scholarly journals Sex-related Alterations of Gut Microbiota in the C57BL/6 Mouse Model of Inflammatory Bowel Disease

2019 ◽  
Vol 24 (3) ◽  
pp. 173-182 ◽  
Author(s):  
Hee Jin Son ◽  
Nayoung Kim ◽  
Chin-Hee Song ◽  
Ryoung Hee Nam ◽  
Soo In Choi ◽  
...  
2018 ◽  
Vol 84 (18) ◽  
Author(s):  
Lingyu Yang ◽  
Chao Liu ◽  
Wenjing Zhao ◽  
Chuan He ◽  
Jinmei Ding ◽  
...  

ABSTRACTEstablishing and maintaining beneficial interactions between the host and associated gut microbiota are pivotal requirements for host health. Autophagy is an important catabolic recycling pathway that degrades long-lived proteins and some organelles by lysosome to maintain cellular homeostasis. Although impaired autophagy is thought to be closely correlated with Crohn's disease (CD), the functional role of autophagy in the maintenance of gut microbiota is poorly understood. As autophagy-related 5 (Atg5) is a key gene associated with the extension of the phagophoric membrane in autophagic vesicles, we established a gut-specificAtg5knockout mouse model, and we found that the disruption of autophagic flux in the intenstinal epithelium cells dramatically altered the composition of the gut microbiota and reduced alpha diversity. Microbial function prediction indicated that the pathway allocated for infectious diseases was enriched inAtg5−/−mice. “CandidatusArthromitus” and thePasteurellaceaefamily were increased inAtg5−/−mice, whereasAkkermansia muciniphilaand theLachnospiraceaefamily were reduced. Transcriptome analysis revealed that two key inflammatory bowel disease (IBD)-related transcription factors, RORC and TBX21, of host cells were upregulated inAtg5−/−mice, thus elevating the Muc2-related immunological response. The findings suggest that intestinal autophagy plays a vital role in modulating the diversity and composition of gut microbiota.IMPORTANCEThe homeostasis of host-microbiota interactions is of great importance to host health. Previous studies demonstrated that disruption of autophagy was linked to inflammatory bowel disease. However, the interaction mechanism of gut microbiota regulated by autophagy was obscure. In an intestinal epithelium-specific autophagy-related 5 (Atg5) knockout mouse model, we observed a significant alteration and decreased diversity in the gut microbiota ofAtg5-deficient mice compared with that of wild-type mice. Although the numbers of some organisms (e.g.,Akkermansia muciniphilaand members of theLachnospiraceaefamily) associated with the control of inflammation decreased, those of proinflammationory bacteria (e.g., “CandidatusArthromitus”) and potential pathogens (thePasteurellaceaefamily) increased inAtg5−/−mice. Differential gene expression analysis revealed that two key genes,RORCandTBX21, involved in inflammatory bowel disease were upregulated inAtg5−/−mice. Our study suggests thatAtg5deficiency results in an imbalance of the host-microbe interaction and deterioration of the gut microenvironment.


2020 ◽  
Author(s):  
Lisa Abernathy Close ◽  
Madeline R Barron ◽  
James M George ◽  
Michael G Dieterle ◽  
Kimberly C Vendrov ◽  
...  

Clostridioides difficile has emerged as a noteworthy pathogen in patients with inflammatory bowel disease (IBD). Concurrent IBD and CDI is associated with increased morbidity and mortality compared to CDI alone. IBD is associated with alterations of the gut microbiota, an important mediator of colonization resistance to C. difficile. Here, we describe and utilize a mouse model to explore the role of intestinal inflammation in susceptibility to C. difficile colonization and subsequent disease severity in animals with underlying IBD. Helicobacter hepaticus, a normal member of the mouse gut microbiota, was used to trigger inflammation in the distal intestine akin to human IBD in mice that lack intact IL-10 signaling. Development of IBD resulted in a distinct intestinal microbiota community compared to non-IBD controls. We demonstrate that in this murine model, IBD was sufficient to render mice susceptible to C. difficile colonization. Mice with IBD were persistently colonized by C. difficile, while genetically identical non-IBD controls were resistant to C. difficile colonization. Concomitant IBD and CDI was associated with significantly worse disease than unaccompanied IBD. IL-10-deficient mice maintained gut microbial diversity and colonization resistance to C. difficile in experiments utilizing an isogenic mutant of H. hepaticus that does not trigger intestinal inflammation. These studies in mice demonstrate that the IBD-induced microbiota is sufficient for C. difficile colonization and that this mouse model requires intestinal inflammation for inducing susceptibility to CDI in the absence of other perturbations, such as antibiotic treatment.


2019 ◽  
Author(s):  
Isabel Cornejo-Pareja ◽  
Beatriz Garcia-Munoz ◽  
Eduardo Romero-Perez ◽  
Eduardo Garcia-Fuentes ◽  
S Tapia-Paniagua ◽  
...  

2019 ◽  
Vol 156 (6) ◽  
pp. S-1124
Author(s):  
Clara Caenepeel ◽  
Sara Vieira-Silva ◽  
Jorge F. Vázquez-Castellanos ◽  
Bram Verstockt ◽  
Marc Ferrante ◽  
...  

2017 ◽  
Vol 312 (4) ◽  
pp. G327-G339 ◽  
Author(s):  
Rebecca L. Knoll ◽  
Kristoffer Forslund ◽  
Jens Roat Kultima ◽  
Claudius U. Meyer ◽  
Ulrike Kullmer ◽  
...  

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn’s disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.


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