Changes In Firmicutes Research Articles

Short-term gut microbiota's shift after laparoscopic Roux-en-Y vs one anastomosis gastric bypass: results of a multicenter randomized control trial.

Roux-en-Y (RYGB) and one anastomosis gastric bypass (OAGB) represent two of the most used bariatric/metabolic surgery (BMS) procedures. Gut microbiota (GM) shift after bypass surgeries, currently understated, may be a possible key driver for the short- and long-term outcomes. Prospective, multicenter study enrolling patients with severe obesity, randomized between OAGB or RYGB. Fecal and blood samples were collected, pre- (T0) and 24months postoperatively (T1). GM was determined by V3-V4 16S rRNA regions sequencing and home-made bioinformatic pipeline based on Qiime2 plugin and R packages. To compare OAGB vs RYGB microbiota profile at T1 and its impact on metabolic and nutritional status. 54 patients completed the study, 27 for each procedure. An overall significant variation was detected in anthropometric and serum nutritional parameters at T1, with a significant, similar decrease in overall microbial alpha and beta diversity observed in both groups. An increase in relative abundances of Actinobacteria and Proteobacteria and a reduction of Bacteroidetes, no significant changes in Firmicutes and Verrucomicrobia, with an increase of the Firmicutes/Bacteroidetes ratio were observed. BMS promotes a dramatic change in GM composition. This is the first multicenter, RCT evaluating the impact of OAGB vs Roux-en-Y bypass on GM profile. The bypass technique per se did not impact differently on GM or other examined metabolic parameters. The emergence of slightly different GM profile postoperatively may be related to clinical conditions or may influence medium or long-term outcomes and as such GM profile may represent a biomarker for bariatric surgery's outcomes.

Temozolomide-Induced Changes in Gut Microbial Composition in a Mouse Model of Brain Glioma.

BackgroundGut microbiota is associated with the progression of brain tumors. However, the alterations in gut microbiota observed during glioma growth and temozolomide (TMZ) therapy remain poorly understood.MethodsC57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered through gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses.ResultsNineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased in the early stage (T1) and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase (T2) and then a subsequent decrease (T3). Similar longitudinal changes in Intestinimonas and Anaerotruncus abundance were observed in TMZ-treated mice, but the decrease of Anaerotruncus at T3 in the TMZ-treated group was less than that in the vehicle-treated group. No significant change in Lactobacillus was observed after TMZ treatment. Additionally, compared to vehicle control, TMZ treatment led to an enrichment in Akkermansia and Bifidobacterium.ConclusionGlioma development and progression altered the composition of gut microbiota. Induction of Akkermansia and Bifidobacterium as well as the prevention of the reduction in Anaerotruncus may contribute to the anti-tumor effect of TMZ. This study helps to reveal the association between levels of specific microbial species in the gut and the anti-tumor effect of TMZ.

Correlation of gut microbiota and neurotransmitters in a rat model of post-traumatic stress disorder

To determine the effect of gut microbiota on a rat model of post-traumatic stress disorder (PTSD) and explore the correlation of gut microbiota with behavior and neurotransmitters. We established a single prolonged stress (SPS) model to examine the pathogenesis of PTSD on rat behavior, gut microbiota, and neurotransmitter levels. Rats were separated into control and model groups, and neurotransmitter levels were measured using enzyme linked immunosorbent assay. Then, 16 S rRNA sequencing was used to compare the gut microbiota between the control and model groups. Compared with those in the control group, freezing time significantly increased, while number of standing upright, crossing frequency, time spent in the central arena, and total distance traveled were significantly reduced in the model group after exposure to SPS (all P < .05). Meanwhile, serotonin, or 5-hydroxytryptamine, levels in the brain in the model group were significantly lower than those the control group ( P = .0332). In addition, changes were observed in the gut microbiota diversity and relative abundances of bacterial phyla, orders, families, and genera in the model group. Especially, changes in Firmicutes, Bacteroidetes, Cyanobacteria, and Proteobacteria levels were most pronounced after SPS exposure. Correlation analysis showed that the strongest positive correlation was found between Bacteroidaceae and 5-HT ( P = .0009). Moreover, RF32 abundance was the most negatively related to 5-HT ( P = .0009), crossing frequency ( P = .0007), and total distance ( P = .0003). Our results suggest that SPS model rats showed differences in behavior, neurotransmitter levels, and gut microbiota with control rats. Moreover, Firmicutes, Bacteroidetes, Cyanobacteria, and Proteobacteria were most relevant to the exhibited fear-like and anxiety-like behaviors and significant serotonin content reduction in SPS model rats.

Delineating effect of corn microRNAs and matrix, ingested as whole food, on gut microbiota in a rodent model.

Dietary microRNAs (miRNAs) are thought to regulate a wide range of biological processes, including the gut microbiota. However, it is difficult to separate specific effect(s) of miRNA from that of the food matrix. This study aims to elucidate the specific effect(s) of dietary corn miRNAs, ingested as a whole food, on the gut microbiota. We developed an autoclave procedure to remove 98% of miRNA from corn. A mouse feeding study was conducted comparing autoclaved corn to nonautoclaved corn and purified corn miRNA. Compared to nonspecific nucleotides and corn devoid of miRNAs, feeding purified corn miRNAs or corn to C57BL/6 mice via gavage or diet supplementation for two weeks lead to a decrease in total bacteria in the cecum. The effect appeared to be due to changes in Firmicutes. Additionally, corn matrix minus miRNA and processing also affected gut bacteria. In silico analysis identified corn miRNAs that aligned to Firmicutes genome sequences lending further support to the interaction between corn miRNAs and this bacterium. These data support interactions between plant food miRNA, as well as matrix, and the gut microbiota exist but complex. However, it provides additional support for mechanism by which bioactive dietary components interact with the gut microbiota.

Effects of UVR exposure on the gut microbiota of mice and humans.

Many alterations to the skin microbiome by exposure to UV radiation (UVR) have been postulated and may contribute to the ability of UVR phototherapy to regulate skin inflammatory diseases. Very recently, an effect of sub-erythemal narrowband UVB radiation (311 nm) on the gut microbiome of healthy individuals was reported. The relative abundance of Firmicutes and Proteobacteria increased in faecal samples of those receiving three exposures to narrowband UVB radiation; the Bacteroidetes phyla were reduced by UVB. In mice chronically exposed to sub-erythemal broadband UVR, similar faecal changes in Firmicutes and Bacteroidetes have been reported. Murine studies have allowed a further dissection of the relative ability of UVR and dietary vitamin D to modulate the gut microbiome by analysis of relative bacterial abundance in mice with similar 25-hydroxy vitamin D levels obtained by UVR exposure or from their diet, respectively. The studies of mice recovering from colitis suggested that dietary vitamin D could stimulate greater faecal abundance of Rikenellaceae, whilst exposure to UVR was necessary for changes to the abundance of Lachnospiraceae and Desulfovibrionaceae. Both human and murine studies report that multiple exposures to sub-erythemal UVR can increase the diversity of the gut microbiome, which in turn may be beneficial to the health of the host.

Altered Gut Microbiota and Compositional Changes in Firmicutes and Proteobacteria in Mexican Undernourished and Obese Children.

Mexico is experiencing an epidemiological and nutritional transition period, and Mexican children are often affected by the double burden of malnutrition, which includes undernutrition (13.6% of children) and obesity (15.3%). The gut microbiome is a complex and metabolically active community of organisms that influences the host phenotype. Although previous studies have shown alterations in the gut microbiota in undernourished children, the affected bacterial communities remain unknown. The present study investigated and compared the bacterial richness and diversity of the fecal microbiota in groups of undernourished (n = 12), obese (n = 12), and normalweight (control) (n = 12) Mexican school-age children. We used next-generation sequencing to analyze the V3–V4 region of the bacterial 16S rRNA gene, and we also investigated whether there were correlations between diet and relevant bacteria. The undernourished and obese groups showed lower bacterial richness and diversity than the normalweight group. Enterotype 1 correlated positively with dietary fat intake in the obese group and with carbohydrate intake in the undernourished group. The results showed that undernourished children had significantly higher levels of bacteria in the Firmicutes phylum and in the Lachnospiraceae family than obese children, while the Proteobacteria phylum was overrepresented in the obese group. The level of Lachnospiraceae correlated negatively with energy consumption and positively with leptin level. This is the first study to examine the gut microbial community structure in undernourished and obese Mexican children living in low-income neighborhoods. Our analysis revealed distinct taxonomic profiles for undernourished and obese children.

Childhood Obesity and Firmicutes/Bacteroidetes Ratio in the Gut Microbiota: A Systematic Review.

The aim of the present study was to undertake a systematic review exploring the relationship between childhood obesity and fecal microorganisms, to answer the following question: "Are Firmicutes and Bacteroidetes a significant risk indicator/factor for obesity in children?" The main search terms were "child" and "obesity" together with "gut microbiota" (PubMed: 2005-2017). The minimal requirements for inclusion were the evaluation of gut microbiota composition and BMI in children between 0 and 13 years of age. Assessed articles were carefully classified according to a predetermined criterion, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were considered. Seven articles were critically appraised and used as a basis for conclusions. Three studies showed a positive association between Bacteroides fragilis and obesity. In addition, a high value of evidence indicated that a decrease in the Bacteroidetes phylum and in Bacteroides/Prevotella groups was related to high BMI. For the Firmicutes phylum, one high-quality study highlighted that it was positively correlated with weight gain. With regard to Firmicutes species, Clostridium leptum, Eubacterium hallii, and Lactobacillus spp. indicated adipose tissue storage, while Clostridium difficile and the Staphylococcus genus were correlated with low BMI. Despite the fact that only one study did not perform real-time polymerase chain reaction to quantify the microorganisms, its results corroborated those of the studies that did. Changes in Firmicutes and Bacteroidetes phyla/species levels might in fact be significant indicators/factors for childhood obesity. However, given the small number of articles appraising these entire phyla and the heterogeneity among the species assessed, further well-designed studies are required to improve the knowledge.

Metabolic adaptation to the aqueous leaf extract of Moringa oleifera Lam.-supplemented diet is related to the modulation of gut microbiota in mice.

The aqueous leaf extract of Moringa oleifera Lam. (LM-A) is reported to have many health beneficial bioactivities and no obvious toxicity, but have mild adverse effects. Little is known about the mechanism of these reported adverse effects. Notably, there has been no report about the influence of LM-A on intestinal microecology. In this study, animal experiments were performed to explore the relationships between metabolic adaptation to an LM-A-supplemented diet and gut microbiota changes. After 8-week feeding with normal chow diet, the body weight of mice entered a stable period, and one of the group received daily doses of 750-mg/kg body weight LM-A by gavage for 4weeks (assigned as LM); the other group received the vehicle (assigned as NCD). The liver weight to body weight ratio was enhanced, and the ceca were enlarged in the LM group compared with the NCD group. LM-A-supplemented-diet mice elicited a uniform metabolic adaptation, including slightly influenced fasting glucose and blood lipid profiles, significantly reduced liver triglycerides content, enhanced serum lipopolysaccharide level, activated inflammatory responses in the intestine and liver, compromised gut barrier function, and broken intestinal homeostasis. Many metabolic changes in mice were significantly correlated with altered specific gut bacteria. Changes in Firmicutes, Eubacterium rectale/Clostridium coccoides group, Faecalibacterium prausnitzii, Akkermansia muciniphila, segmented filamentous bacteria, Enterococcus spp., and Sutterella spp. may play an important role in the process of host metabolic adaptation to LM-A administration. Our research provides an explanation of the adverse effects of LM-A administration on normal adult individuals in the perspective of microecology.

Correlation network analysis reveals relationships between diet-induced changes in human gut microbiota and metabolic health.

Background:Recent evidence suggests that the gut microbiota plays an important role in human metabolism and energy homeostasis and is therefore a relevant factor in the assessment of metabolic health and flexibility. Understanding of these host–microbiome interactions aids the design of nutritional strategies that act via modulation of the microbiota. Nevertheless, relating gut microbiota composition to host health states remains challenging because of the sheer complexity of these ecosystems and the large degrees of interindividual variation in human microbiota composition.Methods:We assessed fecal microbiota composition and host response patterns of metabolic and inflammatory markers in 10 apparently healthy men subjected to a high-fat high-caloric diet (HFHC, 1300 kcal/day extra) for 4 weeks. DNA was isolated from stool and barcoded 16S rRNA gene amplicons were sequenced. Metabolic health parameters, including anthropomorphic and blood parameters, where determined at t=0 and t=4 weeks.Results:A correlation network approach revealed diet-induced changes in Bacteroides levels related to changes in carbohydrate oxidation rates, whereas the change in Firmicutes correlates with changes in fat oxidation. These results were confirmed by multivariate models. We identified correlations between microbial diversity indices and several inflammation-related host parameters that suggest a relation between diet-induced changes in gut microbiota diversity and inflammatory processes.Conclusions:This approach allowed us to identify significant correlations between abundances of microbial taxa and diet-induced shifts in several metabolic health parameters. Constructed correlation networks provide an overview of these relations, revealing groups of correlations that are of particular interest for explaining host health aspects through changes in the gut microbiota.

Changes in human gut flora with age: an Indian familial study

BackgroundThe gut micro flora plays vital role in health status of the host. The majority of microbes residing in the gut have a profound influence on human physiology and nutrition. Different human ethnic groups vary in genetic makeup as well as the environmental conditions they live in. The gut flora changes with genetic makeup and environmental factors and hence it is necessary to understand the composition of gut flora of different ethnic groups. Indian population is different in physiology from western population (YY paradox) and thus the gut flora in Indian population is likely to differ from the extensively studied gut flora in western population. In this study we have investigated the gut flora of two Indian families, each with three individuals belonging to successive generations and living under the same roof.ResultsDenaturation gradient gel electrophoresis analysis showed age-dependant variation in gut microflora amongst the individuals within a family. Different bacterial genera were dominant in the individual of varying age in clone library analysis. Obligate anaerobes isolated from individuals within a family showed age related differences in isolation pattern, with 27% (6 out of 22) of the isolates being potential novel species based on 16S rRNA gene sequence. In qPCR a consistent decrease in Firmicutes number and increase in Bacteroidetes number with increasing age was observed in our subjects, this pattern of change in Firmicutes / Bacteroidetes ratio with age is different than previously reported in European population.ConclusionThere is change in gut flora with age amongst the individuals within a family. The isolation of high percent of novel bacterial species and the pattern of change in Firmicutes /Bacteroidetes ratio with age suggests that the composition of gut flora in Indian individuals may be different than the western population. Thus, further extensive study is needed to define the gut flora in Indian population.

190 Functional Aspects of the Intestinal Microbiome in Inflammatory Bowel Disease

Introduction Inflammatory bowel disease (IBD) is associated with alterations in the interaction between resident microbes and the intestinal immune system. While shifts in microbial populations have been repeatedly shown in studies of the intestinal microbiome from IBD patients, potential confounding factors such as treatment or environmental exposures have not been fully accounted for. Furthermore, the functional implications of these microbial changes have not been determined. Material andMethods The composition of the microbiome from intestinal biopsies and stool samples were analyzed by 16S gene pyrosequencing. Gene and pathway composition were assessed from phylogenetically associated reference genomes. A novel combination of sparse linear modeling and factor analysis was used to associate microbial abundance, genes, metabolic modules, and pathways with disease and with environmental factors such as medications and smoking. Results We analyzed the GI microbiome of 119 patients with Crohn's disease (CD), 74 patients with ulcerative colitis (UC) and 27 healthy subjects (HS). In CD patients, Roseburia and Ruminococcus genus, respectively in the Lachnospiraceae and Ruminococcaceae families in the Firmicutes phylum, were less abundant. In CD patients with ileal involvement (iCD, n=43) specifically, sequences of the Ruminococcaceae family and of the Faecalibacterium genus in particular were reduced compared to other subjects. The only statistically significant feature specific to UC was the overrepresentation of Eggerthella genus (Actinobacteria phylum). Immunosuppressive treatment (azathioprine/6-mercaptopurine or anti-TNF agents) was associated with an increase of Escherichia/Shigella genus (Gammaproteobacteria), whereas mesalamine was associated with a decrease of Gammaproteobacteria. Genes involved in genetic information processing, nucleic acid metabolism and biosynthesis, amino acid metabolism and methane oxidation were significantly less abundant in IBD patients than in HS. Lipid metabolism and catabolism modules were decreased in iCD. Conversely, genes involved in nitrogen and sulfur metabolism, cysteine metabolic process and in some amino acid transport systems (complementing reductions in their metabolism) were overrepresented in IBD. In iCD specifically, genes involved in carbohydrate metabolism, metabolisms of cofactors and vitamins, and virulence factors were more abundant. Conclusion IBD and iCD in particular are associated with a dysbiosis characterized by changes in Firmicutes, Proteobacteria and Actinobacteria phyla. Environmental factors and, importantly, treatments are associated with independent changes in the GI microbiome. These modest perturbations in bacterial composition are in turn associated with major perturbations of GI microbiome function with potential impact on the host.

191 The Immunophenotype of the Colonic Mucosa in Children With IBD in “Deep Remission”: Healed is Distinct From Healthy

Introduction Inflammatory bowel disease (IBD) is associated with alterations in the interaction between resident microbes and the intestinal immune system. While shifts in microbial populations have been repeatedly shown in studies of the intestinal microbiome from IBD patients, potential confounding factors such as treatment or environmental exposures have not been fully accounted for. Furthermore, the functional implications of these microbial changes have not been determined. Material andMethods The composition of the microbiome from intestinal biopsies and stool samples were analyzed by 16S gene pyrosequencing. Gene and pathway composition were assessed from phylogenetically associated reference genomes. A novel combination of sparse linear modeling and factor analysis was used to associate microbial abundance, genes, metabolic modules, and pathways with disease and with environmental factors such as medications and smoking. Results We analyzed the GI microbiome of 119 patients with Crohn's disease (CD), 74 patients with ulcerative colitis (UC) and 27 healthy subjects (HS). In CD patients, Roseburia and Ruminococcus genus, respectively in the Lachnospiraceae and Ruminococcaceae families in the Firmicutes phylum, were less abundant. In CD patients with ileal involvement (iCD, n=43) specifically, sequences of the Ruminococcaceae family and of the Faecalibacterium genus in particular were reduced compared to other subjects. The only statistically significant feature specific to UC was the overrepresentation of Eggerthella genus (Actinobacteria phylum). Immunosuppressive treatment (azathioprine/6-mercaptopurine or anti-TNF agents) was associated with an increase of Escherichia/Shigella genus (Gammaproteobacteria), whereas mesalamine was associated with a decrease of Gammaproteobacteria. Genes involved in genetic information processing, nucleic acid metabolism and biosynthesis, amino acid metabolism and methane oxidation were significantly less abundant in IBD patients than in HS. Lipid metabolism and catabolism modules were decreased in iCD. Conversely, genes involved in nitrogen and sulfur metabolism, cysteine metabolic process and in some amino acid transport systems (complementing reductions in their metabolism) were overrepresented in IBD. In iCD specifically, genes involved in carbohydrate metabolism, metabolisms of cofactors and vitamins, and virulence factors were more abundant. Conclusion IBD and iCD in particular are associated with a dysbiosis characterized by changes in Firmicutes, Proteobacteria and Actinobacteria phyla. Environmental factors and, importantly, treatments are associated with independent changes in the GI microbiome. These modest perturbations in bacterial composition are in turn associated with major perturbations of GI microbiome function with potential impact on the host.