Contribution Of Gut Microbiota Research Articles

The modulation of intestinal commensal bacteria possibly contributes to the growth and immunity promotion in Epinephelus akaara after feeding the antimicrobial peptide Scy-hepc.

Our previous study revealed that feeding the antimicrobial peptide (AMP) product Scy-hepc significantly enhances the growth of mariculture fish through the activation of the GH-Jak2-STAT5-IGF1 axis. However, the contribution of gut microbiota to this growth enhancement remains unclear. This study aimed to elucidate the potential mechanism involved in intestinal absorption and modulation of gut microbiota in Epinephelus akaara following Scy-hepc feeding. The results showed that a 35day regimen of Scy-hpec markedly promoted the growth of E. akaara compared to groups supplemented with either florfenicol, B. subtilis, or a vector. The growth enhancement is likely attributed to alterations in microbiota colonization in the foregut and midgut, characterized by an increasing abundance of potential probiotics (Rhizobiaceae and Lysobacter) and a decreased abundance of opportunistic pathogens (Psychrobacter and Brevundimonas) as determined by 16S rRNA analysis. Additionally, similar to the effect of florfenicol feeding, Scy-hepc significantly improved host survival rate by over 20% in response to a lethal dose challenge with Edwardsiella tarda. Further investigations demonstrated that Scy-hepc is absorbed by the fish foregut (20-40min) and midgut (20-30min) as confirmed by Western blot, ELISA, and Immunofluorescence. The absorption of Scy-hepc affected the swimming, swarming and surfing motility of Vibrio harveyi and Bacillus thuringiensis isolated from E. akaara's gut. Moreover, Scy-hepc induced the downregulation of 40 assembly genes and the upregulation expression of 5, with the most significant divergence in gene expression between opportunistic pathogens and probiotics concentrated in their motility genes (PomA/B, MotA/B). In summary, this study shows that feeding AMP Scy-hepc can promote growth and bolster immunity in E. akaara. These beneficial effects are likely due to the absorption of Scy-hepc in the fish's foregut and midgut, which modulates the colonization and motility of commensal bacteria, leading to favorable changes in the composition of the foregut and midgut microbiota. Therefore, a profound understanding of the mechanisms by which antimicrobial peptides affect host gut microbiota will contribute to a comprehensive assessment of their advantages and potential application prospects as substitutes for antibiotics in fish health and improving aquaculture practices.

Contribution of gut microbiota to hepatic steatosis following F-53B exposure from the perspective of glucose and fatty acid metabolism

Altered gut microbiota is a pathogenic mechanism of 6:2 Cl-PFESA (F-53B)-induced hepatic steatosis, indicated by correlations between gut microbiota and lipid indices. However, the detailed mechanism remains unknown. In this study, adult zebrafish were exposed to 0.25, 5 and 100μg/L F-53B for 28 days to explore how microbiota regulate hepatic lipid metabolism from the perspective of glucose and fatty acid metabolism. Results showed glucose and fatty acids were transported from blood into liver after 100μg/L F-53B exposure, in which glucose was further transformed into acetyl-CoA and fatty acid. The accumulated fatty acids were then converted into triglycerides (TGs), inducing hepatic steatosis. Changes in the abundances of certain gut microbiota contributed to the above processes, which was verified by the fact that the levels of g_Crenobacter, g_Shewanella, and g_Vibrio restored to control levels after Lactobacillus rhamnosus GG intervention, and the levels of their related lipid indicators recovered partially towards the control levels. 0.25 and 5μg/L F-53B had no effect on the hepatic lipid profile due to the few changed TG synthesis related indicators. Our findings provide novel insights into lipid metabolic disorders caused by F-53B exposure, highlighting the health risks linked to gut microbial dysbiosis.

Butyrate-producing bacteria as probiotic supplement: beneficial effects on metabolism and modulation of behaviour in an obesity mouse model.

Obesity is a risk factor for cardio-metabolic and neurological disease. The contribution of gut microbiota to derangements of the gut-brain axis in the context of obesity has been acknowledged, particularly through physiology modulation by short-chain fatty acids (SCFAs). Thus, probiotic interventions and administration of SCFAs have been employed with the purpose of alleviating symptoms in both metabolic and neurological disease. We investigated the effects of four butyrate-producing bacteria from the Lachnospiraceae family on the development of metabolic syndrome and behavioural alterations in a mouse model of diet-induced obesity. Male mice were fed either a high-fat diet (HFD) or an ingredient-matched control diet for 2 months, and bacteria cultures or culture medium were given by gavage to HFD-fed mice every second day. Mice were assessed through a battery of metabolic and behaviour tests, and fluxes through the gut barrier and blood-brain barrier were determined using Dextran-based tracers. One of the administered bacteria from the Coprococcus genus, which produces butyrate and formate, afforded some degree of protection against the development of obesity and its complications. Results from this study, however, are insufficient to support brain health benefits of the bacteria tested. None of the bacteria modulated permeability through the gut or blood-brain barriers. Our results suggest health benefits of a bacteria from Lachnospiraceae family, and encourage further exploration of its use as probiotic.

Potential contribution of gut microbiota in the development of autoantibodies in T1D children carrying HLA-DRB1/DQB1 risk alleles: an experimental and in silico analysis.

This study aimed to investigate the prevalence of insulin autoantibody (IAA), glutamic acid decarboxylase antibody (GADA), and insulinoma-associated antigen-2 antibody (IA-2A) in type 1 diabetes (T1D) children based on the presence of predisposing HLA-II alleles. Additionally, to assess the sequence homology between autoantigens of islet cells and selected proteins derived from gut bacteria in terms of their binding capacities to HLA risk alleles, HLA-DRB1/DQB1 alleles were determined by PCR-SSOP in 111 T1D children (probands) along with 222 parents and 133 siblings. Autoantibodies were measured by ELISA, and in silico analysis was run as follows: protein extraction, homology and epitope prediction, peptide alignment, and HLA-peptide docking. Higher significant frequencies of DRB1*03:01, DQB1*02:01, and DQB1*03:02 alleles and DRB1*03:01 ~ DQB1*02:01 haplotype and lower frequencies of DRB1*11:01, DRB1*14:01, and DQB1*03:01 alleles were found in probands compared to parents and siblings. DRB1*11:01 ~ DQB1*03:01, DRB1*14:01 ~ DQB1*05:03, and DRB1*15:01-DQB1*06:02 haplotypes were significantly less frequent in the probands compared to parents. Out of 111 probands, 21 were seronegative, 90 tested positive for one autoantibody, and 15 showed the concurrent presence of three autoantibodies. Logistic regression analysis revealed that DRB1*04 ~ DQB1*03:02 haplotype was associated with the induction of GADA and IA-2A, while DRB1*11:01 ~ DQB1*03:01 was associated with seronegativity. Epitopes derived from GAD and gut bacteria showed strong binding capacities to HLA risk alleles. Due to the sequence similarities between gut bacteria-derived proteins and islet cell autoantigens and their potential for binding to HLA risk alleles, dysbiosis of gut microbiota can be considered another risk factor for the development of T1D, especially in genetically susceptible individuals.

Probiotics-role in alleviating the impact of alcohol liver disease and alcohol deaddiction: a systematic review.

There are few efficient treatment options for alcohol addiction, which continues to be a serious public health concern. The possible contribution of gut microbiota to the onset and progression of alcohol addiction has been brought to light by recent studies. Probiotics have become a cutting-edge intervention in the treatment of alcohol consumption disorder because of its favorable effects on gut health. The purpose of this systematic review is to assess the body of research on the advantages of probiotics in treating alcoholism and associated neuroinflammatory conditions. To find pertinent research published from January 2012 to 2023, a thorough search of electronic databases, including PubMed, Scopus, Google Scholar and Web of Science, was carried out. Included were studies looking at how probiotics affect neuroinflammation, gut- brain axis regulation, alcohol addiction, and related behaviors. Several investigations have shown how beneficial probiotics are in reducing systemic inflammation and alcoholic liver disease (ALD). Probiotic treatments successfully corrected the imbalance of microbiota, decreased intestinal permeability, and stopped the passage of bacterial constituents such lipopolysaccharides (LPS) into the bloodstream. Additionally, probiotics helped to regulate neurotransmitter pathways, especially those connected to GABA, glutamate, and dopamine, which are intimately linked to behaviors related to addiction. Furthermore, it was shown that probiotics altered the expression of neurotransmitter signaling and dopamine receptors. There is strong evidence from this systematic study that probiotics have potential advantages in treating alcohol addiction. The potential of probiotic therapies is demonstrated by the way they modulate important neurotransmitter pathways implicated in addiction, decrease neuroinflammation, and restore the balance of gut flora. To fully investigate the therapeutic potential of probiotics in treating alcohol addiction and enhancing the general wellbeing of those afflicted by this condition, more research is necessary.

Contribution of gut microbiota to biodegradation of polystyrene in Tenebrio molitor larvae: Microbiome under antibiotic suppression of Gram-positive, Gram-negative, and fungal microbes

The discovery of plastic biodegradation by insects such as Tenebrio molitor larvae has been well known, however, understanding of the roles of larval gut microorganisms is still very limited. The contribution of the gut microbes belonging to respective Gram-positive (G+), Gram-negative (G−), and fungal (F) groups remains unclear. In this study, we tested polystyrene (PS) biodegradation by T. molitor larvae under three selective antibiotics i.e., gentamicin sulfate (GMS) against G− bacteria, ampicillin (AMP) against G+ bacteria and nystatin (NS) against fungi. The larvae consumed and biodegraded PS foams with Mn 86.381 kDa and Mw 181.176 kDa under antibiotic suppressions at reduced rates versus control (CK) with a sequence of CK>GMS>AMP>NS group. Specifically, only NS group showed a significant decreased in consumption compared to the control. The gut microbial counts decreased with GMS, AMP, or NS addition during the PS feeding. The respective gut microbial counts decreased by 103 to 104 with GMS, AMP, or NS addition PS feeding. Analyses of DSC, TGA, FTIR confirmed oxidation and biodegradation in the presence of antibiotics. The ingested PS polymers were depolymerized and mass reduction with negative influence in the order of NS<AMP<GMS. The negative impact of antibiotic suppression on PS biodegradation process was as follows: anti-fungi reagent > anti-G+ bacteria > anti- G− bacteria. Changes in chemical functional groups are probably related to certain gut microbes, such as the fungal genus of Candida, and bacterial genera of unclassified Enterobacteriaceae and Lactobacillus. Our findings provided new insights into the mechanisms of the biodegradation of plastics in insects.

Molecular Insights: The Gut Microbiota's Impact on Colorectal Cancer

Globally, colorectal cancer (CRC) ranks second in terms of cancer-related fatalities. Several lines of evidence point to the gut microbiota's role in increasing inflammation and tumour growth, despite the fact that CRC is believed to be the result of a genetic-environmental interaction. A person's gut microbiota is made up of around 40 trillion bacteria. Next-generation sequencing technologies and metagenomics have advanced the understanding of the ecology of gut microbes and have contributed to the connection between gut microbiota and colorectal cancer. Numerous investigations conducted on both human and animal models have highlighted the part that specific gut bacterialike Fusobacterium nucleatum, Bacteroides fragilis with enterotoxigenic properties, and Escherichia coli play critical role in the development and progression of colorectal cancer (CRC). New directions for the use of gut microbiota in CRC diagnosis, prevention, and therapy have been made possible by metagenomic research. The contribution of gut microbiota to colorectal cancer development and its possible therapeutic uses are outlined in this review paper

Investigating the response of the butyrate production potential to major fibers in dietary intervention studies

Interventions involving dietary fibers are known to benefit host health. A leading contribution of gut microbiota is commonly recognized with production of short chain fatty acids (SCFA) suspected to play a key role. However, the detailed mechanisms are largely unknown, and apart from a well-described bifidogenic effect of some fibers, results for other bacterial taxa are often incongruent between studies. We performed pooled analyses of 16S rRNA gene data derived from intervention studies (n = 14) based on three fibers, namely, inulin-type fructans (ITF), resistant starch (RS), and arabinoxylan-oligosaccharides (AXOS), harmonizing the bioinformatics workflow to reveal taxa stimulated by those substrates, specifically focusing on the SCFA-production potential. The results showed an increased butyrate production potential after ITF (p < 0.05) and RS (p < 0.1) treatment via an increase in bacteria exhibiting the enzyme butyryl-CoA:acetate CoA-transferase (but) that was governed by Faecalibacterium, Anaerostipes (ITF) and Agathobacter (RS) respectively. AXOS did not promote an increase in butyrate producers, nor were pathways linked to propionate production stimulated by any intervention. A bifidogenic effect was observed for AXOS and ITF, which was only partly associated with the behavior of but-containing bacteria and largely represented a separate response. Low and high Ruminococcus abundances pre-intervention for ITF and RS, respectively, promoted an increase in but-containing taxa (p < 0.05) upon interventions, whereas initial Prevotella abundance was negatively associated with responses of butyrate producers for both fibers. Collectively, our data demonstrate targeted stimulation of specific taxa by individual fibers increasing the potential to synthesize butyrate, where gut microbiota composition pre-intervention strongly controlled outcomes.

A decade of insight: bibliometric analysis of gut microbiota's role in osteoporosis (2014-2024).

Osteoporosis represents a profound challenge to public health, underscoring the critical need to dissect its complex etiology and identify viable targets for intervention. Within this context, the gut microbiota has emerged as a focal point of research due to its profound influence on bone metabolism. Despite this growing interest, the literature has yet to see a bibliometric study addressing the gut microbiota's contribution to both the development and management of osteoporosis. This study aims to fill this gap through an exhaustive bibliometric analysis. Our objective is to uncover current research hotspots, delineate key themes, and identify future research trends. In doing so, we hope to provide direction for future studies and the development of innovative treatment methods. Relevant publications in this field were retrieved from the Web of Science Core Collection database. We used VOSviewer, CiteSpace, an online analysis platform and the R package "Bibliometrix" for bibliometric analysis. A total of 529 publications (including 351 articles and 178 reviews) from 61 countries, 881 institutions, were included in this study. China leads in publication volume and boast the highest cumulative citation. Shanghai Jiao Tong University and Southern Medical University are the leading research institutions in this field. Nutrients contributed the largest number of articles, and J Bone Miner Res is the most co-cited journal. Of the 3,166 scholars who participated in the study, Ohlsson C had the largest number of articles. Li YJ is the most co-cited author. "Probiotics" and "inflammation" are the keywords in the research. This is the first bibliometric analysis of gut microbiota in osteoporosis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We investigate the impact of gut microbiome dysregulation and its associated inflammation on OP progression, a topic that has garnered international research interest in recent years. Additionally, our study delves into the potential of fecal microbiota transplantation or specific dietary interventions as promising avenues for future research, which can provide reference for the researchers who focus on this research filed.

A Well-Established Gut Microbiota Enhances the Efficiency of Nutrient Metabolism and Improves the Growth Performance of Trachinotus ovatus

The gut microbiota has become an essential component of the host organism and plays a crucial role in the host immune system, metabolism, and physiology. Nevertheless, our comprehension of how the fish gut microbiota contributes to enhancing nutrient utilization in the diet and improving host growth performance remains unclear. In this study, we employed a comprehensive analysis of the microbiome, metabolome, and transcriptome to analyze intestines of the normal control group and the antibiotic-treated model group of T. ovatus to investigate how the gut microbiota enhances fish growth performance and uncover the underlying mechanisms. First, we found that the growth performance of the control group was significantly higher than that of the antibiotic-treated model under the same feeding conditions. Subsequent multiomics analyses showed that the gut microbiota can improve its own composition by mediating the colonization of some probiotics represented by Lactobacillus in the intestine, improving host metabolic efficiency with proteins and lipids, and also influencing the expression of genes in signaling pathways related to cell proliferation, which together contribute to the improved growth performance of T. ovatus. Our results demonstrated the important contribution of gut microbiota and its underlying molecular mechanisms on the growth performance of T. ovatus.

Characterizations of gut bacteriome, mycobiome, and virome of healthy individuals living in sea-level and high-altitude areas.

The contribution of gut microbiota to human high-altitude adaptation remains inadequatelyunderstood. Here a comparative analysis of gut microbiota was conducted between healthy individuals living at sealevel and high altitude using deep whole-metagenome shotgun sequencing, to investigate the adaptivemechanisms of gut microbiota in plateau inhabitants. The results showed the gut bacteriomes in high-altitude individuals exhibited greater within-samplediversity and significant alterations in both bacterial compositional and functional profiles when compared to thoseof sea-level individuals, indicating the potential selection of unique bacteria associated with high-altitudeenvironments. The strain-level investigation revealed enrichment of Collinsella aerofaciens and Akkermansiamuciniphila in high-altitude populations. The characteristics of gut virome and gut mycobiome were alsoinvestigated. Compared to sea-level subjects, high-altitude subjects exhibited a greater diversity in their gut virome,with an increased number of viral operational taxonomic units (vOTUs) and unique annotated genes. Finally,correlation analyses revealed 819 significant correlations between 42 bacterial species and 375 vOTUs, while nosignificant correlations were observed between bacteria and fungi or between fungi and viruses. The findings have significantly contributed to an enhanced comprehension of the mechanismsunderlying the high-altitude geographic adaptation of the human gut microbiota.

Dynamic changes of gut microbiota composition during the intervention of apple polyphenols extract to alleviate high-carbohydrate-diet induced body weight gain

To explore the contribution of gut microbiota to the ameliorative effects of apple polyphenols extract (APE) on body weight (BW) gain induced by high-carbohydrate-diet, C57BL/6 male mice were fed with standard diet (CON), conventional high carbohydrates diet (HCD) and high simple carbohydrates diet (HSCD) with or without APE intervention for 12 consecutive weeks. The composition and differences of microbiota at 6th and 12th weeks were analyzed using LEfSe and STAMP. Significantly increased BW accompanied by obviously increased Firmicutes/Bacteroidetes ratio and Dubosiella abundance, decreased abundances of Verrucomicrobia, Proteobacteria, Akkermansia and Parabacteroides were observed in HCD and HSCD groups compared to the CON group 12 weeks later. Additionally, the BW gain in HSCD was different from that in HCD, which was lower within the first 6 weeks than HCD, then was reversed during the next 6 weeks and led to relatively higher final BW. However, APE intervention, especially the high dose, reduced the BW and restored microbiota disorder, especially obviously decreased Firmicutes/Bacteroidetes ratio and the abundance of Dubosiella, and increased abundances of Verrucomicrobia and Akkermansia, which also displayed significant difference to the data at 6th week after APE intervention, this partly explained the ameliorated effects of APE on BW control presently. Furthermore, Akkermansia might be the primary target genus for APE intervention to regulate gut microbiota and affect BW. Thus, our study supported the more adverse effects of HSCD on BW than HCD, and APE might be a promising nutraceutical for BW control by restoring microbiota compositions and enriching Akkermansia.

Multiomics Analysis Reveals Leucine Deprivation Promotes Bile Acid Synthesis by Upregulating Hepatic CYP7A1 and Intestinal Turicibacter sanguinis in Mice

BackgroundLeucine, a branched-chain amino acid, participates in the regulation of lipid metabolism and the composition of the intestinal microbiota. However, the related mechanism remains unclear. ObjectivesHere, we aimed to reveal the potential mechanisms by which hepatic CYP7A1 (a rate-limiting enzyme for bile acid [BA] synthesis) and gut microbiota coregulate BA synthesis under leucine deprivation. MethodsTo this end, 8-wk-old C57BL/6J mice were fed with either regular diets or leucine-free diets for 1 wk. Then, we investigated whether secondary BAs were synthesized by Turicibacter sanguinis in 7-wk-old C57BL/6J germ-free mice gavaged with T. sanguinis for 2 wk by determining BA concentrations in the plasma, liver, and cecum contents using liquid chromatography-tandem mass spectrometry. ResultsThe results showed that leucine deprivation resulted in a significant increase in total BA concentration in the plasma and an increase in the liver, but no difference in total BA was observed in the cecum contents before and after leucine deprivation. Furthermore, leucine deprivation significantly altered BA profiles such as taurocholic acid and ω-muricholic acid in the plasma, liver, and cecum contents. CYP7A1 expression was significantly upregulated in the liver under leucine deprivation. Leucine deprivation also regulated the composition of the gut microbiota; specifically, it significantly upregulated the relative abundance of T. sanguinis, thus enhancing the conversion of primary BAs into secondary BAs by intestinal T. sanguinis in mice. ConclusionsOverall, leucine deprivation regulated BA profiles in enterohepatic circulation by upregulating hepatic CYP7A1 expression and increasing intestinal T. sanguinis abundance. Our findings reveal the contribution of gut microbiota to BA metabolism under dietary leucine deprivation.

The Role of Gut-derived Short-Chain Fatty Acids in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic condition affecting the central nervous system (CNS), where the interplay of genetic and environmental factors influences its pathophysiology, triggering immune responses and instigating inflammation. Contemporary research has been notably dedicated to investigating the contributions of gut microbiota and their metabolites in modulating inflammatory reactions within the CNS. Recent recognition of the gut microbiome and dietary patterns as environmental elements impacting MS development emphasizes the potential influence of small, ubiquitous molecules from microbiota, such as short-chain fatty acids (SCFAs). These molecules may serve as vital molecular signals or metabolic substances regulating host cellular metabolism in the intricate interplay between microbiota and the host. A current emphasis lies on optimizing the health-promoting attributes of colonic bacteria to mitigate urinary tract issues through dietary management. This review aims to spotlight recent investigations on the impact of SCFAs on immune cells pivotal in MS, the involvement of gut microbiota and SCFAs in MS development, and the considerable influence of probiotics on gastrointestinal disruptions in MS. Comprehending the gut-CNS connection holds promise for the development of innovative therapeutic approaches, particularly probiotic-based supplements, for managing MS.

Exploration of gut microbiome and inflammation: A review on key signalling pathways

The gut microbiome, a crucial component of the human system, is a diverse collection of microbes that belong to the gut of human beings as well as other animals. These microbial communities continue to coexist harmoniously with their host organisms and perform various functions that affect the host's general health. Each person's gut microbiota has a unique makeup. The gut microbiota is well acknowledged to have a part in the local as well as systemic inflammation that underlies a number of inflammatory disorders (e.g., atherosclerosis, diabetes mellitus, obesity, and inflammatory bowel disease).The gut microbiota's metabolic products, such as short-chain fatty acids (butyrate, propionate, and acetate) inhibit inflammation by preventing immune system cells like macrophages and neutrophils from producing pro-inflammatory factors, which are triggered by the structural elements of bacteria (like lipopolysaccharide). The review's primary goal is to provide comprehensive and compiled data regarding the contribution of gut microbiota to inflammation and the associated signalling pathways.

Altered gut microbiota in Taiwanese A97S predominant transthyretin amyloidosis with polyneuropathy

Increasing evidence suggests that gut microbiota alterations are related to development and phenotypes of many neuropsychiatric diseases. Here, we evaluated the fecal microbiota and its clinical correlates in patients with hereditary transthyretin amyloidosis (ATTRv) and polyneuropathy. Fecal microbiota from 38 ATTRv patients and 39 age-matched controls was analyzed by sequencing 16S V3–V4 ribosomal RNA, and its relationships with clinical characteristics of polyneuropathy and cardiomyopathy were explored. The familial amyloidotic polyneuropathy stage was stage I, II, and III in 13, 18, and 7 patients. 99mTc-PYP SPECT showed a visual score of 2 in 15 and 3 in 21 patients. The gut microbiota of ATTRv patients showed higher alpha diversity (ASV richness and Shannon effective numbers) and dissimilar beta diversity compared to controls. Relative abundance of microbiota was dominated by Firmicutes and decreased in Bacteroidetes in ATTRv patients than in controls. Patients with more myocardial amyloid deposition were associated with increased alpha diversity, and the abundance of Clostridia was significantly correlated with pathophysiology of polyneuropathy in ATTRv patients. These findings demonstrated alterations in the gut microbiota, especially Firmicutes, in ATTRv. The association between altered microbiota and phenotypes of cardiomyopathy and polyneuropathy might suggest potential contributions of gut microbiota to ATTRv pathogenesis.

Gut microbiota regulates host melatonin production through epithelial cell MyD88

ABSTRACT Melatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.

Ginsenosides retard atherogenesis via remodelling host-microbiome metabolic homeostasis.

Panax ginseng is widely applied in the adjuvant treatment of cardiometabolic diseases in clinical practice without clear mechanisms. This study aims to clearly define the efficacy and underlying mechanism of P.ginseng and its active components in protecting against atherosclerosis. The anti-atherogenic efficacy of total ginseng saponin extract (TGS) and its components was evaluated on Ldlr-/- mice. Gut microbial structure was analysed by 16S rRNA sequencing and PCR. Bile acid profiles were revealed using targeted metabolomics with LC-MS/MS analysis. The contribution of gut microbiota to atherosclerosis was assessed by co-housing experiments. Ginsenoside Rb1, representing protopanaxadiol (PPD)-type saponins, increased intestinal Lactobacillus abundance, resulting in enhanced bile salt hydrolase (BSH) activity to promote intestinal conjugated bile acid hydrolysis and excretion, followed by suppression of enterohepatic farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signal, and thereby increased cholesterol 7α-hydroxylase (CYP7A1) transcriptional expression and facilitated metabolic elimination of cholesterol. Synergistically, protopanaxatriol (PPT)-type saponins, represented by ginsenoside Rg1, protected against atherogenesis-triggered gut leak and metabolic endotoxaemia. Ginsenoside Rg1 directly induced mucin production to nutritionally maintain Akkermansia muciniphila, which reciprocally inhibited gut permeation. Rb1/Rg1 combination, rather than a single compound, can largely mimic the holistic efficacy of TGS in protecting Ldlr-/- mice from atherogenesis. Our study provides strong evidence supporting TGS and ginsenoside Rb1/Rg1 combinations as effective therapies against atherogenesis, via targeting different signal nodes by different components and may provide some elucidation of the holistic mode of herbal medicines.

Human microbiota from drug-naive patients with obsessive-compulsive disorder drives behavioral symptoms and neuroinflammation via succinic acid in mice.

Emerging evidence suggests that the gut microbiota is closely related to psychiatric disorders. However, little is known about the role of the gut microbiota in the development of obsessive-compulsive disorder (OCD). Here, to investigate the contribution of gut microbiota to the pathogenesis of OCD, we transplanted fecal microbiota from first-episode, drug-naive OCD patients or demographically matched healthy individuals into antibiotic-treated specific pathogen-free (SPF) mice and showed that colonization with OCD microbiota is sufficient to induce core behavioral deficits, including abnormal anxiety-like and compulsive-like behaviors. The fecal microbiota was analyzed using 16 S rRNA full-length sequencing, and the results demonstrated a clear separation of the fecal microbiota of mice colonized with OCD and control microbiota. Notably, microbiota from OCD-colonized mice resulted in injured neuronal morphology and function in the mPFC, with inflammation in the mPFC and colon. Unbiased metabolomic analyses of the serum and mPFC region revealed the accumulation of succinic acid (SA) in OCD-colonized mice. SA impeded neuronal activity and induced an inflammatory response in both the colon and mPFC, impacting intestinal permeability and brain function, which act as vital signal mediators in gut microbiota-brain-immune crosstalk. Manipulations of dimethyl malonate (DM) have been reported to exert neuroprotective effects by suppressing the oxidation of accumulated succinic acid, attenuating the downstream inflammatory response and neuronal damage, and can help to partly improve abnormal behavior and reduce neuroinflammation and intestinal inflammation in OCD-colonized mice. We propose that the gut microbiota likely regulates brain function and behaviors in mice via succinic acid signaling, which contributes to the pathophysiology of OCD through gut-brain crosstalk and may provide new insights into the treatment of this disorder.

Gut microbiota and polycystic ovary syndrome, focus on genetic associations: a bidirectional Mendelian randomization study.

The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota. We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry. IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS. Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship. This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.