabhbhai Patel Chest Institute were processed, the anaerobes isolated were identified, and their susceptibilities to various groups of antimicrobials were studied using standard microbiological methods., Results: Three hundred and fourteen patients were included in the study, 154 males and 160 females. Of these 314 patients, 148 (47%) yielded anaerobes in their clinical samples. Seventy patients had more than one type of anaerobic organism. Hence, 235 isolates were recovered belonging to as many as 17 genera. The MIC of seven antibiotics on 154 isolates was tested. The isolates belonged mostly to the genera Bacteroides, Prevotella, Veillonella, and Actinomyces. Variable resistance was observed to most classes of antibiotics by many genera., Conclusions: Metronidazole is commonly used against anaerobes, but the study showed that the isolates were 20-30% resistant to the antibiotic. Starting this as an empirical therapy might lead to treatment failure., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The rapid establishment and persistence of latent HIV-1 reservoirs is one of the main obstacles towards an HIV cure. While antiretroviral therapy supresses viral replication, it does not eradicate the latent reservoir of HIV-1-infected cells. Recent evidence suggests that the human microbiome, particularly the gut microbiome, may have the potential to modulate the HIV-1 reservoir. However, literature is limited and the exact mechanisms underlying the role of the microbiome in HIV immunity and potential regulation of the viral reservoir remain poorly understood. Results: Here, we review updated knowledge on the associations between the human microbiome and HIV reservoir across different anatomical sites, including the gut, the lungs and blood. We provide an overview of the predominant taxa associated with prominent microbiome changes in the context of HIV infection. Based on the current evidence, we summarize the main study findings, with specific focus on consistent bacterial and related byproduct associations. Specifically, we address the contribution of immune activation and inflammatory signatures on HIV-1 persistence. Furthermore, we discuss possible scenarios by which bacterial-associated inflammatory mediators, related metabolites and host immune signatures may modulate the HIV reservoir size. Finally, we speculate on potential implications of microbiome-based therapeutics for future HIV-1 cure strategies, highlighting challenges and limitations inherent in this research field. Conclusions: Despite recent advances, this review underscores the need for further research to deepen the understanding of the complex interplay between the human microbiome and HIV reservoir. Further integrative multi-omics assessments and functional studies are crucial to test the outlined hypothesis and to identify potential therapeutic targets ultimately able to achieve an effective cure for HIV. [ABSTRACT FROM AUTHOR]

Saccharomyces boulardii (S. boulardii) is a fungal probiotic used to treat digestive disorders. However, the mechanism(s) by which S. boulardii affects the small intestine remains unclear. Here, we aimed to explore the effects of S. boulardii on the small intestine and the underlying mechanisms in mice with loperamide-induced constipation. While S. boulardii administration did not fully reverse the alterations in loperamide-induced defecation parameters, it altered the small intestinal floral composition toward a community conducive to alleviate constipation. Moreover, S. boulardii up-regulated the expression of tyrosine-protein kinase Kit (c-Kit), aquaporin 3 (AQP3), interleukin (IL)-10, myosin light chain kinase (MLCK), and phosphorylated myosin light chain 20 (P-MLC20), while concurrently down-regulating the expression levels of inducible nitric oxide synthase (iNOS), p65, and IL-17 A. These alterations indicate a discernible effect of small intestinal water reabsorption, inflammatory factor levels, and smooth muscle contraction. Saccharomyces boulardii also positively regulated small intestinal metabolite levels, such as fructose 6-phosphate, dihomo-alpha-linolenic acid, and 3-(4-hydroxyphenyl) lactate, and participated in metabolic pathways such as arginine biosynthesis, linoleic acid metabolism, and protein digestion and absorption. While not fully reversing defecation changes, Saccharomyces boulardii alters intestinal flora, up-regulates key proteins affecting water reabsorption and inflammation, and positively influences metabolic pathways. Our study provides serves as a basis for further studies on the application of S. boulardii in the treatment of intestinal disorders. [ABSTRACT FROM AUTHOR]

Background: Aflatoxin B1 (AFB1) is a mycotoxin that widely found in the environment and mouldy foods. AFB1 initially targets the intestine, and AFB1-induced intestinal injury cannot be ignored. Lactobacillus amylovorus (LA), a predominant species of Lactobacillus, plays a role in carbohydrate metabolism. Extracellular vesicles (EVs), small lipid membrane vesicles, are widely involved in diverse cellular processes. However, the mechanism by which Lactobacillus amylovorus-QC1H-derived EVs (LA.EVs) protect against AFB1-induced intestinal injury remains unclear. Results: In our study, a new strain named Lactobacillus amylovorus-QC1H (LA-QC1H) was isolated from pig faeces. Then, EVs derived from LA-QC1H were extracted via ultracentrifugation. Our results showed that LA.EVs significantly alleviated AFB1-induced intestinal injury by inhibiting the production of proinflammatory cytokines, decreasing intestinal permeability and increasing the expression of tight junction proteins. Moreover, 16 S rRNA analysis revealed that LA.EVs modulated AFB1-induced gut dysbiosis in mice. However, LA.EVs did not exert beneficial effects in antibiotic-treated mice. LA.EVs treatment increased intestinal levels of indole-3-acetic acid (IAA) and activated intestinal aryl hydrocarbon receptor (AHR)/interleukin-22 (IL-22) signalling in AFB1-exposed mice. Inhibition of intestinal AHR signalling markedly weakened the protective effect of LA.EVs in AFB1-exposed mice. Conclusions: LA.EVs alleviated AFB1-induced intestinal injury by modulating the gut microbiota, activating the intestinal AHR/IL-22 signalling, reducing the inflammatory response and promoting intestinal barrier repair in mice. [ABSTRACT FROM AUTHOR]

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium. [ABSTRACT FROM AUTHOR]

Background: Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbiosis. However, it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets. Results: In this study, we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score, and elevated levels of lipopolysaccharide (LPS) and D-lactate (D-LA) compared to healthy piglets. Subsequently, we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets. Diarrheal piglets demonstrated intestinal microbiota dysbiosis, characterized primarily by a higher Firmicutes to Bacteroidota ratio, a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri, and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron. Functional profiling of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data was performed, and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diarrhea. Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets. Furthermore, we explored the effects of dietary indole-3-aldehyde (IAld), a key tryptophan metabolite, on intestinal development and gut barrier function in weaned piglets. Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell (ISC) expansion in piglets. The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids. Conclusions: These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intestinal development by promoting ISC expansion in weaned piglets. [ABSTRACT FROM AUTHOR]

Probiotic extracellular vesicles (pEVs) are biologically active nanoparticle structures that can regulate the intestinal tract through direct or indirect mechanisms. They enhance the intestinal barrier function in livestock and poultry and help alleviate intestinal diseases. The specific effects of pEVs depend on their internal functional components, including nucleic acids, proteins, lipids, and other substances. This paper presents a narrative review of the impact of pEVs on the intestinal barrier across various segments of the intestinal tract, exploring their mechanisms of action while highlighting the limitations of current research. Investigating the mechanisms through which probiotics operate via pEVs could deepen our understanding and provide a theoretical foundation for their application in livestock production. [ABSTRACT FROM AUTHOR]

The recent emergence of Elizabethkingia anophelis as a human pathogen is a major concern for global public health. This organism has the potential to cause severe infections and has inherent antimicrobial resistance. The potential for widespread outbreaks and rapid global spread highlights the critical importance of understanding the biology and transmission dynamics of this infectious agent. We performed a large-scale analysis of available 540 E. anophelis, including one novel strain isolated from raw milk and sequenced in this study. Pan-genome analysis revealed an open and diverse pan-genome in this species, characterized by the presence of many accessory genes. This suggests that the species has a high level of adaptability and can thrive in a variety of environments. Phylogenetic analysis has also revealed a complex population structure, with limited source-lineage correlation. We identified diverse antimicrobial resistance factors, including core-genome and accessory ones often associated with mobile genetic elements within specific lineages. Mobilome analysis revealed a dynamic landscape primarily composed of genetic islands, integrative and conjugative elements, prophage elements, and small portion of plasmids emphasizing a complex mechanism of horizontal gene transfer. Our study underscores the adaptability of E. anophelis, characterized by a diverse range of antimicrobial resistance genes, putative virulence factors, and genes enhancing fitness. This adaptability is also supported by the organism's ability to acquire genetic material through horizontal gene transfer, primarily facilitated by mobile genetic elements such as integrative and conjugative elements (ICEs). The potential for rapid evolution of this emerging pathogen poses a significant challenge to public health efforts. [ABSTRACT FROM AUTHOR]

Background: Alterations in upper respiratory microbiomes have been implicated in shaping host health trajectories, including by limiting mucosal pathogen colonization. However, limited comparative studies of respiratory microbiome development and functioning across age groups have been performed. Herein, we perform shotgun metagenomic sequencing paired with pathogen inhibition assays to elucidate differences in nasal and oral microbiome composition and intermicrobial interactions across healthy 24-month-old infant (n = 229) and adult (n = 100) populations. Results: We find that beta diversity of nasal and oral microbiomes varies with age, with nasal microbiomes showing greater population-level variation compared to oral microbiomes. Infant microbiome alpha diversity was significantly lower across nasal samples and higher in oral samples, relative to adults. Accordingly, we demonstrate significant differences in genus- and species-level composition of microbiomes between sites and age groups. Antimicrobial resistome patterns likewise varied across body sites, with oral microbiomes showing higher resistance gene abundance compared to nasal microbiomes. Biosynthetic gene clusters encoding specialized metabolite production were found in higher abundance across infant oral microbiomes, relative to adults. Investigation of pathogen inhibition revealed greater inhibition of gram-negative and gram-positive bacteria by oral commensals, while nasal isolates had higher antifungal activity. Conclusions: In summary, we identify significant differences in the microbial communities inhabiting nasal and oral cavities of healthy infants relative to adults. These findings inform our understanding of the interactions impacting respiratory microbiome composition and functions related to colonization resistance, with important implications for host health across the lifespan. 5XcHcd9N21H4_6hqSTf5-o Video Abstract [ABSTRACT FROM AUTHOR]

Background: How to reduce the high incidence rate and mortality of colorectal cancer (CRC) effectively is the focus of current research. Endoscopic treatment of early-stage CRC and colorectal adenomas (CAC) has a high success rate, but although several treatments are available for advanced CRC, such as surgery, radiotherapy, chemotherapy, and immunotherapy, the 5-year survival rate remains low. In view of the high incidence rate and mortality of CRC, early rational drug prevention for high-risk groups and exploration of alternative treatment modalities are particularly warranted. Summary: Gut microbiota is the target of and interacts with probiotics, prebiotics, aspirin, metformin, and various Chinese herbal medicines (CHMs) for the prevention of CRC. In addition, the anti-cancer mechanisms of probiotics differ widely among bacterial strains, and both bacterial strains and their derivatives and metabolites have been found to have anti-cancer effects. Gut microbiota plays a significant role in early drug prevention of CRC and treatment of CRC in its middle and late stages, targeting gut microbiota may be a new strategy for colorectal cancer treatment. Key message: This review covers current progress in the role of gut microbiota and drugs in CRC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most prevalent and lethal malignant tumors globally, posing significant health risks and societal burdens. Recently, advancements in next-generation sequencing technology have identified CRC intratumoral microbiota, thereby opening up novel avenues for further research. This review synthesizes the current advancements in CRC intratumoral microbiota and their impact on CRC progression and discusses the disparities in the relative abundance and community composition of CRC intratumoral microbiota across various colorectal tumors based on their anatomical location and molecular subtypes, as well as the tumor stages, and spatial tumor distribution. Intratumoral microbiota predominantly influence CRC development by modulating colonic epithelial cells, tumor cells, and the tumor microenvironment. Mechanistically, they can cause DNA damage, apoptosis and epithelial-mesenchymal transition. The effects of different intratumoral microbiota on CRC have been shown to be two-fold. In the future, to address the limitations of existing studies, it is important to develop comprehensive experimental protocols and suitable in vitro models for elucidating more mechanisms of intratumoral microbiota on CRC, which will facilitate the clinical application of microbe-related therapeutic strategies in CRC and potentially other tumors. [ABSTRACT FROM AUTHOR]

Scope: The underlying medical conditions and gut dysbiosis is known to influence COVID-19 severity in high-risk patients. The current review proposed the optimal usage of nutraceuticals & pharmacological interventions can help regulate the protective immune response and balance the regulatory functionality of gut microbiota. Summary: Many studies have revealed that the probiotic interventions viz., Lactobacillus rhamnosus, L. plantarum & other bacterial spp. reduce IFNγ & TNF-α and increase IL-4 & IL-10 secretions to control the immunostimulatory effects in upper respiratory tract infection. Dietary fibres utilized by beneficial microbiota and microbial metabolites can control the NF-kB regulation. Vitamin C halts the propagation of pathogens and vitamin D and A modulate the GM. Selenium and Flavonoids also control the redox regulations. Interferon therapy can antagonize the viral replications, while corticosteroids may reduce the death rates. BCG vaccine reprograms the monocytes to build trained immunity. Bifidobacterium and related microbes were found to increase the vaccine efficacy. Vaccines against COVID-19 and season flu also boost the immunity profile for robust protection. Over all, the collective effects of these therapeutics could help increase the opportunities for faster recovery from infectious diseases. Conclusion: The nutraceutical supplements and pharmacological medicines mediate the modulatory functionalities among beneficial microbes of gut, which in turn eliminate pathogens, harmonize the activity of immune cells to secrete essential regulatory molecular receptors and adaptor proteins establishing the homeostasis in the body organs through essential microbiome. Therefore, the implementation of this methodology could control the severity events during clinical sickness and reduce the mortalities. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention, especially in the context of alternative feeding strategies. This study aims to elucidate the effects of milk replacer (MR) feeding on growth, lipid metabolism, colonic epithelial gene expression, colonic microbiota composition and systemic metabolism in goat kids compared to breast milk (BM) feeding, addressing a critical knowledge gap in early life nutrition. Methods: Ten female goat kids were divided into 2 groups: those fed breast milk (BM group) and those fed a milk replacer (MR group). Over a period of 28 d, body weight was monitored and blood and tissue samples were collected for biochemical, transcriptomic and metabolomic analyses. Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing. Intestinal microbiota transplantation (IMT) experiments in gnotobiotic mice were performed to validate causality. Results: MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol (TC) and non-esterified fatty acid (NEFA) concentrations. Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism, concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria. Specifically, genera such as Bifidobacterium and Prevotella were enriched in the MR group, while Clostridium and Faecalibacterium were depleted. Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic pathways. IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats, confirming the role of the microbiota in modulating host lipid metabolism. Conclusions: Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics, resulting in reduced growth rates and metabolic alterations. These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants. This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity. [ABSTRACT FROM AUTHOR]

Background: Cationic antibacterial peptides (CAPs) and synthetic molecules mimicking the amphiphilic structure of CAPs, such as ceragenins, are promising compounds for the development of new antimicrobials. Results: We tested the in vitro activity of ceragenins CSA-13 and CSA-131 against several anaerobic bacteria including Bacteroides spp. and Clostridium difficile. We compared results to the activity of cathelicidin LL-37, metronidazole and nanosystems developed by attachment of CSA-13 and CSA-131 to magnetic nanoparticles (MNPs). The antibacterial effect was tested using killing assay and modified CLSI broth microdilution assay. Ceragenins CSA-13 and CSA-131 displayed stronger bactericidal activity than LL-37 or metronidazole against all of the tested bacterial strains. Additionally CSA-131 revealed an enhanced ability to prevent the formation of Bacteroides fragilis and Propionibacterium acnes biofilms. Conclusions: These data confirmed that ceragenins display antimicrobial activity against a broad range of microorganisms including anaerobic bacteria and deserve further investigations as compounds serving to develop new treatment against anaerobic and mixed infections. [ABSTRACT FROM AUTHOR]

Background: While significant research exists on gut microbiota changes after anti-tumor necrosis factor-alpha (anti TNF-α) therapy for ulcerative colitis, little is known about the longitudinal changes related to the effects of anti TNF-α. This study aimed to investigate the dynamics of gut microbiome changes during anti TNF-α (adalimumab) therapy in patients with ulcerative colitis (UC). Results: The microbiota composition was affected by the disease severity and extent in patients with UC. Regardless of clinical remission status at each time point, patients with UC exhibited microbial community distinctions from healthy controls. Distinct amplicon sequence variants (ASVs) differences were identified throughout the course of Adalimumab (ADA) treatment at each time point. A notable reduction in gut microbiome dissimilarity was observed only in remitters. Remitters demonstrated a decrease in the relative abundances of Burkholderia-Caballeronia-Paraburkholderia and Staphylococcus as the treatment progressed. Additionally, there was an observed increase in the relative abundances of Bifidobacterium and Dorea. Given the distribution of the 48 ASVs with high or low relative abundances in the pre-treatment samples according to clinical remission at week 8, a clinical remission at week 8 with a sensitivity and specificity of 72.4% and 84.3%, respectively, was predicted on the receiver operating characteristic curve (area under the curve, 0.851). Conclusions: The gut microbiota undergoes diverse changes according to the treatment response during ADA treatment. These changes provide insights into predicting treatment responses to ADA and offer new therapeutic targets for UC. [ABSTRACT FROM AUTHOR]

Background: The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota. Astragalus polysaccharides (APS) have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function. The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed. Results: Dietary polysaccharide deprivation induced intestinal barrier dysfunction, decreased growth performance, altered microbial composition (Faecalibacterium, Dorea, and Coprobacillus), and reduced isobutyrate concentration. The results showed that APS facilitates intestinal barrier function in broiler chickens, including a thicker mucus layer, reduced crypt depth, and the growth of tight junction proteins. We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides, a commensal bacterium that plays a predominant role in enhancing intestinal barrier function. An in vitro growth assay further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis. Dietary APS supplementation increased the concentrations of isobutyrate and bile acid (mainly chenodeoxycholic acid and deoxycholate acid) and activated signaling pathways related to intestinal barrier function (such as protein processing in the endoplasmic reticulum, tight junctions, and adherens junction signaling pathways). Conclusions: APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis, and increasing the concentrations of isobutyrate and bile acids (mainly CDCA and DCA). These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function. [ABSTRACT FROM AUTHOR]

Objective: The health of oral cavity is considered as an important indicator of aging. Oral microbiota is highly associated with the oral health, while the variation of oral microbiome in elderly population and characteristic microbes associated with aging remain unclear. Subjects and methods: In this study, 130 elderly subjects were recruited and divided into 3 groups according to their age: Stage I group (65 ≤ years < 70), Stage II group (70 ≤ years < 75), and Stage III group (75 ≤ years < 80). Their physiological indices were analyzed with using Illumina MiSeq platform and the oral microbiome was determined by high-throughput sequencing. Results: Along with aging, the level of fasting blood glucose, systolic pressure and monocytes are significantly increased. No significant difference was detected on the whole structure of the oral microbiome among groups. While using Metastats and Spearman's correlation analysis, specific bacteria were identified as potential age- or health index-related bacterial genera including Fusobacterium, Parvimonas, Porphyromonas, Aminobacter, Collinsella, Clostridium and Acinetobacter. Conclusion: Our study revealed that the composition structure of salivary microbiota in elderly population was relatively stable while specific bacteria were correlated with age and health status, which is promising to be served as health indicators of the elderly after further exploration. [ABSTRACT FROM AUTHOR]

Background: As a nexus of routine antibiotic use and zoonotic pathogen presence, the livestock farming environment is a potential hotspot for the emergence of zoonotic diseases and antibiotic resistant bacteria. Livestock can further facilitate disease transmission by serving as intermediary hosts for pathogens before a spillover event. In light of this, we aimed to characterize the microbiomes and resistomes of dairy workers, whose exposure to the livestock farming environment places them at risk for facilitating community transmission of antibiotic resistant genes and emerging zoonotic diseases. Results: Using shotgun sequencing, we investigated differences in the taxonomy, diversity and gene presence of 10 dairy farm workers and 6 community controls' gut metagenomes, contextualizing these samples with additional publicly available gut metagenomes. We found no significant differences in the prevalence of resistance genes, virulence factors, or taxonomic composition between the two groups. The lack of statistical significance may be attributed, in part, to the limited sample size of our study or the potential similarities in exposures between the dairy workers and community controls. We did, however, observe patterns warranting further investigation including greater abundance of tetracycline resistance genes and prevalence of cephamycin resistance genes as well as lower average gene diversity (even after accounting for differential sequencing depth) in dairy workers' metagenomes. We also found evidence of commensal organism association with tetracycline resistance genes in both groups (including Faecalibacterium prausnitzii, Ligilactobacillus animalis, and Simiaoa sunii). Conclusions: This study highlights the utility of shotgun metagenomics in examining the microbiomes and resistomes of livestock workers, focusing on a cohort of dairy workers in the United States. While our study revealed no statistically significant differences between groups in taxonomy, diversity and gene presence, we observed patterns in antibiotic resistance gene abundance and prevalence that align with findings from previous studies of livestock workers in China and Europe. Our results lay the groundwork for future research involving larger cohorts of dairy and non-dairy workers to better understand the impact of occupational exposure to livestock farming on the microbiomes and resistomes of workers. [ABSTRACT FROM AUTHOR]

Background: Natural compounds can positively impact health, and various studies suggest that they regulate glucose‒lipid metabolism by influencing short-chain fatty acids (SCFAs). This metabolism is key to maintaining energy balance and normal physiological functions in the body. This review explores how SCFAs regulate glucose and lipid metabolism and the natural compounds that can modulate these processes through SCFAs. This provides a healthier approach to treating glucose and lipid metabolism disorders in the future. Methods: This article reviews relevant literature on SCFAs and glycolipid metabolism from PubMed and the Web of Science Core Collection (WoSCC). It also highlights a range of natural compounds, including polysaccharides, anthocyanins, quercetins, resveratrols, carotenoids, and betaines, that can regulate glycolipid metabolism through modulation of the SCFA pathway. Results: Natural compounds enrich SCFA-producing bacteria, inhibit harmful bacteria, and regulate operational taxonomic unit (OTU) abundance and the intestinal transport rate in the gut microbiota to affect SCFA content in the intestine. However, most studies have been conducted in animals, lack clinical trials, and involve fewer natural compounds that target SCFAs. More research is needed to support the conclusions and to develop healthier interventions. Conclusions: SCFAs are crucial for human health and are produced mainly by the gut microbiota via dietary fiber fermentation. Eating foods rich in natural compounds, including fruits, vegetables, tea, and coarse fiber foods, can hinder harmful intestinal bacterial growth and promote beneficial bacterial proliferation, thus increasing SCFA levels and regulating glucose and lipid metabolism. By investigating how these compounds impact glycolipid metabolism via the SCFA pathway, novel insights and directions for treating glucolipid metabolism disorders can be provided. [ABSTRACT FROM AUTHOR]

Background : Endometriosis, defined as the presence of endometrial-like tissue outside of the uterus, is one of the most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis is not clear. Novel studies indicate that the gut microbiome may be involved in the etiology of endometriosis; nevertheless, the connection between microbes, their dysbiosis, and the development of endometriosis is understudied. This case–control study analyzed the gut microbiome in women with and without endometriosis to identify microbial targets involved in the disease. Methods: A subsample of 1000 women from the Estonian Microbiome cohort, including 136 women with endometriosis and 864 control women, was analyzed. Microbial composition was determined by shotgun metagenomics and microbial functional pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm was performed to cluster the microbial profile of the Estonian population. The alpha- and beta-diversity and differential abundance analyses were performed to assess the gut microbiome (species and KEGG orthologies (KO)) in both groups. Metagenomic reads were mapped to estrobolome-related enzymes' sequences to study potential microbiome-estrogen metabolism axis alterations in endometriosis. Results: Diversity analyses did not detect significant differences between women with and without endometriosis (alpha-diversity: all p-values > 0.05; beta-diversity: PERMANOVA, both R2 < 0.0007, p-values > 0.05). No differential species or pathways were detected after multiple testing adjustment (all FDR p-values > 0.05). Sensitivity analysis excluding women at menopause (> 50 years) confirmed our results. Estrobolome-associated enzymes' sequence reads were not significantly different between groups (all FDR p-values > 0.05). Conclusions: Our findings do not provide enough evidence to support the existence of a gut microbiome-dependent mechanism directly implicated in the pathogenesis of endometriosis. To the best of our knowledge, this is the largest metagenome study on endometriosis conducted to date. [ABSTRACT FROM AUTHOR]

Background: A parotid abscess (PA) is a complication of an acute bacterial parotitis with a potentially life-threatening course. To date, data on the diagnosis and therapy of PA is sparse and mostly consists of case reports or case series. Therefore, this study aimed at comprehensively analyzing the microbiological spectrum and the therapeutic management in a bi-institutional setting. Methods: A retrospective clinical chart review was performed to identify all patients surgically treated for PA at two tertiary care centers in Germany. Data on demographics, clinical management and microbiological data including species identification, pathogenicity, type of antibiotic therapy, adjustment of antibiotics, antibiotic sensitivity testing, and smear test results were extracted. Intervention-related variables and etiology were analyzed for their statistical association with outcome variables. Results: Overall, 85 patients were included. Most patients (92.9%) underwent surgical incision. Around half of the patients (45.9%) were treated under local anesthesia. No facial nerve palsy was observed. The most frequently detected pathogens were Streptococci (n = 23), followed by Staphylococcus aureus (n = 6) including one case of methicillin-resistant Staphylococcus aureus. Most patients (68.2%) received an aminopenicillin ± beta-lactamase inhibitor as empiric antibiotic therapy. In 6 cases the antibiotic therapy was modified after receiving the antibiogram. Four patients (5.2%) presented with recurrent PA. Etiology was idiopathic (42.4%), followed by tumorous (12.9%), obstructive, and immunosuppressive (each 11.8%). Patients with a dental focus (p = 0.007) had a longer duration of hospitalization. Conclusion: The results show that the surgical therapy of PA under local anesthesia is safe. A dental examination should routinely be performed to rule out a dental focus. Obtaining a microbiological specimen in order to modify antibiotic therapy if necessary and a histopathological specimen to rule out a tumorous etiology is obligate. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota significantly influences the health and growth of red-spotted grouper (Epinephelus akaara), a well-known commercial marine fish from Fujian Province in southern China. However, variations in survival strategies and seasons can impact the stability of gut microbiota data, rendering it inaccurate in reflecting the state of gut microbiota. Which impedes the effective enhancement of aquaculture health through a nuanced understanding of gut microbiota. Inspired by this, we conducted a comprehensive analysis of the gut microbiota of wild and captive E. akaara in four seasons. Results: Seventy-two E. akaara samples were collected from wild and captive populations in Dongshan city, during four different seasons. Four sections of the gut were collected to obtain comprehensive information on the gut microbial composition and sequenced using 16S rRNA next-generation Illumina MiSeq. We observed the highest gut microbial diversity in both captive and wild E. akaara during the winter season, and identified strong correlations with water temperature using Mantel analysis. Compared to wild E. akaara, we found a more complex microbial network in captive E. akaara, as evidenced by increased abundance of Bacillaceae, Moraxellaceae and Enterobacteriaceae. In contrast, Vibrionaceae, Clostridiaceae, Flavobacteriaceae and Rhodobacteraceae were found to be more active in wild E. akaara. However, some core microorganisms, such as Firmicutes and Photobacterium, showed similar distribution patterns in both wild and captive groups. Moreover, we found the common community composition and distribution characteristics of top 10 core microbes from foregut to hindgut in E. akaara. Conclusions: Collectively, the study provides relatively more comprehensive description of the gut microbiota in E. akaara, taking into account survival strategies and temporal dimensions, which yields valuable insights into the gut microbiota of E. akaara and provides a valuable reference to its aquaculture. [ABSTRACT FROM AUTHOR]

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs. [ABSTRACT FROM AUTHOR]

Background: The metabolic disturbances of obesity can be mitigated by strategies modulating the gut microbiota. In this study, we sought to identify whether innate or adaptive immunity mediates the beneficial metabolic effects of the human intestinal bacterium Bacteroides uniformis CECT 7771 in obesity. Methods: We evaluated the effects of orally administered B. uniformis on energy homeostasis, intestinal immunity, hormone levels, and gut microbiota in wild-type and Rag1-deficient mice with diet-induced obesity. We also assessed whether B. uniformis needed to be viable to exert its beneficial effects in obesity and to directly induce immunoregulatory effects. Results: The administration of B. uniformis to obese mice improved glucose tolerance and insulin secretion, restored the caloric intake suppression after an oral glucose challenge, and reduced hyperglycemia. The pre- and post-prandial glucose-related benefits were associated with restoration of the anti-inflammatory tone mediated by type 2 macrophages and regulatory T cells (Tregs) in the lamina propria of the small intestine. Contrastingly, B. uniformis administration failed to improve glucose tolerance in obese Rag1-/- mice, but prevented the increased body weight gain and adiposity. Overall, the beneficial effects seemed to be independent of enteroendocrine effects and of major changes in gut microbiota composition. B. uniformis directly induced Tregs generation from naïve CD4+ T cells in vitro and was not required to be viable to improve glucose homeostasis but its viability was necessary to prevent body weight gain in diet-induced obese wild-type mice. Conclusions: Here we demonstrate that B. uniformis modulates the energy homeostasis in diet-induced obese mice through different mechanisms. The bacterium improves oral glucose tolerance by adaptive immunity-dependent mechanisms that do not require cell viability and prevents body weight gain by adaptive immunity-independent mechanisms which require cell viability. 4U7c4GKqHnKBBCB4_RfnuD Video Abstract [ABSTRACT FROM AUTHOR]

Background: Dietary intake of specific non-digestible carbohydrates (including prebiotics) is increasingly seen as a highly effective approach for manipulating the composition and activities of the human gut microbiota to benefit health. Nevertheless, surprisingly little is known about the global response of the microbial community to particular carbohydrates. Recent in vivo dietary studies have demonstrated that the species composition of the human faecal microbiota is influenced by dietary intake. There is now potential to gain insights into the mechanisms involved by using in vitro systems that produce highly controlled conditions of pH and substrate supply. Results: We supplied two alternative non-digestible polysaccharides as energy sources to three different human gut microbial communities in anaerobic, pH-controlled continuous-flow fermentors. Community analysis showed that supply of apple pectin or inulin resulted in the highly specific enrichment of particular bacterial operational taxonomic units (OTUs; based on 16S rRNA gene sequences). Of the eight most abundant Bacteroides OTUs detected, two were promoted specifically by inulin and six by pectin. Among the Firmicutes, Eubacterium eligens in particular was strongly promoted by pectin, while several species were stimulated by inulin. Responses were influenced by pH, which was stepped up, and down, between 5.5, 6.0, 6.4 and 6.9 in parallel vessels within each experiment. In particular, several experiments involving downshifts to pH 5.5 resulted in Faecalibacterium prausnitzii replacing Bacteroides spp. as the dominant sequences observed. Community diversity was greater in the pectin-fed than in the inulin-fed fermentors, presumably reflecting the differing complexity of the two substrates. Conclusions: We have shown that particular non-digestible dietary carbohydrates have enormous potential for modifying the gut microbiota, but these modifications occur at the level of individual strains and species and are not easily predicted a priori. Furthermore, the gut environment, especially pH, plays a key role in determining the outcome of interspecies competition. This makes it crucial to put greater effort into identifying the range of bacteria that may be stimulated by a given prebiotic approach. Both for reasons of efficacy and of safety, the development of prebiotics intended to benefit human health has to take account of the highly individual species profiles that may result. [ABSTRACT FROM AUTHOR]

Background: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Result: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. Conclusion: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. C3P3Z-i-BEWcsPG8U_9P4f Video Abstract [ABSTRACT FROM AUTHOR]

Background: Gut microbiome metabolites are important modulators of host health and disease. However, the overall metabolic potential of the gut microbiome and interactions with the host organs have been underexplored. Results: Using stable isotope resolved metabolomics (SIRM) in mice orally gavaged with 13C-inulin (a tracer), we first observed dynamic enrichment of 13C-metabolites in cecum contents in the amino acids and short-chain fatty acid metabolism pathways. 13C labeled metabolites were subsequently profiled comparatively in plasma, liver, brain, and skeletal muscle collected at 6, 12, and 24 h after the tracer administration. Organ-specific and time-dependent 13C metabolite enrichments were observed. Carbons from the gut microbiome were preferably incorporated into choline metabolism and the glutamine-glutamate/GABA cycle in the liver and brain, respectively. A sex difference in 13C-lactate enrichment was observed in skeletal muscle, which highlights the sex effect on the interplay between gut microbiome and host organs. Choline was identified as an interorgan metabolite derived from the gut microbiome and fed the lipogenesis of phosphatidylcholine and lysophosphatidylcholine in host organs. In vitro and in silico studies revealed the de novo synthesis of choline in the human gut microbiome via the ethanolamine pathway, and Enterococcus faecalis was identified as a major choline synthesis species. These results revealed a previously underappreciated role for gut microorganisms in choline biosynthesis. Conclusions: Multicompartmental SIRM analyses provided new insights into the current understanding of dynamic interorgan metabolite transport between the gut microbiome and host at the whole-body level in mice. Moreover, this study singled out microbiota-derived metabolites that are potentially involved in the gut-liver, gut-brain, and gut-skeletal muscle axes. 1fG1mJvQp124HCbb2HZFdq Video Abstract [ABSTRACT FROM AUTHOR]