Alpha Diversity Of Gut Microbiota Research Articles

Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling

The vagus nerve can transmit signals to the brain resulting in a reduction in depressive behavior as evidenced by the long-term beneficial effects of electrical stimulation of the vagus in patients with intractable depression. The vagus is the major neural connection between gut and brain, and we have previously shown that ingestion of beneficial bacteria modulates behaviour and brain neurochemistry via this pathway. Given the high levels of serotonin in the gut, we considered if gut-brain signaling, and specifically the vagal pathway, might contribute to the therapeutic effect of oral selective serotonin reuptake inhibitors (SSRI). Mesenteric nerve recordings were conducted in mice after treatment with SSRI to ascertain if this class of drugs resulted in increased vagal excitability. Patch clamp recordings of enteric neurons were carried out to measure activity of primary afferent neurons in the gut in response to SSRI and to assess the importance of gut epithelium in transducing signal. The tail suspension test (TST) was used following 14d feeding of SSRI in vagotomised and surgical sham mice to measure depressive-like behaviour. Brain mRNA expression was examined via PCR and the intestinal microbiome was assessed. Mesenteric nerve recordings in BALB/c mice demonstrated that oral treatment with SSRI leads to a significant increase in vagal activity. This effect was not observed in mice treated with a representative noradrenaline-dopamine reuptake inhibitor. It is known that signals from the gut can be transmitted to the vagus via the enteric nervous system. Exposure of the gut to SSRI increased the excitability of intrinsic primary afferent neurons in the myenteric plexus, through an intestinal epithelium dependent mechanism, and alpha-diversity of gut microbiota was altered. Critically, blocking vagal signaling from gut to brain, via subdiaphragmatic vagotomy, abolished the antidepressive effects of oral SSRI treatment as determined by the tail suspension test. This work suggests that vagus nerve dependent gut-brain signaling contributes to the effects of oral SSRI and further, highlights the potential for pharmacological approaches to treatment of mood disorders that focus on vagal stimulation and may not even require therapeutic agents to enter the circulation.

A decreased abundance of clostridia characterizes the gut microbiota in eosinophilic esophagitis.

Abnormalities in the gut microbiome are associated with suppressed Th2 response (Belizario et al., 2018 Mediators Inflamm. 2018:2037838) and predisposition to atopic disease such as asthma and eczema. We investigated if this applies to eosinophilic esophagitis (EoE). Stool bacterial DNA was extracted and followed by 16S rRNA amplification from 12 patients with eosinophilic esophagitis and 12 controls. Alpha‐ and beta‐diversity were analyzed. Only two patients had asthma or atopy and one patient was on budesonide. No patients were on PPIs. Patients with EoE had lower gut microbiota alpha diversity (species richness, P = 0.09; Shannon index, P = 0.01). The microbial composition was distinct as evidenced by significantly different beta diversity (P = 0.03) when compared to healthy controls. There were also significant differences in relative abundance at multiple taxonomic levels when comparing the two communities; at the phylum level, we observed a marked decrease in Firmicutes and increase in Bacteroidetes and at the order and family level there were significant decreases in Clostridia and Clostridiales in patients with EoE (q ≤ 0.1). We conclude that there are significant differences in microbial community structure, microbial richness, and evenness and a significant decrease in taxa within the Clostridia in patients with EoE. Our data suggest that Clostridia based interventions could be tested as adjuncts to current therapeutic strategies in EoE.

Abstract 2830: Breast cancer and the human oral and gut microbiomes

Abstract The human body harbors ten times more bacterial cells than human cells - a stunning figure that suggests a likely dynamic between our bodies and the bacteria we carry, both in health and disease. In this study, we characterized and compared the gut and oral microbiota from women with invasive breast cancer, women with ductal carcinoma in situ (DCIS), and healthy women. Samples were collected prior to any systemic therapy to avoid therapy-associated effects on the microbiomes studied. Kits for collecting oral and stool swab samples were distributed to patients for self-collection. DNA was isolated from these samples and bacterial 16S rRNA was PCR amplified and sequenced. Based on the sequencing results, bacterial taxa present in the samples were enumerated. The gut microbiota of women with breast cancer demonstrated significantly lower alpha-diversity compared to the gut microbiomes of healthy women. In contrast, there was no difference in gut microbiota alpha-diversity of women with DCIS compared to healthy women. There were no differences in alpha-diversity of the oral microbiota between any of the cohorts. Discriminant analysis of principal components (DAPC) at the genus level of both the gut and oral microbiota demonstrated distinct clustering of the DCIS, breast cancer, and healthy cohorts. LEfSe analyses were performed to detect differences in relative abundance of bacterial taxa across the gut and oral samples. The genus Bacteroides was significantly enriched in breast cancer compared to healthy samples, as were the related taxa Bacteroidetes (phylum), Bacteroidia (class), Bacteroidales (order), and Bacteroidaceae (family). The genera Fusicatenibacter and Butyrivibrio, both from the phylum Firmicutes, class Clostridia, order Clostridiales, family Lachnospiraceae, were more abundant in the healthy cohort. Only 2 genera, Fusicatenibacter and Clostridium were differentially abundant between the DCIS and healthy gut samples, both being enriched in the healthy samples. Numerous taxa in the oral microbiota were found to be differentially abundant between cohorts. In particular, 7 genera (Bacteroides, Blautia, Faecalibacterium, Roseburia, Pseudobutyrivibrio, Anaerostipes, and Subdoligranulum) were all significantly enriched in the healthy oral samples compared to the DCIS and breast cancer oral samples. To determine whether the taxonomic differences we observed between the cohorts’ gut and oral microbiota corresponded to functional differences, we performed a predictive functional analysis using Piphillin which identified 35 KEGG pathways differentially present in the gut microbiota and 8 pathways differentially present in the oral samples. Understanding how gut and oral microbiomes relate to breast cancer may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment. Citation Format: Michael J. Campbell, Emma McCune, Breanna Johnson, Tess O'Meara, Diane Heditsian, Susie Brain, Laura Esserman. Breast cancer and the human oral and gut microbiomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2830.

Modulation of fat metabolism and gut microbiota by resveratrol on high-fat diet-induced obese mice.

PurposeThe antioxidant resveratrol (RSV) has low bioavailability and can reach the colon to access the gut microbial ecosystem. RSV administration together with high-fat diet prevented abnormal changes of intestinal microbiota. However, whether or not RSV can reshape the intestinal microbiota of obese mice and alleviate obesity-related diseases remains to be studied. This study aimed to explore the role of RSV in alleviating high-fat-induced obesity and its relationship with oxidative stress and gut microbiota.MethodsMale C57BL/6 mice were divided into five groups and administered for 16 weeks with: standard diet (CON), high-fat diet (60% energy for lard, HFD), and HFD with low, medium, and high dose of RSV, 50, 75, and 100 mg/kg body weight administered daily via drinking water, respectively.ResultsMedium and high RSV treatment significantly prevented body weight gain, decreased relative weight of liver and adipose tissue compared with HFD (P<0.05). All doses significantly prevented HFD-induced increase of serum triglyceride, low density lipoprotein cholesterol, glucose, and endotoxemia (P<0.05). Medium and high dose also prevented chronic inflammation by decreasing serum interleukin-1 and tumor necrosis factor-alpha (P<0.05), and oxidative stress in liver and brain indicated by increase in superoxide dismutase, catalase, glutathione peroxidase activity (P<0.05). Formation of malondialdehyde was prevented by all doses compared with HFD (P<0.05). Both medium and high doses of RES increased alpha diversity of gut microbiota according to the Chao1 and Shannon indices (P<0.05). Medium dose induced obvious shift in gut microbiota composition according to principal component analysis. High dose of RSV effectively prevented HFD-induced increase of Coriobacteriaceae and Desulfovi-brionaceae (P<0.05), which show a significant correlation with body weight (r>0.8 P<0.00).ConclusionRSV prevented HFD-induced endotoxemia, oxidative stress, and gut microbiota change.

Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis.

The cure of hepatitis C virus (HCV) infection may contribute to the reduction of liver fibrosis progression and potentially influence the gut-liver axis. To investigate the influence of HCV infection eradication with direct-acting antivirals (DAAs) on the gut microbiota composition as well as on intestinal and systemic inflammatory parameters in patients with cirrhosis. Consecutive patients with HCV-related cirrhosis receiving DAA treatment were included. The gut microbiota composition, intestinal permeability, and inflammation were assessed before treatment and after 1year. Clinical outcomes such as episodes of decompensation and markers of liver fibrosis were evaluated over a 2-year follow-up period. The gut microbiota alpha diversity in cirrhotic patients, which was lower than that in healthy subjects, was significantly improved by the cure of HCV infection and a shift in the overall gut microbiota composition was observed compared to baseline. The abundance of potentially pathogenic bacteria (Enterobacteriaceae, Enterococcus, and Staphylococcus) was decreased after treatment. The gut microbiota composition was associated with the inflammatory profile and markers of liver fibrosis. Although a significant reduction in the serum levels of cytokines and chemokines was observed post-DAA treatment, measures of intestinal permeability and inflammation remained unchanged. Cure of HCV infection with DAAs in patients with cirrhosis is associated with a modification of the gut microbiota, which correlates with fibrosis and inflammation but does not improve intestinal barrier function.

Gut microbiota in adolescents and the association with fatty liver: the EPOCH study.

BackgroundRecent evidence supports that the gut microbiota may be involved in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and may also offer avenues for treatment or prevention.MethodsWe investigated the associations among gut microbiota, diet and hepatic fat fraction (HFF) in 107 adolescents. Magnetic Resonance Imaging (MRI) was used to assess HFF, and 16S rRNA gene sequencing was performed on collected fecal samples. Dietary intake was assessed using Food Frequency Questionnaires. We examined the association between gut microbiota alpha diversity and HFF, and assessed the predictive accuracy for HFF of 1) taxonomic composition, 2) dietary intake, 3) demographic and comorbid conditions, and 4) the combination of these.ResultsLower alpha diversity was associated with higher HFF (β=−0.19, 95% CI −0.36, −0.02). Selected taxa explained 17.7% (95% CI: 16.0–19.4%) of the variation in HFF. The combination of 2 of these taxa, Bilophila and Paraprevotella, with dietary intake of monounsaturated fatty acids and BMI z-scores explained 32.0% (95% CI: 30.3–33.6%) of the variation in HFF.ConclusionsThe gut microbiota is associated with HFF in adolescents and may be useful to help identify youth who would be amenable to gut microbiota-based interventions.

The Influence of Habitual Food Intake on Fecal Microbiota in Mexican School‐Age Children

BackgroundDiet has been considered as a major modifiable factor influencing gut microbiota composition and function. However this knowledge arises mainly from intervention studies in humans and animal models, where drastic changes in diet are made. In addition, it is important to study the diet not only at nutrient level but through food groups that comprise it, since it takes into account the food integrity. Yet there is insufficient evidence from observational studies addressing how consumption of certain food groups can influence gut microbiota composition, specifically in children of developing countries like Mexico. Therefore, the aim of this study was to evaluate the influence of food intake on the gut microbiota composition in Mexican school‐age children.MethodsThis study was a cross‐sectional study and included 382 children of Mexico City, between 5 and 12 years old (9.68; DE ± 1.8). Habitual dietary intake was assessed through a previously validated semi quantitative Food Frequency Questionnaire of 107 food items that were classified into 17 groups. Analysis of the fecal microbiota was performed through 16S rRNA sequencing, in the Illumina MiSeq platform. Association of fecal microbiota composition with food intake was performed using non‐parametric statistics. The study was performed in accordance with the Basic Principles of the Declaration of Helsinki.ResultsIn this study the intake of certain food groups; fruit, vegetables and legumes showed a positive correlation with the gut microbiota alpha diversity (Shannon index), after adjusting for age and sex (p &lt; 0.05). Higher intake of vegetables, legumes and yogurt further correlated at phyla level with higher relative abundance of Firmicutes (p &lt; 0.05). Yogurt also positively correlated with Actinobacteria relative abundance, specifically to higher abundance of Bifidobacterium. This is in accordance with other trials where yogurt intake has shown to increase Bifidobacteria number. Vegetable intake positively correlated with abundance of Lachnospiraceae, while higher consumption of legumes with increased abundance of Ruminococcaceae and Erysipelothrichaceae. The effect seen in Ruminococcaceae could be influenced by the fiber content of legumes.ConclusionThis study demonstrates that the consumption of vegetables, legumes, and yogurt was related to fecal microbiota composition. To our knowledge this is the first study in Mexican children evaluating the association of food groups with fecal microbiota composition. However it is necessary to continue the research to evaluate the effect of these associations with the metabolic phenotype.Support or Funding InformationThis work was supported by CONACYT grant 248765 to SM‐R