Differential Susceptibility to T Cell-Induced Colitis in Mice: Role of the Intestinal Microbiota

Abstract

One of the best characterized mouse models of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) is the CD4+CD45RBhigh T cell transfer model of chronic colitis. Following our relocation to Texas Tech University Health Sciences Center (TTUHSC), we observed a dramatic reduction in the incidence of moderate-to-severe colitis from a 16-year historical average of 90% at Louisiana State University Health Sciences Center (LSUHSC) to <30% at TTUHSC. We hypothesized that differences in the commensal microbiota at the 2 institutions may account for the differences in susceptibility to T cell-induced colitis. Using bioinformatic analyses of 16S rRNA amplicon sequence data, we quantified and compared the major microbial populations in feces from healthy and colitic mice housed at the 2 institutions. We found that the bacterial composition differed greatly between mice housed at LSUHSC vs TTUHSC. We identified several genera strongly associated with, and signficantly overrepresented in high responding RAG-/- mice housed at LSUHSC. In addition, we found that colonization of healthy TTUHSC RAG-/- mice with feces obtained from healthy or colitic RAG-/- mice housed at LSUHSC transferred susceptibility to T cell-induced colitis such that the recipients developed chronic colitis with incidence and severity similar to mice generated at LSUHSC. Finally, we found that the treatment of mice with preexisting colitis with antibiotics remarkably attenuated disease. Taken together, our data demonstrate that specific microbial communities determine disease susceptibility and that manipulation of the intestinal microbiota alters the induction and/or perpetuation of chronic colitis.

Prebiotics Regulation of Intestinal Microbiota Attenuates Cognitive Dysfunction Induced by Surgery Stimulation in APP/PS1 Mice

“…Reduced Faecalibaculum has been found in Parkinson’s disease [ 33 ]. The decrease of Muribaculum has been found in the studies of ileitis and T cell-induced colitis [ 34 , 35 ]. Similar to the present results, there is no evidence for the change of Lactobacillus in AD and Parkinson’s disease, although it is beneficial in neurodegenerative diseases [ 36 - 38 ] and could reduce intestinal dysfunction in gluten-specific related immune responses [ 39 ].…”

Vasoactive Intestinal Peptide Deficiency Is Associated With Altered Gut Microbiota Communities in Male and Female C57BL/6 Mice

“…Our present study clearly reveals substantial changes in the gut bacterial ecology that when combined with environmental factors could shift the balance between inflammation versus tolerance helping to explain the vastly different results observed in the VIP IBD literature. Indeed, significant changes in gut microbiota structure have been demonstrated due to different geographical locations of mouse vivariums (Reinoso Webb et al, 2018). These data emphasize the importance for researchers to declare environmental conditions, including mouse chow, bedding, and cage aeration specifics (Ericsson et al, 2018).…”

Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties

“…Thus, inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs are novel and promising targets in countering affective disorders [40]. In addition, as suggested earlier, manipulation of gut microbiome may also be a novel approach in combatting inflammatory disorders including colitis [80–82]. Therefore, further investigation of the role of specific microbiomes in inflammatory processes and interaction of effective anti-inflammatory compounds with this system can not only enhance our understanding of the gut-brain axis, but can also lead to novel intervention in inflammatory diseases.…”