scholarly journals Fecal Microbiota Alterations Associated With Clinical and Endoscopic Response to Infliximab Therapy in Crohn’s Disease

2020 ◽  
Vol 26 (11) ◽  
pp. 1636-1647
Author(s):  
Xiaojun Zhuang ◽  
Zhenyi Tian ◽  
Rui Feng ◽  
Manying Li ◽  
Tong Li ◽  
...  

Abstract Background Gut microbiota dysbiosis is associated with the occurrence and development of Crohn disease (CD). Currently, infliximab (IFX) is used more and more to treat CD; however, gut microbiota alterations during IFX therapy are variable and sometimes even contradictory. We longitudinally identified microbial changes during IFX therapy associated with the clinical and endoscopic response to IFX treatment in CD. Methods Fecal-associated microbiota was analyzed using 16S sequencing in 49 patients with active CD who were prospectively recruited at baseline, week 6, and week 30, respectively. Moreover, a model trained on the gut microbiota alterations at week 6 was developed to investigate their potential to predict clinical and endoscopic responses to IFX therapy at weeks 14 and 30. Results Characteristics of fecal microbiota composition in patients with CD after IFX treatment displayed an increased diversity and richness, a significant gain in short-chain fatty acid -producing bacteria, and a loss of pathogenic bacteria. Furthermore, certain functional profiles of Kyoto Encyclopedia of Genes and Genomes pathways were predictably altered during the treatment period. Increased proportions of Lachnospiraceae and Blautia were associated with IFX efficacy; the combined increase of these taxa at week 6 showed 83.4% and 84.2% accuracy in predicting clinical response at weeks 14 and 30, respectively, with a predictive value of 89.1% in predicting endoscopic response at week 30. Conclusions We found that IFX diminished CD-related gut microbial dysbiosis by modifying microbiota composition and function. Specifically, increased Lachnospiraceae and Blautia at week 6 are associated with the clinical and endoscopic response to IFX, providing potentially predictive biomarkers for IFX treatment decision-making.

2020 ◽  
Vol 71 (1) ◽  
pp. 149-161 ◽  
Author(s):  
Ilias Attaye ◽  
Sara-Joan Pinto-Sietsma ◽  
Hilde Herrema ◽  
Max Nieuwdorp

Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been shown to considerably alter gut microbiota composition and function. Moreover, several diet-derived microbial metabolites are able to modulate human metabolism and thereby alter CMD risk. Dietary interventions that affect gut microbiota composition and function are therefore a promising, novel, and cost-efficient method to reduce CMD risk. Studies suggest that fermentable carbohydrates can beneficially alter gut microbiota composition and function, whereas high animal protein and high fat intake negatively impact gut microbiota function and composition. This review focuses on the role of macronutrients (i.e., carbohydrate, protein, and fat) and dietary patterns (e.g., vegetarian/vegan and Mediterranean diet) in gut microbiota composition and function in the context of CMD.


2020 ◽  
Vol 70 (1) ◽  
Author(s):  
Yinlong Cheng ◽  
Yining Li ◽  
Yonghong Xiong ◽  
Yixin Zou ◽  
Siyu Chen ◽  
...  

Abstract Purpose To investigate the effect of liver-specific knockdown of ANGPTL8 on the structure of the gut microbiota. Methods We constructed mice with liver-specific ANGPTL8 knockdown by using an adeno-associated virus serotype 8 (AAV8) system harbouring an ANGPTL8 shRNA. We analysed the structure and function of the gut microbiome through pyrosequencing and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional prediction. Results Compared with controls, ANGPTL8 shRNA reduced the Simpson index and Shannon index (p < 0.01) of the gut microbiota in mice. At the phylum level, the sh-ANGPTL8 group showed a healthier gut microbiota composition than controls (Bacteroidetes: controls 67.52%, sh-ANGPTL8 80.75%; Firmicutes: controls 10.96%, sh-ANGPTL8 8.58%; Proteobacteria: controls 9.29%, sh-ANGPTL8 0.98%; F/B ratio: controls 0.16, sh-ANGPTL8 0.11). PCoA and UPGMA analysis revealed a significant difference in microbiota composition, while KEGG analysis revealed a significant difference in microbiota function between controls and the sh-ANGPTL8 group. Conclusion Our results revealed that inhibition of ANGPTL8 signalling altered the structure of the gut microbiome, which might further affect the metabolism of mice. We have thus identified ANGPTL8 as a novel hepatogenic hormone potentially involving the liver-gut axis and regulating the structure of the gut microbiota.


Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 517 ◽  
Author(s):  
Claudia Burrello ◽  
Maria Rita Giuffrè ◽  
Angeli Dominique Macandog ◽  
Angelica Diaz-Basabe ◽  
Fulvia Milena Cribiù ◽  
...  

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.


2018 ◽  
Vol 20 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Jianfei Zhao ◽  
Xiaoya Zhang ◽  
Hongbin Liu ◽  
Michael A. Brown ◽  
Shiyan Qiao

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kelsea Drall ◽  
Hein Tun ◽  
Meghan B Azad ◽  
David Guttman ◽  
Malcolm Sears ◽  
...  

Abstract Objectives Colonization with Clostridioides difficile occurs in up to half of infants and is predicted by formula feeding. Although this microbe does not appear to pose any immediate risks for infants, its presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting changes in the gut microbiome that may increase opportunity for colonization of pathogenic bacteria. We explored these compositional changes in exclusively breastfed, partially breastfed and exclusively formula fed infants to describe the microbial community and C. difficile colonization in infants with distinct diets. Methods This study includes 1562 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Infants provided a fecal sample at 3–4 months of age (Mean: 3.56, SD: 1.00) which was analyzed using 16S rRNA sequencing and targeted qPCR for C. difficile. Mode of feeding was recorded in a questionnaire at a 3 month follow-up visit. C. difficile colonization was defined as positive detection (CD+) in the fecal sample (reference: not present, CD-). Multivariate association with linear models (MaAslin) was used to determine changes in microbiota composition following arsine-square root transformation of relative abundances and FDR correction. Results The prevalence of C. difficile colonization among all infants was 30.9%. Colonization rates differed among feeding groups: 22.63% of exclusively breastfed infants, 35.96% of partially breastfed infants and 49.63% of exclusively formula fed infants (P < 0.001). Microbes of the genus Bifidobacterium were decreased in CD + exclusively breastfed infants compared to non-carriers of the same diet (q = 0.02). Additionally, Blautia, Coprococcus and Clostridium, of the Lachnospiraceae family, and microbes of the Bacteroidetes phylum were of higher relative abundance (all q < 0.01) in breastfed CD + infants (both partial and exclusive). In exclusively formula fed infants, C. difficile colonization was not significantly associated with microbiota composition. Conclusions C. difficile colonization may have a dysbiotic effect on the gut microbiota composition of breastfed infants, changes which have previously been associated with childhood atopy and obesity. Funding Sources Canadian Institutes of Health Research (CIHR). AllerGen Network of Centres of Excellence (NCE)


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.


2014 ◽  
Vol 307 (10) ◽  
pp. G951-G957 ◽  
Author(s):  
Jasmohan S. Bajaj ◽  
I. Jane Cox ◽  
Naga S. Betrapally ◽  
Douglas M. Heuman ◽  
Mitchell L. Schubert ◽  
...  

Proton pump inhibitors (PPI) have been associated with infectious complications in cirrhosis, but their impact on distal gut microbiota composition and function is unclear. We aimed to evaluate changes in stool microbiota composition and function in patients with cirrhosis and healthy controls after omeprazole therapy. Both 15 compensated cirrhotic patients and 15 age-matched controls underwent serum gastrin measurement, stool microbiota profiling with multitagged pyrosequencing, and urinary metabolic profiling with NMR spectroscopy to assess microbial cometabolites before/after a 14-day course of 40 mg/day omeprazole under constant diet conditions. Results before (pre) and after PPI were compared in both groups, compared with baseline by systems biology techniques. Adherence was >95% without changes in diet or MELD (model for end-stage liver disease) score during the study. Serum gastrin concentrations significantly increased after PPI in cirrhosis (pre 38.3 ± 35.8 vs. 115.6 ± 79.3 pg/ml P < 0.0001) and controls (pre 29.9 ± 14.5 vs. 116.0 ± 74.0 pg/ml, P = 0.001). A significant microbiota change was seen in both controls and cirrhosis after omeprazole (QIIME P < 0.0001). Relative Streptococcaceae abundance, normally abundant in saliva, significantly increased postomeprazole in controls (1 vs. 5%) and cirrhosis (0 vs. 9%) and was correlated with serum gastrin levels ( r = 0.4, P = 0.005). We found significantly reduced hippurate in cirrhosis vs. controls both pre- and postomeprazole and increased lactate in both groups post vs. preomeprazole, whereas dimethylamine (DMA) decreased in cirrhosis only. On correlation network analysis, significant changes in linkages of bacteria with metabolites (hippurate/DMA/lactate) were found postomeprazole, compared with pre-PPI in cirrhosis patients. In conclusion, omeprazole is associated with a microbiota shift and functional change in the distal gut in patients with compensated cirrhosis that could set the stage for bacterial overgrowth.


2021 ◽  
Author(s):  
Noel T. Mueller ◽  
Moira K. Differding ◽  
Mingyu Zhang ◽  
Nisa Maruthar ◽  
Stephen P Juraschek ◽  
...  

<b>Objective:</b> To determine the longer-term effects of metformin and behavioral weight loss on gut microbiota and SCFAs. <p><b>Methods: </b>We conducted a parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n=121) to: 1) metformin (up to 2000mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n=114), 6 months (n=109) and 12 months (n=105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. </p> <p><b>Results: </b>Of the 121 participants, 79% were female, 46% were black, and the mean age was 60y. Only metformin intervention significantly altered microbiota composition. Compared to control, metformin increased <i>E. Coli</i> and <i>Ruminococcus torques</i> and decreased <i>Intestinibacter Bartletti</i> at both 6 and 12 months, and decreased the genus <i>Roseburia (genus)</i>, including <i>R. faecis</i> and <i>R. intestinalis,</i> at 12 months. Effects were similar when comparing metformin to the behavioral weight loss group. Metformin also altered 62 metagenomic functional pathways and increased butyrate, acetate, and valerate at 6 months. Behavioral weight loss vs. control did not significantly alter microbiota composition, but did increase acetate at 6 months. Increases in acetate were associated with decreases in fasting insulin.</p> <p><b>Conclusions:</b> Metformin, but not behavioral weight loss, impacted gut microbiota composition and function at 6 months and 12 months. Both metformin and behavioral weight loss altered 6-month SCFAs, including increasing acetate which correlated with improved insulin sensitivity.</p>


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253133
Author(s):  
Guankui Du ◽  
Hairong Huang ◽  
Qiwei Zhu ◽  
Li Ying

Pet ownership is an essential environmental exposure that might influence the health of the owner. This study’s primary objectives were to explore the effects of cat ownership on the gut microbial diversity and composition of owners. Raw data from the American Gut Project were obtained from the SRA database. A total of 214 Caucasian individuals (111 female) with cats and 214 individuals (111 female) without cats were used in the following analysis. OTU number showed significant alteration in the Cat group and Female_cat group, compared with that of the no cat (NC) group and Female_ NC group, respectively. Compared with the NC group, the microbial phylum Proteobacteria was significantly decreased in the Cat group. The microbial families Alcaligenaceae and Pasteurellaceae were significantly reduced, while Enterobacteriaceae and Pseudomonadaceae were significantly increased in the Cat group. Fifty metabolic pathways were predicted to be significantly changed in the Cat group. Twenty-one and 13 metabolic pathways were predicted to be significantly changed in the female_cat and male_cat groups, respectively. Moreover, the microbial phylum Cyanobacteria was significantly decreased, while the families Alcaligenaceae, Pseudomonadaceae and Enterobacteriaceae were significantly changed in the normal weight cat group. In addition, 41 and 7 metabolic pathways were predicted to be significantly changed in the normal-weight cat and overweight cat groups, respectively. Therefore, this study demonstrated that cat ownership could influence owners’ gut microbiota composition and function, especially in the female group and normal-weight group.


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