Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models

Abstract

Background The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies. Results Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10. Conclusions Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites.

Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease

“…• Allowed the retention of a beneficial microbiota that reduced the severity of colitis upon fecal microbiota transplantation in an experimental colitis model (Strati et al, 2021).…”

Gut Microbiota and Parkinson’s Disease: Implications for Faecal Microbiota Transplantation Therapy

“…It modulates the digestion events (such as secretion and motility), immunologic function, and perception or emotional response to visceral stimuli under normal condition ( Mayer et al., 2006 ). Its dysfunction is related to several disorders ( Cryan and O'Mahony, 2011 ; Aziz et al., 2013 ; Bonaz and Bernstein, 2013 ; Davari et al., 2013 ; Felice et al., 2016 ; Grenham et al., 2011 ; Mayer, 2011 ; Parashar and Udayabanu, 2017 ), like depression, anxiety, hepatopathy (Iwaki et al., 2021), intestinal inflammation, GI motility disorder, and chronic abdominal pain syndrome ( Cryan and Dinan, 2012 ; Strati et al., 2021 ). Besides, this axis is linked with stress behaviors and responses ( Clarke et al., 2013 ; O'Mahony et al., 2015 ; Parashar and Udayabanu, 2017 ).…”

In situ treatment of H. pylori infection in mice stomach with bioengineered probiotic bacteria releasing guided Antimicrobial peptides

“…The copyright holder for this preprint this version posted June 11, 2021. ; https://doi.org/10. 1101/2021…”

“…The copyright holder for this preprint this version posted June 11, 2021. ; https://doi.org/10.1101/2021.06.11.448139 doi: bioRxiv preprint into intestinal inflammatory diseases like colitis (Strati et al, 2021), worsens neuro-immune mechanisms and viscerosensory functionalities (Aguilera et al, 2015) and often makes way for bloom of pathogens (Vangay et al, 2015) creating other possibly more serious infectious diseases. This presents a dilemma, as stronger small molecule antibiotics are required to kill bacteria with ever-evolving antibiotic resistance mechanisms, but stronger antibiotics kill a wider variety of commensal bacteria (Becattini et al, 2016;Langdon et al, 2016;Zarrinpar et al, 2018).…”