Gut Microbial Profiles Research Articles

P1318 Temporal Changes of Gut Microbiota and Micro-RNAs according to Disease Activity in Chronic Colitis

Abstract Background Both gut microbiota and micro-RNAs (miRNAs) have been implicated in the pathogenesis of inflammatory bowel disease. We aimed to investigate the temporal changes and their interactions between gut microbiota and miRNAs according to the disease activity using multi-omics analysis in a murine chronic colitis model. Methods Chronic colitis was induced in the C57BL/6 mice by three rounds of 2.5% DSS exposure. Mice were divided into three groups (n= 8 per group): control group, active group (sacrified at 3 days after the third DSS), and recovery group (sacrificed at 80 days after the third DSS). Clinical activities including weight change and histologic findings of colonic segments were examined. DNA was extracted from mouse feces, and 16S rRNA gene sequencing was performed to evaluate changes in gut microbiota. miRNA expression levels were measured by microarray analysis from mouse colonic tissues. Correlation and network analyses were performed to evaluate the interactions between gut microbiota and miRNAs. Results Alpha diversity indices were increased in the active group compared to control and recovery group. PCoA of metagenomic sequencing showed that the gut microbial profile of the active group was distinctly different from the control group, while the gut microbial profile of the recovery group was similar to the control group. On the other hand, PCoA of miRNA microarray showed that the active group had a significantly different miRNA expression pattern compared to the control group, while the recovery group had a similar miRNA expression pattern to the active group. In taxonomic and miRNA analyses, 147 differential abundant bacterial ASVs and 30 differential expressed miRNAs were identified in the active group compared to the recovery group. Spearman correlation and network analysis between gut microbiota and miRNAs, which showed significant differences between the active and the recovery groups, revealed significant associations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p. Conclusion In the active phase of chronic colitis, the gut microbial composition and miRNA expression were significantly altered, while in the recovery phase of chronic colitis, the gut microbial profile was similar to that of control, but a significantly different miRNA expression pattern was observed. Specific miRNAs were associated with specific bacterial ASVs, suggesting the interactions between miRNAs and gut microbiota in the development of chronic colitis. Our data suggested significant correlations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p in the active phase of chronic colitis.

Periodontitis Exacerbates Colorectal Cancer by Altering Gut Microbiota-Derived Metabolomics in Mice.

The correlation between periodontitis and colorectal cancer (CRC) has drawn widespread attention. However, how periodontitis affects CRC progression remains unclear. C57BL/6 mice were used to establish experimental periodontitis and CRC model. Histological alterations of periodontium and colon were observed by hematoxylin and eosin staining. Micro-computed tomography (micro-CT) was applied to evaluate alveolar bone loss (ABL). Tumor growth was detected by immunofluorescence. Gut bacteria were analyzed using 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was performed to observe the alterations of gut microbial metabolites. The detection of associated pathways was carried out using quantitative real-time PCR (qRT-PCR). Experimental periodontitis significantly induced increases in tumor number in mice with CRC. Double immunofluorescence for Ki67 and β-catenin, as well as Cyclin D1 and β-catenin, indicated that experimental periodontitis observably promoted tumor growth. 16S rRNA sequencing and untargeted metabolomics analysis displayed that experimental periodontitis altered gut microbial community and metabolite profiles in CRC mice. Notably, we found that experimental periodontitis dramatically increased the level of three oncometabolites (serotonin, adenosine, and spermine) in mice with CRC. Alterations of gut microbial community and metabolites might be relevant in experimental periodontitis deteriorating CRC.

P1327 Microbial signatures associated with Inflammatory Bowel Disease in Australia: baseline data from the Australian IBD Microbiome study

Abstract Background Microbial dysbiosis is associated with Crohn’s disease (CD) and ulcerative colitis (UC) onset and disease activity, however, large-scale data pertaining to Australian patients are limited1. This study aimed to describe the differences in gut microbiota composition between patients with IBD and healthy controls within the Australian IBD Microbiome (AIM) study2. Methods Paired faecal and oral samples alongside participant demographics and disease characteristics were collected at baseline from all healthy controls (HC) and IBD patients enrolled in the Australian IBD Microbiome (AIM) study from June 2019 to November 2023. Faecal and oral samples were self-collected in DNA stabilising buffer, aliquoted and stored at -80oC until extraction. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Chao1) between groups were assessed using Mann-Whitney U tests. Beta diversity (weighted UniFrac dissimilarity) in bacterial communities were shown using Principal Coordinate Analysis (PCoA), and significance of variance was tested using ADONIS in R. Results 751 participants (305 HC, 232 CD, 214 UC) returned baseline faecal (n = 697) and/or oral samples (n = 737) and were included in the analysis, with patient group characteristics presented in Table 1. Most IBD patients were in clinical remission (Table 1). However, CD and UC patients had comparably lower faecal alpha diversity than the HC group (Figure 1A). Faecal beta diversity differed between CD, UC, and HC groups (Figure 1B). Five phyla were significantly different between the three groups in faecal samples (Figure 1C). No significant inter-group differences were seen with oral microbial analysis. Conclusion Compared to healthy adults, patients with IBD in Australia have distinct gut microbial profiles. Faecal rather than oral microbial sampling demonstrated a difference in community structure between IBD and healthy groups. Incorporating longitudinal microbial sampling and increasing sequencing resolution may elucidate a pathogenic relationship between gut microbiota and IBD.

P0203 Unique faecal & oral microbiota signatures in first degree relatives of inflammatory bowel disease patients

Abstract Background While the aetiology of IBD is unknown, a range of genetic and environmental risk factors have been described. First-degree relatives (FDRs; siblings, parents and children) of IBD patients share many of these factors. To better understand the interplay between environmental and genetic risk factors, we evaluated the gut microbial profiles of an FDR cohort, their IBD probands and healthy controls (HC). The aim was to identify whether FDRs of IBD patients have healthy or IBD-like microbial features. Methods All participants were recruited as part of the Australian IBD Microbiome (AIM) study. Participants were selected based on self-reported first-degree relative status (n=68) and, where possible, affected IBD relatives (n=24) were included for comparison. All participants were antibiotic free for 3-months prior to baseline sampling. Oral and faecal samples underwent 16S rRNA sequencing. The Microbiome Research Centre 16S analysis pipeline and R studio were used for statistical analysis and data visualisation. Results The FDR group was predominantly female (63%) with a mean age of 49.7 years and BMI of 25.5 kg/m2. The IBD cohort was significantly different in age to FDR (mean 36.7; p < 0.05) but not controls (mean 40.4 years) and BMI was comparable between groups. European Australians were the most represented ethnic group (47.6%) and 98.6% of participants were non-smokers. Oral microbiota profiles showed no significant difference in alpha diversity across FDR, IBD and HC groups. Differential abundance analysis of the oral microbiota revealed FDRs had increased abundance of Oribacterium, Granulicatella, Lachnoanaerobaculum and Rothia compared to HC, and increased levels of Capnocytophaga, Tannerella and Abiotrophia compared to the IBD group. In agreement with other studies, faecal microbial profiles in the IBD group had significantly reduced alpha diversity compared to both FDR and HC groups. All groups were compositionally different by Bray-Curtis beta dissimilarity analysis (p<0.018). FDRs had higher abundance of Akkermansia, Alistipes and Monoglobus compared to IBD and HC groups. FDRs and IBD shared similar abundance of Butyricicoccus which was lower than the HCs. Conclusion FDR oral microbiome signatures had greater variance from HC than IBD groups. Faecal microbial analysis showed distinct differences with enrichment of key beneficial genera in the FDR group. FDR profiles however still shared significant gut microbial features with the IBD group, remaining distinct from healthy controls. FDRs oral microbiome was higher in opportunistic pathogens and IBD-like whereas faecal composition was protective, rich in beneficial metabolite producing genera.

Potential roles of cigarette smoking on gut microbiota profile among Chinese men

BackgroundCigarette smoking is posited as a potential factor in disrupting the balance of the human gut microbiota. However, existing studies with limited sample size have yielded inconclusive results.MethodsHere, we assessed the association between cigarette smoking and gut microbial profile among Chinese males from four independent studies (N total = 3308). Both 16S rRNA and shotgun metagenomic sequencing methods were employed, covering 206 genera and 237 species. Microbial diversity and abundance were compared among non-smokers, current smokers, and former smokers.ResultsActinomyces[g], Atopobium[g], Haemophilus[g], Turicibacter[g], and Lachnospira[g] were found to be associated with smoking status (current smokers vs. non-smokers). Metagenomic data provided a higher resolution at the species level, particularly for the Actinomyces[g] branch. Additionally, serum γ-glutamylcysteine (γ-Glu-Cys) was found to have a potential role in connecting smoking and Actinomyces[g]. Furthermore, we revealed putative mediation roles of the gut microbiome in the associations between smoking and common diseases including cholecystitis and type 2 diabetes.ConclusionsWe characterized the gut microbiota profile in male smokers and further revealed their potential involvement in mediating the impact of smoking on health outcomes. These findings advance our understanding of the intricate association between cigarette smoking and the gut microbiome.

Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis

BackgroundThe spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world’s population, with a significant risk of hepatic and cardiometabolic complications. Different stages of...

2'-Fucosyllactose attenuates aging-related metabolic disorders through modulating gut microbiome-T cell axis.

Aging-related metabolic disorders seriously affect the lifespan of middle-aged and older people, potentially due to disruptions in the adaptive immune and gut microbial profiles. Dietary intervention offers a promising strategy for maintaining metabolic health. This study aimed to investigate the ameliorative effect of 2'-fucosyllactose (2'-FL) on aging-induced metabolic dysfunction and the underlying mechanisms. The results revealed that 2'-FL significantly relieved aging-related metabolic disorders, including weight gain, lipid deposition, dyslipidemia, glucose intolerance, systemic inflammation, and abnormal hepatic metabolism. Flow cytometry analysis revealed a significant reduction in T cytotoxic (Tc), T helper (Th), and regulatory T (Treg) cells and a significant increase in Th17 cells in aged mice, while 2'-FL relieved the aging-induced proportional changes in Th and Th17 subtypes. The aging intestinal microecology was characterized by higher Th17/Treg ratios, impaired gut barrier function, lower gut bacterial diversity, decreased abundance of beneficial genera including Ligilactobacillus, Colidextribacter, Mucispirillum, and Lachnoclostridium, and increased abundance of harmful bacteria including Turicibacter and Desulfovibrio, which was ameliorated by 2'-FL treatment. These findings highlight that 2'-FL is an ideal dietary prebiotic for improving aging-related metabolic disorders by modulating both the adaptive immune system and the gut microbial profile.

In vivo mechanism of the interaction between trimethylamine lyase expression and glycolytic pathways.

Recent studies confirmed that host-gut microbiota interactions modulate disease-linked metabolite TMA production via TMA lyase. However, microbial enzyme production mechanisms remain unclear. In the present study, we investigated the impact of dietary and intervention factors on gut microbiota, microbial gene expression, and the interplay between TMA lyase and glycolytic pathways in mice. Using 16S rRNA gene sequencing, metagenomics, and metabolomics, the gut microbiota composition and microbial functional gene expression profiles related to TMA lyase and glycolytic enzymes were determined. The results revealed that distinct diets and intervention factors altered gut microbiota, gene expression, and metabolites linked to glycine metabolism and glycolysis. Notably, an arabinoxylan-rich diet suppressed genes linked to choline, glycine, glycolysis, and TMA lyase, favoring glycine utilization via pyruvate pathways. Glycolytic inhibitors amplified these effects, mainly inhibiting pyruvate kinase. Our findings underscored the crosstalk between TMA lyase and glycolytic pathways, regulating glycine levels, and suggested avenues for targeted interventions and personalized diets to curb choline TMA lyase production.

The effect of probiotics, prebiotics and synbiotics on gut microbial community profile in overweight and obese Latin American and Caribbean populations: a systematic review of human trials

The effect of probiotics, prebiotics and synbiotics on gut microbial community profile in overweight and obese Latin American and Caribbean populations: a systematic review of human trials

MICROBIOME-KIDNEY METABOLISM PROVIDES INSIGHT INTO THE MECHANISM OF ICARIIN ALLEVIATES AGING IN OLDER FEMALE MICE

Abstract The average life expectancy of women in most countries and regions is significantly higher than men’s. Whether in rich developed countries or relatively poor third-world countries, women are more likely to live. Our previous study revealed that Icariin enhances youth-like features by attenuating the declined gut microbiota in older male mice. To further study the mechanism of icariin on delaying aging in older female mice on gut microbiota and metabolism, two age groups of C57BL/6J female mice (8 week- and 24 month- mice) were given a single dose of icariin at 100mg/kg by gavage for 15 days. The 16S rRNA gene pyrosequencing analyzed the fecal microbiome. We observed clear differences in gut microbial profiles between the young and older female mice. Interestingly, while older male mice did not show this effect, treatment with icariin increased the abundance of the short-chain fatty acid (SCFA)-producing bacteria Akkermansia muciniphila and Eubacterium ramulus in older female mice, bringing their levels close to those of untreated young female mice at the species level. Further, we used non-targeted metabolomics technology to detect all metabolites in the kidney. We found that the level of D-serine in the kidneys of older female mice was significantly lower than that of young female mice, and the metabolite levels were significantly increased after icariin treatment. SCFA and D-serine are gut microbial-derived products with kidney-protective properties. This study provides valuable insights into the molecular mechanisms of icariin, highlighting target characteristics and key pathways for slowing the aging process.

Gut Microbial Composition and Antibiotic Resistance Profiles in Dairy Calves with Diarrhea.

Calf diarrhea is a prevalent and significant health issue in dairy farming, severely impacting feed intake, weight gain, and survival rates in young calves. This study aimed to investigate the microbial composition and antibiotic resistance profiles of diarrheic calves to provide insights into the epidemiology and management of the condition. The prevalence of diarrhea in 1685 calves was analyzed. Rectal fecal samples were collected from five healthy and five diarrheic Holstein calves on a large dairy farm in Shaanxi Province, China. High-throughput 16S-rRNA sequencing and PCR were utilized for microbial and resistance gene analysis. In 2023, the overall diarrhea rate among 1685 calves was 9.08%, with a significantly higher diarrhea rate during the suckling period (8.13%) compared to the post-weaning period (0.95%) (p < 0.001). No differences in species diversity and richness were detected among the different groups. However, LEfSe analysis identified six genera (Eubacterium, Eubacteriaceae, Prevotella, Comamonadaceae, Comamonas, and Firmicutes) significantly enriched in diarrheic calves compared to healthy ones (LDA scores > 2, p < 0.05). Additionally, antibiotic resistance genes for quinolones, β-lactams, chloramphenicol, tetracyclines, and aminoglycosides were detected, with significantly higher prevalence in diarrheic calves. These findings demonstrate distinct microbial and antibiotic resistance profiles between healthy and diarrheic calves, emphasizing the importance of microbial management in controlling calf diarrhea.

Effects of a Paternal Diet High in Animal Protein (Casein) versus Plant Protein (Pea Protein with added Methionine) on Offspring Metabolic and Gut Microbiota Outcomes in Rats.

Evidence suggests that paternal diet can influence offspring metabolic health intergenerationally but whether dietary animal and plant proteins differ in their impact on fathers and their offspring is not known. Our objective was to examine the effects of a paternal diet high in casein versus pea protein on fathers and their offspring. Five-week-old male rats were fed: 1) control, 2) high animal protein (AP, 36.1% of energy as casein), or 3) high plant protein (PP, 36.1% of energy as pea protein with added methionine) diets for 8-11 weeks before being mated. Offspring were challenged with a high fat/sucrose diet (HFD) from 10-16 weeks of age. Metabolic and microbial outcomes were assessed in both generations. In fathers fed PP diet, enhanced insulin sensitivity and lower liver triglycerides were seen alongside altered hepatic microRNA expression and gut microbial profiles. Few changes were seen in their offspring. In contrast, the paternal AP diet influenced adult offspring hepatic microRNA expression and programmed a latent increase in adiposity, dysregulated satiety hormones, and modified gut microbial composition in their adult offspring that occurred following the HFD. Overall, a diet high in pea protein with added methionine demonstrated protective effects on biomarkers of metabolic health in the fathers but led to minimal effects on the offspring while a paternal diet high in casein led to evidence of an increase in characteristics of metabolic dysfunction in their adult offspring when unmasked by exposure to a HFD for 6 weeks.

Effects of Sophora flavescens dietary supplementation on the growth performance, haematological indices, and intestinal bacterial community of Oreochromis niloticus.

Sophora flavescens is considered to be of various medicinal and economic importance. Previous studies have shown that it has antibacterial, antioxidant, and immune-enhancing functions. To explore the full potential of S. flavescens in fish feed development, we investigated the effects of different levels of S. flavescens added to the diet on the growth performance, haematological indices, and the intestinal bacterial community of Nile tilapia (Oreochromis niloticus). The feeding trial lasted for 56 days, and the initial weight of the fish was 40.00 ± 5.00 g. Nile tilapia were randomly divided into six groups: a control group (CN) and five S. flavescens supplementation groups (0.02%, 0.04%, 0.08%, 0.16%, and 0.3% [w/w] of S. flavescens in diet). The growth performance of fish increased first and then decreased with the increase of S. flavescens supplemental level. Compared with other experimental groups, the growth performance of fish supplemented with 0.08% S. flavescens was significantly improved (p < 0.05). Haematological indices exhibited that erythrocyte (RBC), along with leucocyte (WBC) indices, exhibited a secondary trend of increasing and then decreasing with the increase of S. flavescens, reaching the highest level at 0.08% (p < 0.05). However, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC) exhibited a secondary trend of first decreasing and then increasing with the increase of S. flavescens and reached the lowest value at 0.08% (p < 0.05). Compared with the CN, alkaline phosphatase (AKP) significantly decreased and changed when the additional amount of S. flavescens was 0.04% in each treatment group (p < 0.05). In another way, the gut microbial profiles revealed that Bacteroides dominated the gut communities, and compared with the control group, two uncultured bacteria were suppressed. In addition, when the supplemental level of S. flavescens was more significant than 0.04%, the proliferation of Arcobacter cryaerophilus, Solibacillus silvestris, and Escherichia sp. in the gut of Nile tilapia was promoted. The results revealed that S. flavescens, as an additive to the Nile tilapia diet with levels ranging from 0.04% to 0.08%, can enhance the growth performance and immunity and promote the proliferation of intestinal beneficial bacteria of Nile tilapia.

Gut microbial and metabolomics profiles reveal the potential mechanism of fecal microbiota transplantation in modulating the progression of colitis-associated colorectal cancer in mice

PurposeIntestinal flora promotes the pathogenesis of colorectal cancer (CRC) through microorganisms and their metabolites. This study aimed to investigate the composition of intestinal flora in different stages of CRC progression and the effect of fecal microbiota transplantation (FMT) on CRC mice.MethodsThe fecal microbiome from healthy volunteers (HC), colorectal adenoma (CRA), inflammatory bowel disease (IBD), and CRC patients were analyzed by 16s rRNA gene sequencing. In an azoxymethane (AOM)/dextran-sulfate-sodium (DSS)-induced CRC mouse, the effect of FMT from HC, CRA, CRC, and IBD patients on CRC mice was assessed by histological analysis. Expression of inflammation- EMT-associated proteins and Wnt/β-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed.ResultPrevotella, Faecalibacterium, Phascolarctobacterium, Veillonella, Alistipes, Fusobacterium, Oscillibacter, Blautia, and Ruminococcus abundance was different among HC, IBD, CRC, and CRA patients. HC-FMT alleviated disease progression and inflammatory response in CRC mice, inhibited splenic T help (Th)1 and Th17 cell numbers, and suppressed the EMT and Wnt/β-catenin pathways in tumor tissues of CRC mice. IBD-FMT, CRA-FMT, and CRC-FMT played deleterious roles; the CRC-FMT mice exhibited the most malignant phenotype. Compared with the non-FMT CRC mice, Muribaculaceae abundance was lower after FMT, especially lowest in the IBD-FMT group; while Lactobacillus abundance was higher after FMT and especially high in HC-FMT. Akkermansia and Ileibacterium abundance increased after FMT-HC compared to other groups. Metabolite correlation analysis revealed that Muribaculaceae abundance was significantly correlated with metabolites such as Betaine, LysoPC, and Soyasaponin III. Lactobacillus abundance was positively correlated with Taurocholic acid 3-sulfate, and Ileibacterium abundance was positively correlated with Linoleoyl ethanolamide.ConclusionThe different intestinal microbiota communities of HC, IBD, CRA, and CRC patients may be attributed to the different modulation effects of FMT on CRC mice. CRC-FMT promoted, while HC-FMT inhibited the progress of CRC. Increased linoleoyl ethanolamide levels and abundance of Muribaculaceae, Akkermansia, and Ileibacterium and reduced Fusobacterium might participate in inhibiting CRC initiation and development. This study demonstrated that FMT intervention could restore the intestinal microbiota and metabolomics of CRC mice, suggesting FMT as a potential strategy for CRC therapy.

Effects of lambda-cyhalothrin on gut microbiota and related bile acid metabolism in mice

Since the gut microbiota plays a crucial role in host metabolism and homeostasis, its alterations induced by xenobiotics such as pesticides, could pose a risk to host health. The pyrethroid insecticides were frequently detected in surface water (up to 13 mg/L worldwide), sediments, and agricultural products; additionally, some previous studies indicated that pyrethroid insecticides could cause disruption of gut homeostasis. Hence herein, the normally used pyrethroid lambda-cyhalothrin (LCT) was selected and studied for its effects on the intestinal microbial community and its related bile acid metabolism using mice as the model species. Results showed that the total amount of bile acids in plasma and fecal samples from LCT treated mice markedly increased compared to controls, which could be mainly ascribed to the significantly raised proportions of taurine conjugated bile acids in plasma, and the increase in fecal secondary bile acids. In gut microbial profiles, a significantly increased richness of Prevotellacea and a depletion of Lachnospiraceae were found at the family level upon the treatment with lambda-cyhalothrin. In conclusion, results obtained on bacterial and bile acid profiles corroborate that the treatment of mice with LCT could affect gut microbial community with accompanying changes in bile acid homeostasis.

Chronic corticosterone exposure causes anxiety- and depression-related behaviors with altered gut microbial and brain metabolomic profiles in adult male C57BL/6J mice

Chronic exposure to glucocorticoids in response to long-term stress is thought to be a risk factor for major depression. Depression is associated with disturbances in the gut microbiota composition and peripheral and central energy metabolism. However, the relationship between chronic glucocorticoid exposure, the gut microbiota, and brain metabolism remains largely unknown. In this study, we first investigated the effects of chronic corticosterone exposure on various domains of behavior in adult male C57BL/6J mice treated with the glucocorticoid corticosterone to evaluate them as an animal model of depression. We then examined the gut microbial composition and brain and plasma metabolome in corticosterone-treated mice. Chronic corticosterone treatment resulted in reduced locomotor activity, increased anxiety-like and depression-related behaviors, decreased rotarod latency, reduced acoustic startle response, decreased social behavior, working memory deficits, impaired contextual fear memory, and enhanced cued fear memory. Chronic corticosterone treatment also altered the composition of gut microbiota, which has been reported to be associated with depression, such as increased abundance of Bifidobacterium, Turicibacter, and Corynebacterium and decreased abundance of Barnesiella. Metabolomic data revealed that long-term exposure to corticosterone led to a decrease in brain neurotransmitter metabolites, such as serotonin, 5-hydroxyindoleacetic acid, acetylcholine, and gamma-aminobutyric acid, as well as changes in betaine and methionine metabolism, as indicated by decreased levels of adenosine, dimethylglycine, choline, and methionine in the brain. These results indicate that mice treated with corticosterone have good face and construct validity as an animal model for studying anxiety and depression with altered gut microbial composition and brain metabolism, offering new insights into the neurobiological basis of depression arising from gut-brain axis dysfunction caused by prolonged exposure to excessive glucocorticoids.

Changes in Gut Microbial Composition and DNA Methylation in Obese Patients with NAFLD After Bariatric Surgery.

This study investigates the effects of bariatric surgery on non-alcoholic fatty liver disease (NAFLD) by examining the interplay between gut microbiota, epigenetics, and metabolic health. A cohort of 22 patients undergoing sleeve gastrectomy (SG) was analyzed for changes in gut microbial composition and DNA methylation profiles before and six months after surgery. Correlations between gut microbial abundance and clinical markers at baseline revealed that certain genera were associated with worse metabolic health and liver markers. Following SG, significant improvements were observed in the clinical, anthropometric, and biochemical parameters of the NAFLD patients. Although alpha-diversity indices (i.e., Chao1, Simpson, Shannon) did not show significant changes, beta-diversity analysis revealed a slight shift in microbial composition (PERMANOVA, p = 0.036). Differential abundance analysis identified significant changes in specific bacterial taxa, including an increase in beneficial Lactobacillus species such as Lactobacillus crispatus and Lactobacillus iners and a decrease in harmful taxa like Erysipelotrichia. Additionally, DNA methylation analysis revealed 609 significant differentially methylated CpG sites between the baseline values and six months post-surgery, with notable enrichment in genes related to the autophagy pathway, such as IRS4 and ATG4B. The results highlight the individualized responses to bariatric surgery and underscore the potential for personalized treatment strategies. In conclusion, integrating gut microbiota and epigenetic factors into NAFLD management could enhance treatment outcomes, suggesting that future research should explore microbiome-targeted therapies and long-term follow-ups on liver health post-surgery.

Modulation of gut microbiome in response to the combination of Escherichia coli Nissle 1917 and sugars: a pilot study using host-free system reflecting impact on interpersonal microbiome.

The differential effects of probiotic, prebiotic, and synbiotic formulations on human health are dictated by the inter-individual gut microbial profile. The effects of probiotics such as Escherichia coli Nissle 1917 (ECN) on gut microbiota may vary according to the microbiome profiles of individuals and may be influenced by the presence of certain carbohydrates, which can impact microbial community structure and treatment results. Processed fecal samples from donors having contrasting lifestyles, dietary patterns, and disease histories were mixed with 5 × 106 CFU/mL ECN with or without 1% (w/v) sugars (glucose, galactose, or rice starch) in a host-free system. Post-incubation, 16 s rRNA sequencing was performed. Microbial diversity and taxonomic abundance were computed in relation to the probiotic, prebiotic, and synbiotic treatment effects and interpersonal microbiome variance. Baseline gut microbial profiles showed significant inter-individual variations. ECN treatment alone had a limited impact on the inter-personal gut microbial diversity and abundance. Prebiotics caused a substantial enrichment in Actinobacteria, but there were differences in the responses at the order and genus levels, with enrichment shown in Bifidobacterium, Collinsella, and Megasphaera. Subject B exhibited enrichment in Proteobacteria and Cyanobacteria, but subject A showed more diversified taxonomic alterations as a consequence of the synbiotic treatments. Despite negligible difference in the α-diversity, probiotic, prebiotic, and synbiotic treatments independently resulted in distinct segregation in microbial communities at the β-diversity level. The core microbiota was altered only under prebiotic and synbiotic treatment. Significant correlations primarily for minor phyla were identified under prebiotic and synbiotic treatment. The interindividual microbiome composition strongly influences the effectiveness of personalized diet and treatment plans. The responsiveness to dietary strategies varies according to individual microbiome profiles influenced by health, diet, and lifestyle. Therefore, tailored approaches that consider individual microbiome compositions are crucial for maximizing gut health and treatment results.

Aged Gut Microbiome Induces Metabolic Impairment and Hallmarks of Vascular and Intestinal Aging in Young Mice.

Aging, an independent risk factor for cardiometabolic diseases, refers to a progressive deterioration in physiological function, characterized by 12 established hallmarks. Vascular aging is driven by endothelial dysfunction, telomere dysfunction, oxidative stress, and vascular inflammation. This study investigated whether aged gut microbiome promotes vascular aging and metabolic impairment. Fecal microbiome transfer (FMT) was conducted from aged (>75 weeks old) to young C57BL/6 mice (8 weeks old) for 6 weeks. Wire myography was used to evaluate endothelial function in aortas and mesenteric arteries. ROS levels were measured by dihydroethidium (DHE) staining and lucigenin-enhanced chemiluminescence. Vascular and intestinal telomere function, in terms of relative telomere length, telomerase reverse transcriptase expression and telomerase activity, were measured. Systemic inflammation, endotoxemia and intestinal integrity of mice were assessed. Gut microbiome profiles were studied by 16S rRNA sequencing. Some middle-aged mice (40-42 weeks old) were subjected to chronic metformin treatment and exercise training for 4 weeks to evaluate their anti-aging benefits. Six-week FMT impaired glucose homeostasis and caused vascular dysfunction in aortas and mesenteric arteries in young mice. FMT triggered vascular inflammation and oxidative stress, along with declined telomerase activity and shorter telomere length in aortas. Additionally, FMT impaired intestinal integrity, and triggered AMPK inactivation and telomere dysfunction in intestines, potentially attributed to the altered gut microbial profiles. Metformin treatment and moderate exercise improved integrity, AMPK activation and telomere function in mouse intestines. Our data highlight aged microbiome as a mechanism that accelerates intestinal and vascular aging, suggesting the gut-vascular connection as a potential intervention target against cardiovascular aging and complications.

Disordered Gut Microbiome and Alterations in Metabolic Patterns Are Associated With Hypertensive Left Ventricular Hypertrophy.

Left ventricular hypertrophy (LVH) is most common when driven by hypertension, and it is a strong independent risk factor for adverse cardiovascular events and death. Some animal models support a role for gut microbiota and metabolites in the development of LVH, but cohort studies confirming these findings in populations are lacking. We investigated the alterations of gut microbiota and metabolites in 30 patients with hypertension, 30 patients with hypertensive LVH, and 30 matched controls on the basis of 16S rDNA and metabolomic analyses. Thirty stool and 90 serum samples were collected in fasting conditions. ANOVA/Kruskal-Wallis/Pearson's χ2/Fisher's exact test and Bonferroni's correction were used (P<0.0167) for comparison among the 3 groups. A regression analysis and subgroup analysis were performed between gut microbiota and left ventricular mass index (LVMI) and metabolites and LVMI, respectively. Spearman correlation analysis was performed between metabolites and flora and metabolites and LVMI. We observed LVH-enriched Faecalitalea (β=6758.55 [95% CI, 2080.92-11436.18]; P=0.009), Turicibacter (β=8424.76 [95% CI, 2494.05-14355.47]; P=0.01), Ruminococcus torques group (β=840.88 [95% CI, 223.1-1458.67]; P=0.013), and Erysipelotrichaceae UCG-003 (β=856.37 [95% CI, 182.76-1529.98]; P=0.019) were positively correlated with LVMI. A total of 1141 (in sera) and 2657 (in feces) metabolites were identified. There was a sex-specific association between metabolites and LVMI. Significant changes in metabolic pathways in LVH were also observed, especially bile acid and lipid metabolism pathways. Our study demonstrated the disordered gut microbiota and microbial metabolite profiles in LVH. This highlights the roles of gut bacteria and metabolite in this disease and could lead to new intervention, diagnostic, or management paradigms for LVH. URL: https://www.chictr.org.cn; Unique Identifier: ChiCTR2200055603.