Composition Of Gut Microbiome In Patients Research Articles

Impact of dance classes on motor and cognitive functions and gut microbiota composition in multiple sclerosis patients: Randomized controlled trial.

Evidence suggests that multiple sclerosis (MS) induces a decline in motor and cognitive function and provokes a shift in gut microbiome composition in patients. Therefore, the aim of the study was to explore the effect of dance classes on the motor and cognitive functions and gut microbiota composition of MS patients. In this randomized controlled trial, 36 patients were randomly divided into two groups: the experimental group (n=18) and the passive control group (n=18). Supervised rock and roll and sports dance classes were performed for 12weeks at a frequency of two times a week. Before and after the intervention, fecal samples were taken and the motor and cognitive function assessments were completed. Fecal microbiota were categorized using primers targeting the V3-V4 region of 16S rDNA. Our results revealed significant differences in mobility performance (T25-FWT), attention and working memory (TMT B), and finger dexterity (9-HPT) within the experimental group. Furthermore, we reported favorable shifts in gut microbial communities (an increase in Blautia stercoris and a decrease in Ruminococcus torques) within the experimental group. In conclusion, our randomized control trial on the effects of 12-week dance classes in MS patients found significant improvements in motor and cognitive functions, with further moderate influence on gut microbiota composition.

Impact of dance classes on motor and cognitive functions and gut microbiota composition in multiple sclerosis patients: Randomized controlled trial.

Evidence suggests that multiple sclerosis (MS) induces a decline in motor and cognitive function and provokes a shift in gut microbiome composition in patients. Therefore, the aim of the study was to explore the effect of dance classes on the motor and cognitive functions and gut microbiota composition of MS patients. In this randomized controlled trial, 36 patients were randomly divided into two groups: the experimental group (n=18) and the passive control group (n=18). Supervised rock and roll and sports dance classes were performed for 12weeks at a frequency of two times a week. Before and after the intervention, fecal samples were taken and the motor and cognitive function assessments were completed. Fecal microbiota were categorized using primers targeting the V3-V4 region of 16S rDNA. Our results revealed significant differences in mobility performance (T25-FWT), attention and working memory (TMT B), and finger dexterity (9-HPT) within the experimental group. Furthermore, we reported favorable shifts in gut microbial communities (an increase in Blautia stercoris and a decrease in Ruminococcus torques) within the experimental group. In conclusion, our randomized control trial on the effects of 12-week dance classes in MS patients found significant improvements in motor and cognitive functions, with further moderate influence on gut microbiota composition.

Two weeks of acarbose treatment shows no effect on gut microbiome composition in patients with type 2 diabetes: a randomised, placebo-controlled, double-blind, crossover study.

The alpha-glucosidase inhibitor acarbose is approved for the treatment of type 2 diabetes (T2D). It acts in the lumen of the gut by reducing intestinal hydrolysis and absorption of ingested carbohydrates. This reduces postprandial blood glucose concentration and increases the content of carbohydrates in the distal parts of the intestine potentially influencing gut microbiome (GM) composition and possibly impacting the gut microbiome (GM) dysbiosis associated with T2D. Here, we investigated the effect of acarbose on GM composition in patients with T2D. Faecal samples were collected in a previously conducted randomised, placebo-controlled, double-blind, crossover study in which 15 individuals with metformin-treated T2D (age 57-85 years, HbA1c 40-74 mmol/mol, BMI 23.6-34.6 kg/m2) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a 6-week wash-out period. Faecal samples were collected before and by the end of each treatment period. The GM profiles were evaluated by 16S rRNA gene amplicon sequencing. The GM profiles after the treatment periods with acarbose or placebo remained unaffected (P > 0.7) when compared with the GM profiles before treatment. This applied to the analysis of within-sample diversity (α-diversity) and between-sample bacterial composition diversity (β-diversity). Additionally, no dominant bacterial species differentiated the treatment groups, and only minor increases in the relative abundances of Klebsiella spp. and Escherichia coli (P < 0.05) were observed after acarbose treatment. In patients with metformin-treated T2D, 14 days of treatment with acarbose showed only minor effects on GM as seen in increased relative abundances of Klebsiella spp. and Escherichia coli.

Causal effects of gut microbiota on scoliosis: A bidirectional two-sample mendelian randomization study

BackgroundRecent studies have shown altered gut microbiome composition in patients with scoliosis. However, the causal effect of gut microbiota on scoliosis remains unknown. MethodsA Mendelian randomization (MR) study was conducted to quantify the impact of 191 gut microbiome taxa's instrumental variables from the MibioGen Genome-wide association study (GWAS) on scoliosis risk using data from the FinnGen GWAS (1168 cases and 16,4682 controls). Inverse variance weighted (IVW) was the main method, and MR results were verified by sensitive analysis. ResultsBilophila, Eubacterium (eligens group), Prevotella9, and Ruminococcus2 were discovered to have a protective effect on the risk of scoliosis. Ruminococcaceae UCG009, Catenibacterium, Coprococcus2, Eubacterium (ventriosum group), Lachnospiraceae (FCS020 group), Ruminiclostridium6, and Mollicutes RF9 may increase the occurrence of scoliosis. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results. ConclusionOur study identified four protective bacteria taxa on scoliosis and seven microbiota that may increase scoliosis occurrence. Further MR analysis is required to corroborate our findings, using a more sophisticated technique to obtain estimates with less bias and greater precision or GWAS summary data with more gut microbiome and scoliosis patients.

Characterization of Gut Microbiome Composition in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy.

Patients with triple-negative breast cancer (TNBC) achieving a pathological complete response (pCR) after neoadjuvant chemotherapy have a better event-free survival. The role of gut microbiome in early TNBC is underexplored. Microbiome was analyzed by 16SrRNA sequencing. Twenty-five patients with TNBC treated with neoadjuvant anthracycline/taxane-based chemotherapy were included. Fifty-six percent achieved a pCR. Fecal samples were collected before (t0), at 1 (t1), and 8 weeks (t2) from chemotherapy. Overall, 68/75 samples (90.7%) were suitable for microbiome analysis. At t0, pCR group showed a significantly higher α-diversity as compared with no-pCR, (P = .049). The PERMANOVA test on β-diversity highlighted a significant difference in terms of BMI (P = 0.039). Among patients with available matched samples at t0 and t1, no significant variation in microbiome composition was reported over time. Fecal microbiome analysis in early TNBC is feasible and deserves further investigation in order to unravel its complex correlation with immunity and cancer.

Gut Microbiome Composition in Patients with Chronic Urticaria: A Review of Current Evidence and Data.

Recent studies have linked gut microorganism composition and chronic urticaria (CU); however, the underlying mechanisms responsible for this connection are unknown. Since the human immune system is in homeostasis with microbiota, and the composition of the microbiome regulates the development and function of the immune system, it is likely that an alteration of microbiota components (a dysbiosis) could influence the course of chronic spontaneous urticaria (CSU), including disease severity, patient quality of life and treatment outcome. To date, several studies have identified changes in the gut microbiota composition of patients with CSU, though only a few have exhibited metabolic abnormalities associated with gut dysbiosis. The studies on CSU patients predominantly showed that the relative abundance of beneficial bacteria was decreased (Firmicutes and Bacteroides), while that of opportunistic bacteria was increased (Enterobacteria and Proteobacteria). In addition, serum metabolome analysis revealed that gut microbiota-associated alterations in unsaturated fatty acids and the butanoate metabolism pathway may play a role in CSU. These findings are potentially associated with inflammation mediated by the imbalance of Th1/Th2/Th17 cytokines, which might contribute to CSU pathogenesis. Further research in this field could improve clinical, diagnostic, and therapeutic approaches to patients with CSU. By applying new knowledge on gut microbial communities and metabolomics, future CSU therapies could modify the microbiota composition using agents such as probiotics or other similar agents, which, in combination with current standard therapies, could hopefully lead to a reduction in symptoms and an improved quality of life for CSU patients.

Improving ICI outcomes with a little help from my microbial friends

Gut microbiome composition correlates with responsiveness to immune checkpoint inhibitor therapy. In a recent study in Science, Baruch etal. manipulated gut microbiome composition in patients with refractory metastatic melanoma using fecal microbiota transplants. Fecal microbiota transplant was safe and partially effective in inducing remission in refractory patients.

Physiologic colonic uptake of 18F-FDG on PET/CT is associated with clinical response and gut microbiome composition in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) represent the backbone treatment for advanced non-small cell lung cancer (NSCLC). Emerging data suggest that increased gut microbiome diversity is associated with favorable response to ICI and that antibiotic-induced dysbiosis is associated with deleterious outcomes. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics (ATB) and could act as a surrogate marker for microbiome composition and predict prognosis. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with gut microbiome profiling and clinical outcomes in patients with advanced NSCLC. Seventy-one patients with advanced NSCLC who underwent a PET/CT prior to ICI were identified. Blinded colonic contouring was performed for each colon segment and patients were stratified according to the median of the average colon SUVmax as well as for each segment in low vs. high SUVmax groups. Response rate, progression-free survival (PFS), and overall survival (OS) were compared in the low vs. high SUVmax groups. Gut microbiome composition was analyzed for 23 patients using metagenomics sequencing. The high colon SUVmax group had a higher proportion of non-responders (p = 0.033) and significantly shorter PFS (4.1 vs. 11.3months, HR 1.94, 95% CI 1.11-3.41, p = 0.005). High caecum SUVmax correlated with numerically shorter OS (10.8 vs. 27.6months, HR 1.85, 95% CI 0.97-3.53, p = 0.058). Metagenomics sequencing revealed distinctive microbiome populations in each group. Patients with low caecum SUVmax had higher microbiome diversity (p = 0.046) and were enriched with Bifidobacteriaceae, Lachnospiraceae, and Bacteroidaceae. Lower colon physiologic 18F-FDG uptake on PET/CT prior to ICI initiation was associated with better clinical outcomes and higher gut microbiome diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a potential novel marker of gut microbiome composition and may predict clinical outcomes in this population.

Gut dysbiosis associated with clinical prognosis of patients with primary biliary cholangitis.

Although some relationships between gut microbiota and liver diseases have been reported, it remains uncertain whether changes in gut microbiota owing to differences in race, food and living environment have similar effects. Response to ursodeoxycholic acid (UDCA) may predict the long-term prognosis of patients with primary biliary cholangitis (PBC); however, little is known about the significance of the gut microbiome in patients with PBC. We elucidated the relationships among clinical profiles, biochemical response to UDCA and gut microbiome composition in patients with PBC. Fecal samples from 76 patients with PBC treated at our hospital were collected; patients whose UDCA intake period was <1year were excluded. The microbiome structures of patients were determined using 16S ribosomal RNA gene sequencing and were statistically compared with those of healthy subjects. The structures of patients in the UDCA responder (n = 43) and non-responder (n = 30) groups were compared according to the Nara criteria (reduction rate of gamma-glutamyl transpeptidase, ≥69%, after 1year). Compared with healthy subjects, bacterial diversity was lower in patients with PBC, with a decreased abundance of the order Clostridiales and increased abundance of Lactobacillales. The UDCA non-responder group had a significantly lower population of the genus Faecalibacterium, known as butyrate-producing beneficial bacteria (P < 0.05), although no significant differences in gender, body mass index, medicated drugs or other serological data were indicated between these two groups. Gut dysbiosis with loss of beneficial Clostridiales commensals was observed in patients with PBC. Decrease in Faecalibacterium abundance might predict the long-term prognosis of patients with PBC.

Altered gut microbiome composition in patients with Vogt-Koyanagi-Harada disease

ABSTRACT Background Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder characterized by granulomatous panuveitis. Gut microbiome has been considered to play a role in the pathogenesis of this disease but whether the alternation of gut microbiome was involved is unclear. This study was set up to identify abnormalities of gut microbiome composition in VKH disease. Results Depleted butyrate-producing bacteria, lactate-producing bacteria and methanogens as well as enriched Gram-negative bacteria were identified in the active VKH patients, as well as in VKH patients of Mix enterotype and Bacteroides enterotype. Changes of gut microbiome in the VKH patients were partially restored after an immunosuppressive treatment. The disease susceptibility genotype HLA-DRA was associated with Bacteroides sp.2.1.33B, Paraprevotella clara, Alistipes finegoldii and Eubacterium eligens. A microbial marker profile including 40 disease-associated species was established to differentiate patients from controls. Another microbial marker profile including 37 species was found to be associated with the response to treatment. An animal experiment showed that transfer of gut microbiome from VKH patients could significantly exacerbate disease activity clinically and pathologically in the recipient mice. Conclusion Our results revealed a distinct gut microbiome signature in VKH patients and showed an exacerbating effect of this gut microbiome on experimental autoimmune uveitis (EAU). We also developed two microbial marker profiles in differentiating VKH patients from healthy controls as well as predicting the effectiveness of treatment.

769-P: Short-Term Dietary Reduction of Branched-Chain Amino Acids Reduces Meal-Induced Insulin Secretion and Modifies Microbiome Composition in Overweight Patients with Type 2 Diabetes

Increased levels of branched-chain amino acids (BCAA) associate with insulin resistance and type 2 diabetes (T2D), which could result from dietary habits, gut microbiome composition or direct effects on cellular energy metabolism. We hypothesized that reduced dietary intake of BCAA improves whole body insulin sensitivity and hyperinsulinemia in patients with T2D. In a randomized, placebo-controlled, double-blinded, cross over trial, 12 metabolically well-controlled patients with T2D received an isocaloric diet (protein: 1 g/kg body weight), containing either the complete amino acid set (BCAA+) or a 60% reduction in BCAA (BCAA-) for 1 week each. Effects on glucose homeostasis were assessed from mixed meal tolerance tests (MMT) and hyperinsulinemic-euglycemic clamps (HEC, M-value), and pathways affecting insulin signaling were analyzed in muscle and adipose tissue biopsies. Microbiome composition was assessed by next generation sequencing. After the BCAA- diet, MMT-derived insulin secretion was 28% lower compared to the BCAA+ diet (p&amp;lt;0.05). After the BCAA- diet, MMT-derived insulin sensitivity (PREDIM, the validated predicted HEC-derived M-value from meal data), turned 23% higher (p&amp;lt;0.01), whereas HEC-derived insulin sensitivity (M-value) remained unchanged. Respiratory control ratio was 1.7-fold higher in adipose tissue (p&amp;lt;0.05), but unchanged in skeletal muscle. Mechanistic target of rapamycin (mTOR) was downregulated by 13% in adipose tissue (p&amp;lt;0.05). BCAA- diet was associated with a 40% increase of fecal Bacteroidetes and a 11% decrease of Firmicutes (both p&amp;lt;0.05). In conclusion, a short-term dietary reduction of BCAA decreases insulin secretion, increases postprandial insulin sensitivity, which may relate to adipocyte mitochondrial efficiency and altered gut microbiome composition in patients with T2D. Disclosure Y. Karusheva: None. T. van Gemert: None. K. Strassburger: None. D.F. Markgraf: Research Support; Self; Sanofi. T. Jelenik: None. L. Mastrototaro: None. M. Simon: None. O.P. Zaharia: None. K. Bodis: None. F. Bärenz: None. D. Schmoll: Employee; Self; Sanofi-Aventis Deutschland GmbH. V. Burkart: None. K. Muessig: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. Funding Sanofi Aventis Deutschland GmbH

SLC39A8 missense variant is associated with Crohn's disease but does not have a major impact on gut microbiome composition in healthy subjects

BackgroundGene-microbiome interactions are important in aetiology and pathogenesis of inflammatory bowel disease, a chronic inflammatory disorder of the gastrointestinal tract consisting of Crohn’s disease and ulcerative colitis. Scarce studies on gene-microbiome interactions show very little overlap in their results. Therefore, it is of utmost importance that gene-microbiome studies are repeated. We aimed to replicate the association between the SLC39A8 [Thr]391 risk allele and gut microbiome composition in patients with inflammatory bowel disease and healthy controls.MethodsWe collected faecal samples, peripheral blood and extensive phenotype data from 291 patients with inflammatory bowel disease and 476 healthy controls. Carrier status information was obtained from whole exome sequencing data, generated using the Illumina HiSeq. The gut microbiome composition was determined by tag-sequencing the 16S rRNA gene. Associations between carrier status and disease were tested using the Wilcoxon-Mann-Whitney test. Associations between carriers and gut microbiome composition were determined using principal coordinate analyses, variance explained, alpha diversity and additive general linear models in inflammatory bowel disease, healthy controls and all groups combined.ResultsCrohn’s disease patients were more often carriers of the missense variant (21/171, 12.3%) than controls (30/476, 6.3%) (OR = 2.1, P = 0.01). We could not identify associations between carrier status and overall gut microbiome composition and microbial richness in all tested groups after correcting for potential confounding factors. We did identify 37 different operational taxonomical units to be associated with carrier status among the tested groups. Two of these 37 were identified before in the discovery study.ConclusionsWe could confirm the genetic association of the SLC39A8 [Thr]391 risk allele with Crohn’s disease but we could only limited replicate the association in gut microbiome composition. Independent replication of gene-microbiome studies is warranted to identify true biological mechanisms.

Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis

Complications of end-stage renal disease (ESRD) are critically related to inflammation. The gut microbiome is a key driver of inflammation. Since dialysis modalities may differently influence the gut microbiome, we aimed to compare the effects of haemodialysis (HD) and peritoneal dialysis (PD) on patients’ gut microbiome composition and function. We therefore studied faecal microbiome composition and function as well as inflammation and gut permeability in 30 patients with ESRD (15 HD, 15 PD) and compared to 21 healthy controls. We found an increase in potentially pathogenic species and a decrease in beneficial species in patients on HD and to a lesser extend in patients on PD when compared to controls. These changes in taxonomic composition also resulted in differences in predicted metagenome functions of the faecal microbiome. In HD but not in PD, changes in microbiome composition were associated with an increase in c-reactive protein (CRP) but not with intestinal inflammation or gut permeability. In conclusion microbiome composition in ESRD differs from healthy controls but also between modes of dialysis. These differences are associated with systemic inflammation and cannot completely be explained by dialysis vintage. The mode of renal replacement therapy seems to be an important driver of dysbiosis in ESRD.