Roseburia Intestinalis Research Articles

Functional associations of the gut microbiome with dopamine, serotonin, and BDNF in schizophrenia: a pilot study

BackgroundSchizophrenia is a complex neuropsychiatric disorder with various etiologic factors. Aberrant levels of neurotransmitters or growth factors such as dopamine, serotonin, and BDNF have been shown to cause cognitive impairment in schizophrenia. Recently, the gut microbiome has also been suggested as a factor in the development of the disorder. To explore this potential link, we conducted a pilot study to examine the relationship between the gut microbiome and plasma levels of neurotransmitters and growth factors in schizophrenia. Shotgun metagenome sequencing of total RNA from fecal samples were used to profile the gut microbiome of schizophrenia patients (SCZ) and healthy controls (HC). The MetaPhlAn2 and HUMaN2 pipelines were used for bioinformatic analyses. ELISA was used to measure the plasma levels of dopamine, serotonin, and BDNF. Spearman’s rank correlation coefficient was used for correlation analysis.ResultsWe found that butyrate-producing bacteria were enriched in HC, whereas succinate-producing bacteria, namely Phascolarctobacterium succinatutens and Paraprevotella clara, were enriched in SCZ. The gut microbiota of SCZ was enriched in lipid biosynthesis pathways related to bile-resistant bacteria, whereas phospholipid pathways linked with butyrate-producing bacteria were enriched in HC. Alistipes indistinctus, Dorea longicatena, and Roseburia inulinivorans were negatively correlated with dopamine levels. Roseburia intestinalis and Parabacteroides goldsteini were negatively correlated with serotonin and BDNF levels, respectively. We found a significant correlation between dopamine and serotonin levels, and the super-pathway of purine deoxyribonucleoside degradation.ConclusionsThis study provides further support that gut microbiota could modulate neurotransmitter levels. The results suggest that gut microbiome-targeted therapies may help to rebalance neurotransmitter levels, offering new hope for the treatment of schizophrenia.

Microbially-produced folate forms support the growth of Roseburia intestinalis but not its competitive fitness in fecal batch fermentations

BackgroundFolate (vitamin B9) occurs naturally mainly as tetrahydrofolate (THF), methyl-tetrahydrofolate (M-THF), and formyl-tetrahydrofolate (F-THF), and as dietary synthetic form (folic acid). While folate auxotrophy and prototrophy are known for several gut microbes, the specific folate forms produced by gut prototrophs and their impact on gut auxotrophs and microbiota remain unexplored.MethodsHere, we quantified by UHPLC-FL/UV folate produced by six predicted gut prototrophs (Marvinbryantia formatexigens DSM 14469, Blautia hydrogenotrophica 10507 T, Blautia producta DSM 14466, Bacteroides caccae DSM 19024, Bacteroides ovatus DSM 1896, and Bacteroides thetaiotaomicron DSM 2079 T) and investigated the impact of different folate forms and doses (50 and 200 µg/l) on the growth and metabolism of the gut auxotroph Roseburia intestinalis in pure cultures and during fecal anaerobic batch fermentations (48 h, 37 °C) of five healthy adults.ResultsOur results confirmed the production of folate by all six gut strains, in the range from 15.3 ng/ml to 205.4 ng/ml. Different folate forms were detected, with THF ranging from 12.8 to 41.4 ng/ml and 5-MTHF ranging from 0.2 to 113.3 ng/ml, and being detected in all strains. Natural folate forms, in contrast to folic acid, promoted the growth and metabolism of the auxotroph R. intestinalis L1-82, with dose-dependent effects. During fecal batch fermentations, folate forms at both levels had no detectable effect on total bacteria concentration, on gut community composition and metabolic activity and on Roseburia spp. abundance, compared to the control without folate addition.ConclusionsOur study demonstrates for the first time in vitro the production of different natural folate forms by predicted gut prototrophs and the stimulation on the growth of the folate auxotrophic butyrate-producing R. intestinalis L1-82. Surprisingly, folate did not impact fecal fermentations. Our data suggest that the dietary folate forms at the tested levels may only have limited effects, if any, on the human gut microbiota in vivo.

Multi-omics analysis of gut-brain axis reveals novel microbial and neurotransmitter signatures in patients with arteriosclerotic cerebral small vessel disease

Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.

Metagenomics Analysis Reveals Unique Gut Microbiota Signature of Slow-Transit Constipation.

Altered gut microbiota may play a role in slow-transit constipation (STC). We conducted a study of gut microbiota composition and functionality in STC using metagenomic analyses. We assembled a clinical cohort of 24 patients with STC physiology age- and sex-matched to 24 controls. We performed shotgun metagenomic sequencing followed by prediction of metabolite composition from functional profiles. In a middle-aged (mean 55.3 years), predominantly female cohort, there were no significant differences in α-diversity indices, but permutational multivariate analysis of variance analysis showed significant between-group differences (R 2 = 0.050, P < 0.001) between STC patients and controls. Gordonibacter pamelaeae , Bifidobacterium longum , Firmicutes bacterium co-abundance gene group 94, and Anaerotruncus colihominis were more abundant in STC, whereas Coprococcus comes and Roseburia intestinalis were more abundant in controls. Gut-derived metabolites varying in STC relative to controls were related to bile acid and cholesterol metabolism. We found a unique metagenomic and metabolomic signature of STC.

Gut microbiome structure and function in asymptomatic diverticulosis

BackgroundColonic diverticulosis, the most common lesion found in routine colonoscopy, affects more than 50% of individuals aged ≥ 60 years. Emerging evidence suggest that dysbiosis of gut microbiota may play an important role in the pathophysiology of diverticular disease. However, specific changes in microbial species and metabolic functions in asymptomatic diverticulosis remain unknown.MethodsIn a cohort of US adults undergoing screening colonoscopy, we analyzed the gut microbiota using shotgun metagenomic sequencing. Demographic factors, lifestyle, and medication use were assessed using a baseline questionnaire administered prior to colonoscopy. Taxonomic structures and metabolic pathway abundances were determined using MetaPhlAn3 and HUMAnN3. We used multivariate association with linear models to identify microbial species and metabolic pathways that were significantly different between asymptomatic diverticulosis and controls, while adjusting for confounders selected a priori including age at colonoscopy, sex, body mass index (BMI), and dietary pattern.ResultsAmong 684 individuals undergoing a screening colonoscopy, 284 (42%) had diverticulosis. Gut microbiome composition explained 1.9% variation in the disease status of asymptomatic diverticulosis. We observed no significant differences in the overall diversity of gut microbiome between asymptomatic diverticulosis and controls. However, microbial species Bifidobacterium pseudocatenulatum and Prevotella copri were significantly enriched in controls (q value = 0.19 and 0.14, respectively), whereas Roseburia intestinalis, Dorea sp. CAG:317, and Clostridium sp. CAG: 299 were more abundant in those with diverticulosis (q values = 0.17, 0.24, and 0.10, respectively). We observed that the relationship between BMI and diverticulosis appeared to be limited to carriers of Bifidobacterium pseudocatenulatum and Roseburia intestinalis (Pinteraction = 0.09).ConclusionsOur study provides the first large-scale evidence supporting taxonomic and functional shifts of the gut microbiome in individuals with asymptomatic diverticulosis. The suggestive interaction between gut microbiota and BMI on prevalent diverticulosis deserves future investigations.

Intestinal microbiota in children with chronic viral hepatitis

The article is devoted to a review of the literature on the study of intestinal microbiota in chronic viral hepatitis in children. The results of recent studies of microbial diversity of colon contents using 16S ribosomal RNA sequencing are presented. Scientific research in recent years has proven the influence of changes in the microbiota and its individual representatives on the formation of complications in patients with chronic viral hepatitis, the development of fibrosis/cirrhosis. Changed quantitative and species ratios of microorganisms can lead to the launch of pathological reactions in the intestinal-liver axis system. A significant reduction in the number of bacteria such as Clostridia and Bacteroidia (Faecalibacterium, Roseburia inilinivorans, Roseburia intestinalis, Coprococcus comes) causes low production of short-chain fatty acid butyrate, which can interfere with the functioning of tight junction proteins. Leaks and increased intestinal permeability create conditions for the formation of inflammation due to the activity of pro-inflammatory cytokines. Violation of the intestinal barrier function creates the opportunity for the penetration of bacteria, lipopolysaccharide complexes, bacterial ligands and metabolites, leading to the development of immunopathological reactions. These changes in the pediatric population are less noticeable than in the adult cohort of patients, since the clinical course of chronic viral hepatitis in children has a smoother course. However, periods of exacerbation, which are characterized by clinical and laboratory changes, may maintain the risk of developing fibrogenesis activity in older age groups. Data on intestinal microbial diversity in adult patients with chronic viral hepatitis B and C are presented separately. The possibilities of using pre- and probiotic therapy in the complex treatment of chronic liver diseases in adults and children are considered.

Roseburia intestinalis-derived extracellular vesicles ameliorate colitis by modulating intestinal barrier, microbiome, and inflammatory responses.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)-derived EVs (R-EVs) as potent anti-inflammatory mediators in treating dextran sulfate sodium-induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R-EVs with a 76nm diameter were isolated from R using a tangential flow filtration system. Orally administered R-EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile-Pro-Ile in the vesicular structure, R-EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP-1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.

P-324 Finding on the gut microbiome impact on non-reproductive pathologies of the uterus: an endometriosis perspective

Abstract Study question Is there any link between intestinal microbiome and endometriosis? Summary answer The aetiopathogenesis of endometriosis might be linked to intestinal dysbiosis. Microorganisms could be used as potential microbiota-mediated metabolites therapy to target the estrobolome in endometriosis. What is known already Endometriosis (EMs) is a chronic estrogenic-dependent gynaecological condition with a complex and multifactorial aetiology, characterized by the presence of endometrial glands and endometrial-like tissue outside the uterus, accompanied by a severe inflammatory process. Sampson’s theory of retrograde menstruation is considered one of the most convincing hypotheses for the origin of EMs. Recently, the human microbiome has been linked to its pathogenesis, and exits some evidence that it might modulate the immune system from the gut, therefore the generation of a dysfunctional immune response caused by intestinal dysbiosis might play an important role in the initiation and progression of EMs. Study design, size, duration A case-control study was designed to analyse intestinal microbiome from EMs patients and age-matched healthy women. Herein, we aim to investigate for potential intestinal biomarkers related to the pathology. The recruitment was through health questionnaires such as EHP-5 setting the initial cohort at 243 women. This initial cohort was screened according to inclusion and exclusion criteria. Participants/materials, setting, methods Seventy-seven women met eligibility criteria and were enrolled in the study. Stool samples from the controls group (n = 43) and patients with a positive diagnosis of EMs (n = 34) were collected and subjected to 16S rRNA gene sequencing using the V3-V4 regions. Various multivariate analysis approaches were used to assess diversity, composition and abundance of intestinal microbiota. Main results and the role of chance The number of significantly different taxa between healthy controls and EMs patients were 18 (p-value&amp;lt;0.05). Among these 18 taxa, we found 3 families: Bacteroidaceae, Lactobacillaceae and Desulfovibrionaceae; 3 genera: Blautia, Anaerostipes and Lachnospira; and 12 species: Roseburia intestinalis, Bacteroides uniformis, Anaerobutyricum hallii, among others), with a higher diversity of families and genera in the patient group, while the control group had a higher diversity of species, according to the results of Shannon and Simpsońs indexes. This suggests that EMs is dominated by a few species belonging to a wide variety of families and genera, while in the control group there is a greater variability of intestinal species belonging to a smaller number of families and genera. These taxa were related with molecular routes implied in the management of inflammation and estrogens signalling. Additionally, the data were correlated with clinical parameters through the Endometriosis Health Profile-5 questionnaire (EHP-5). This correlation shows significant differences specifically into the «self-image» variable and the total score with the genus diversity (positive and negative correlations were reported), with a strong positive correlations between the variable “Infertility” and the genus Anaerostipes. Limitations, reasons for caution Pronacera develops molecular tests for several conditions that involve the analysis of genes, proteins, and microbes in human samples. Neither the patients nor the healthcare professionals participating in this study have been paid or influenced whatsoever. Hence, the authors report no other potential conflicts of interest. Wider implications of the findings The aetiopathogenesis of EMs might be linked to intestinal dysbiosis. In this sense, the taxa identified in this study and its estrobolome-related metabolite could play a key role in the initiation of the disease, proposing themselves as potential prognostic, diagnostic and therapeutic targets for the future. Trial registration number not applicable

Impact of high-fat diet on ovarian epigenetics: Insights from altered intestinal butyric acid levels

ObjectiveTo investigate the effects of a high-fat diet (HFD) on the gut bacterium Roseburia intestinalis and butyric acid levels, and to assess their impact on ovarian function and epigenetic markers in mice. MethodsA total of 20 female ICR mice aged 4 weeks were randomly assigned to two groups and fed either a control diet (CD) or an HFD for 36 weeks. Post-intervention, ileal contents were analyzed for the quantification of butyric acid using ELISA, while feces were obtained for Roseburia intestinalis expression assessment via qPCR. Histological evaluations of intestinal and ovarian tissues included H&E and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining, alongside immunohistochemical analysis for F4/80, and immunofluorescent detection of Occludin, ZO-1, 5 mC, and H3K36me3. Ovarian health was assessed through follicle counts and morphological evaluations. Statistical analyses were performed using GraphPad Prism 8.0, with P < 0.05 considered significant. ResultsAfter 36 weeks, the HFD group showed significantly higher body weight compared to the CD group (P < 0.01). The HFD led to a decrease in Roseburia intestinalis and butyric acid levels, a reduction in intestinal goblet cells, and an increase in intestinal inflammation. Histological analyses revealed impaired ovarian follicular development and enhanced inflammation in the HFD mice, with immunofluorescent staining showing downregulation of the ovarian epigenetic markers 5 mC and H3K36me3. ConclusionOur study demonstrates that long-term HFD negatively impacts ovarian function and epigenetic regulation. We found decreased levels of the gut bacterium Roseburia intestinalis and its metabolite, butyric acid, which contribute to these adverse effects. Additionally, the associated intestinal inflammation and compromised mucosal barrier may contribute to these adverse outcomes on female reproductive health.

Meta-analysis of shotgun sequencing of gut microbiota in Parkinson’s disease

We aimed to identify gut microbial features in Parkinson’s disease (PD) across countries by meta-analyzing our fecal shotgun sequencing dataset of 94 PD patients and 73 controls in Japan with five previously reported datasets from USA, Germany, China1, China2, and Taiwan. GC-MS and LC-MS/MS assays were established to quantify fecal short-chain fatty acids (SCFAs) and fecal polyamines, respectively. α-Diversity was increased in PD across six datasets. Taxonomic analysis showed that species Akkermansia muciniphila was increased in PD, while species Roseburia intestinalis and Faecalibacterium prausnitzii were decreased in PD. Pathway analysis showed that genes in the biosyntheses of riboflavin and biotin were markedly decreased in PD after adjusting for confounding factors. Five out of six categories in carbohydrate-active enzymes (CAZymes) were decreased in PD. Metabolomic analysis of our fecal samples revealed that fecal SCFAs and polyamines were significantly decreased in PD. Genes in the riboflavin and biotin biosyntheses were positively correlated with the fecal concentrations of SCFAs and polyamines. Bacteria that accounted for the decreased riboflavin biosynthesis in Japan, the USA, and Germany were different from those in China1, China2, and Taiwan. Similarly, different bacteria accounted for decreased biotin biosynthesis in the two country groups. We postulate that decreased SCFAs and polyamines reduce the intestinal mucus layer, which subsequently facilitates the formation of abnormal α-synuclein fibrils in the intestinal neural plexus in PD, and also cause neuroinflammation in PD.

Roseburia intestinalis Supplementation Could Reverse the Learning and Memory Impairment and m6A Methylation Modification Decrease Caused by 27-Hydroxycholesterol in Mice.

The abnormality in N6-methyladenosine (m6A) methylation is involved in the course of Alzheimer's disease (AD), while the intervention of 27-Hydroxycholesterol (27-OHC) can affect the m6A methylation modification in the brain cortex. Disordered gut microbiota is a key link in 27-OHC leading to cognitive impairment, and further studies have found that the abundance of Roseburia intestinalis in the gut is significantly reduced under the intervention of 27-OHC. This study aims to investigate the association of 27-OHC, Roseburia intestinalis in the gut, and brain m6A modification in the learning and memory ability injury. In this study, 9-month-old male C57BL/6J mice were treated with antibiotic cocktails for 6 weeks to sweep the intestinal flora, followed by 27-OHC or normal saline subcutaneous injection, and then Roseburia intestinalis or normal saline gavage were applied to the mouse. The 27-OHC level in the brain, the gut barrier function, the m6A modification in the brain, and the memory ability were measured. From the results, we observed that 27-OHC impairs the gut barrier function, causing a disturbance in the expression of m6A methylation-related enzymes and reducing the m6A methylation modification level in the brain cortex, and finally leads to learning and memory impairment. However, Roseburia intestinalis supplementation could reverse the negative effects mentioned above. This study suggests that 27-OHC-induced learning and memory impairment might be linked to brain m6A methylation modification disturbance, while Roseburia intestinalis, as a probiotic with great potential, could reverse the damage caused by 27-OHC. This research could help reveal the mechanism of 27-OHC-induced neural damage and provide important scientific evidence for the future use of Roseburia intestinalis in neuroprotection.

Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity

The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R.intestinalis does not directly produce HVA, it enhances B.longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B.longum, or R.intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.

Microbiome composition recovery after liver transplantation correlates with initial liver disease severity and antibiotics treatment

Liver transplantation (LT) is crucial for end-stage liver disease, but it is linked to infection risks. Pathobionts, microorganisms potentially harmful under specific conditions, can cause complications posttransplant. Monitoring such pathogens in fecal samples can be challenging and therefore remains underexplored post-LT. This study aimed to analyze the gut microbiome before and after LT, tracking pathobionts and correlating clinical data. The study involved 17 liver transplant recipients, 17 healthy relatives (spouses), and 13 donors. Gut samples collected pretranplantation and posttransplantation underwent bacterial and fungal profiling through DNA sequencing. Quantitative polymerase chain reaction was used to assess microbial load. Statistical analyses included alpha and beta diversity measures, differential abundance analysis, and correlation tests between microbiome and clinical parameters. Microbiome analysis revealed dynamic changes in diversity posttransplant. Notably, high-severity patients showed persistent and greater dysbiosis during the first months post-LT compared with low-severity patients, partly due to an antibiotic treatment pre-LT. The analysis identified a higher proportion of pathogens such as Escherichia coli/Shigella flexneri in high-severity cases posttransplant. Furthermore, butyrate producers including Roseburia intestinalis, Anaerostipes hadrus, and Eubacterium coprostanoligenes were positively correlated with levels of albumin. This study offers valuable insights into post-LT microbiome changes, shedding light on the need for tailored prophylactic treatment post-LT.

Abstract P386: Associations of Gut Microbiome, but Not Microbial Metabolites, With Hypertension Differ by Race: Findings From the Baltimore Longitudinal Study of Aging

Introduction: Social determinants of health (SDoH) are thought to drive race disparities in hypertension (HTN) and in the gut microbiome (GMB). Additionally, studies suggest that associations of GMB and microbial metabolites with HTN differ by race. Whether this effect modification persists after accounting for SDoH factors has not been investigated. Hypothesis: Race-specific associations of GMB and microbial metabolites with HTN are attenuated when accounting for SDoH factors. Methods: We selected N=100 Baltimore Longitudinal Study of Aging participants for a fecal metabolomics study. We grouped participants by self-reported race (Black or White) and HTN status (HTN: SBP/DBP ≥ 130/80 mmHg without anti-HTN medication vs. normal blood pressure: SBP/DBP &amp;lt; 120/80), with matching on age, sex, and BMI category. After removal for missing SDoH data, we had N=95 participants for analysis. Metabolon measured fecal metabolites using their global, untargeted panel. Diversigen measured fecal GMB features (diversity, composition, and functional potential) using shotgun metagenomic sequencing. We tested univariable and multivariable associations of GMB alpha diversity and microbial metabolites with HTN using logistic regression, GMB beta diversity with HTN using PERMANOVA, and microbial species and functional potential with HTN using ANCOM-BC and MaAsLin2 methods, respectively. We analyzed associations overall and stratified by race. We adjusted for upstream (employed for pay, income meets needs, marital status, household size, educational attainment) and midstream (stress and depression scores, alternative healthy eating index, total calories, physical activity, smoking, and having private health insurance) SDoH factors. Results: HTN groups did not differ by age (66.3±11.1 years), sex (N=62/95 female), BMI (28.6±4.9 kg/m 2 ), or race (N=45/95 Black). Carnitine, a precursor for bacterial trimethylamine N-oxide (TMAO), was inversely associated with HTN (OR: 0.30; 95%CI [0.13,0.61]) and was not modified by race. Among GMB features, abundance of Roseburia intestinalis was lower among those with HTN (logfold-change [LFC]: -3.53, p=0.0132). Race modified associations of GMB evenness and Shannon diversity with hypertension, with effects generally being stronger among White participants (e.g.: Shannon Black OR [95%CI]: 0.99 [0.59,1.65]; White OR [95%CI]: 1.33 [0.87,2.86], interaction p=0.0242). Race also modified associations of bacterial species with HTN, including Roseburia intestinalis, which was stronger for White (LFC: -4.44) than for Black (LFC: -0.40) participants. Adjustment for SDoH factors did not attenuate effect modification of associations by race. Conclusions: In our study, which was balanced on race and HTN status (without medications), race modified associations of GMB diversity and composition with HTN, and this was not attenuated by SDoH factors.

Abstract MP01: Life-Course Socioeconomic Status and the Gut Microbiome in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: Socioeconomic status (SES) in childhood and beyond may influence the gut microbiome (GMB), with implications for disease risk. Studies evaluating the relationship between life-course SES and the gut microbiome (GMB) are sparse, particularly among Hispanic/Latino individuals, who have a high prevalence of low SES. Hypothesis: Low life-course SES indicators are associated with less diversity and overall composition of the gut microbiome in United States (U.S.) Hispanic/Latino adults. Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multi-site population-based cohort study conducted in the U.S. Childhood sanitation conditions (plumbing, sewer/septic tank), childhood SES (parental education and childhood hardship), adulthood neighborhood SES, and adulthood SES (education, income, and economic hardship) were used as life-course SES indicators. Shotgun sequencing was performed on stool samples (n=1057). Alpha-diversity was measured by the Shannon diversity index. Permutational multivariate analysis of variance was used to assess the association of SES indicators with overall microbiome composition, as measured using the Jensen-Shannon Divergence distance. Analysis of Compositions of Microbiomes was used to identify associations of life-course SES indicators with GMB species, adjusting for age, sex, BMI, U.S. or foreign-born, study center, Hispanic/Latino background, type of stool, diet quality, smoking, alcohol consumption, depressive and anxiety symptoms, diabetes, hypertension, cardiovascular disease, dyslipidemia, and antibiotic use. Results: Low sanitation and low SES during childhood were reported by 32% (342 of 1053) and 37% (330 of 884) of participants, respectively. In adulthood, 56% (585 of 1053) lived in a low SES neighborhood and 45% (447 of 1002) had low SES. Life-course SES indicators were not associated with GMB diversity. However, overall microbiome composition differed significantly according to childhood SES (R2 =0.28%, P = 0.04). Low childhood sanitation was associated with higher abundance of Ruminococcus torques and Clostridium lactatifermentans , and depleted abundance of Prevotella species. Low childhood SES was associated with higher abundance of species from genus Streptococcus (S. salivarius, S. parasanguinis, and S. infantis), Veillonella parvula, Prevotella stercorea, and Roseburia intestinalis. Low adulthood SES was associated with depleted abundance of species from Bacteroides, and living in a low adulthood neighborhood SES was associated with depleted abundance of species from Rikenella . Conclusion: Low childhood SES was associated with an altered GMB composition in U.S. Hispanic/Latino adults. Early-life SES may have long-term effects on GMB composition, underscoring another biological mechanism linking early childhood factors to adulthood disease.

P852 Metataxonomic and metabolomic profiling to predict response to anti-TNF therapy in Crohn’s Disease

Abstract Background The composition of the gut microbiota is associated with response to treatments in inflammatory bowel disease1. We sought to identify gut microbial and metabolomic biomarkers associated with response to anti-TNF therapy in Crohn’s disease. Methods Faecal and serum samples collected at baseline and week 14 of anti-TNF treatment in the "Predictors of anti-TNF treatment failure" (PANTS) study were used2. Response to treatment (defined clinically and biochemically) was determined at week 142. Faecal samples were processed by GA-map®, with targeted 16S rRNA PCR sequencing. Serum samples were analysed with targeted liquid chromatography tandem mass spectrometry for bile acids and tryptophan metabolites. Multivariate and univariate analyses, as well as Spearman’s rank test, were performed. Results Two-hundred and twenty-four patients with Crohn’s disease commencing anti-TNF therapy were included (54.1% anti-TNF responders, 48.6% female, median age 37.2 (26.5-50.0) years, 56.9% receiving immunomodulator-based treatment). A significantly higher proportion of non-responders received corticosteroid treatment compared to responders at baseline (p=0.0009). Sixty-nine bacterial taxa were identified. Significantly lower abundances of Clostridium difficile and Mycoplasma were identified in responders relative to non-responders at baseline (q-value=0.046 and q-value=0.034, respectively). No significant differences in the abundances of Faecalibacterium prausnitzii, Shigella or Escherichia Coli were found (all q-values &amp;gt; 0.05). Eighteen serum bile acids and thirteen tryptophan metabolites were identified. Significantly higher serum abundances of cholic acid, tryptophan and 3OH-kynurenine were identified in responders at baseline (q-values=0.049, 0.033, and 0.033, respectively). Exploration of microbial–metabolite associations revealed negative correlations between secondary bile acids and several bile salt hydrolase producing bacteria, such as Bifidobacterium (r ≤ -0.50). Positive correlations were also identified between xanthurenic acid and Bifidobacterium and Roseburia intestinalis (r ≥ 0.50). Increased abundances of short-chain fatty acid producing bacteria, such as Bifidobacterium and Bacteroides vulgatus, were noted in responders at week 14. Conclusion We have identified baseline differences in the faecal microbiota and serum metabolome of anti-TNF responders and non-responders. These findings require validation in larger cohorts to determine their robustness for potential use in treatment personalisation.

P060 Increased metabolic activity of faecal Sutterella Wadsworthensis at IBD onset is associated with an increased risk of escalation to biologic therapies - Results from the Birimingham Inception Cohort Study

Abstract Background Gut microbiome disruption is an established characteristic of IBD. The lack of treatment naïve longitudinal microbiome data makes it challenging to separate the influence of potential confounders. We present detailed stool metagenomics analysis from a treatment naïve cohort of IBD patients seen in our rapid-access IBD inception clinic. Methods Stool collected in DNA Genotek OM-200 kits was collected pre-diagnosis, alongside a faecal calprotectin (FCP). Microbial DNA was extracted. Libraries were prepared using NEBNext Ultra II FS DNA Library Prep Kit, NEBNext Multiplex Oligos and sequenced using an Illumina NextSeq550. Data processing was undertaken using the HUMAnN 3.0 workflow. After quality control, a median of 3.6 million reads per sample were obtained. Abundance was mapped to the ChocoPhlAn database and functional pathways derived from MetaCyc. Diversity analysis was undertaken in Vegan, with MaAsLin2 for taxa differences. A False discovery Rate (FDR) &amp;lt;0.2 was considered relevant, &amp;lt;0.05 highly significant. Results A total of 45 CD and 33 UC inception patients were included. There was no significant difference in alpha diversity (Shannon; UC median 2.58[IQR 0.8], CD 2.69[1.04] p=0.36) or differential clustering for beta diversity. Shannon alpha diversity significantly associated with FCP across IBD (n=74, Spearman’s Rho [SR] -0.33 p=0.004) and endoscopic severity in both IBD subtypes (UCEIS n=30 SR -0.37 p=0.047, SESCD n=44 SR -0.35 p=0.016). Across IBD, patients going on to require biologic therapy had a significantly lower baseline Shannon (BioYes 2.26[0.98], BioNo 2.77[0.88] p=0.02, split by IBD subtype in Figure 1). Across IBD, increased FCP associated with depletion of two strains of Faecalibacterium Prausnitzii (SGB15318, log2 fold change[L2FC] -1.2 FDR 0.09; SGB15342 L2FC -1.1 FDR 0.15) alongside Roseburia Intestinalis (SGB4951 L2FC -0.7 FDR 0.09). R.Intestinalis also negatively correlated with Harvey Bradshaw Index (L2FC -0.93 FDR 0.02), whilst F.Prausnitzii (SGB15342) did with UCEIS (L2FC -2.3 FDR 0.05). 82 metabolic pathways correlated with UCEIS (FDR &amp;lt;0.2, 8 &amp;lt;0.05), with 89 for SESCD (6 &amp;lt;0.05). Increased activity of Sutterella Wadsworthensis associated positively with UCEIS (5 pathways). On initial comparison across IBD, no significant signal was seen for future biologic utilisation. However, if analyses were corrected for baseline inflammation (derived by FCP), increased activity of S.Wadsworthensis was again seen (Table 1). Conclusion Reduced alpha diversity at IBD onset associated with increased disease severity and future utilisation of biologic treatment. Increased activity of S.Wadsworthensis associated with an increased risk of future biologic requirement above that explained by mucosal inflammation alone.

Effect of dark sweet cherry (Prunus avium) supplementation on the fecal microbiota, metabolic endotoxemia, and intestinal permeability in obese subjects: a single-blind randomized trial.

This single blind placebo-controlled study has as its main objectives to investigate the influence of dark sweet cherries (DSC) consumption on obesity-related dysbiosis, metabolic endotoxemia, and intestinal permeability. Participants (>18 years old, BMI: 30-40 kg m-2) consumed 200 mL of DSC juice with 3 g of DSC powder (n = 19) or a placebo drink (n = 21) twice per day for 30 days. The gut microbiota abundance was investigated using 16S ribosomal RNA sequencing on fecal DNA. Metabolic endotoxemia was evaluated by measuring lipopolysaccharide-binding protein (LBP) in fasting plasma samples. Intestinal permeability was assessed using the lactulose/mannitol (L/M) test and by measuring regeneration islet-derived protein 4 (REG4), and interleukin-22 (IL-22) mRNA levels in stool samples. Results showed that DSC supplementation decreased the abundance of Anaerostipes hadrus (p = 0.02) and Blautia (p = 0.04), whose changes were significant in BMI ≥ 35 participants (p = 0.004 and p = 0.006, respectively). Additionally, DSC prevented the increase of Alistipes shahii (p = 0.005) and Bilophila (p = 0.01) compared to placebo. Notably, DSC intervention favored the abundance of bacteria supporting a healthy gut ecosystem such as Roseburia intestinalis (p = 0.01), Turicibacter (p = 0.01), and Bacteroides vulgatus (p = 0.003) throughout the intervention, along with Clostridium leptum (p = 0.03) compared to placebo. The LBP, L/M ratio, REG-4 and IL-22 mRNA levels remained unchanged in placebo and cherry groups, implying that participants did not experience alterations in intestinal permeability. These findings highlight the potential gut-health benefits of DSC and encourage future research among individuals with BMI ≥ 35 and increased intestinal permeability.

Liver Bacterial Colonization in Patients with Obesity and Gut Dysbiosis.

Recently, the link between gut microbiota, liver inflammation, and obesity has become an interesting focus of research. The aim of this study is to show the possible relation between gut microbiota dysbiosis in patients with obesity and the presence of bacterial genomes in their liver biopsies. A prospective study on patients undergoing bariatric surgery was carried out. Anthropometric and metabolic data, comorbidities, stool samples, and hepatic biopsies were collected and analyzed at the time of surgery. The V3-16S rRNA region was sequenced using the Ion Torrent new-generation sequencing platform. In each of the 23 patients enrolled, the bacterial population was analyzed both in the stools and liver. In eight patients (34.7%), Prevotella (62.5%), Bacteroides (50%), Streptococcus (12.5%), and Dalister (12.5%) were found in both samples, simultaneously; in 15 cases, the liver was free from colonization. The statistically significant difference between groups was a Roseburia intestinalis reduction in fecal samples of patients with liver biopsies colonized by bacteria (1% vs 3%; p = 0.0339). To the best of our knowledge, this is the first study reporting the presence of bacterial genome in a liver biopsy on bariatric patients, instead of the microbe-associated molecular patterns. Notably, in literature, the presence of Roseburia intestinalis in stool samples has been shown to prevent intestinal inflammation playing its role in the gut barrier integrity. In our population, the Roseburia reduction was associated with the presence of bacterial genome in the liver, probably related to a greater permeability of the gut and vascular barriers.

The association between flagellin producers in the gut microbiota and HDL-C level in humans

The gut microbiota can be beneficial and harmful to cardiovascular health depending on the mechanisms. The interaction between gut microbiota-derived flagellin and toll-like receptor 5 in hepatocytes, resulting in apolipoprotein A1 (ApoA1) production, brings forth a cardiovascular benefit to the host. Here, the association between flagellated microbiota and high-density lipoprotein-cholesterol (HDL-C) in humans was explored. Through sex-based gut microbiota analysis of two population-based cohorts, the 500 Functional Genomics Project (500FG) and Chinese cohorts, we found positive correlations between the capacity to produce flagellins in the gut microbiota and HDL-C in females of the 500FG and males of Chinese cohorts. Eubacterium rectale, Lachnospira pectinoschiza, Roseburia intestinalis and Roseburia inulinivorans were crucial species for such correlations. Diverse types of flagellins and TLR5, but not NAIP/NLRC4, flagellin-engaging receptors, were detectable by proteomic analysis of the human liver. However, not all flagellated bacteria yield the same degree of such benefit because of differences in the penetration of flagellins where other factors such as geographics and diets may play important roles.