Antibiotic Treatment Induces Long-lasting Changes in the Fecal Microbiota that Protect Against Colitis

Abstract

Background The interplay between host genetics, immunity, and microbiota is central to the pathogenesis of inflammatory bowel disease (IBD). Previous population-based studies suggested a link between antibiotic use and increased IBD risk, but the mechanisms are unknown. The purpose of this study was to determine the long-term effects of antibiotic administration on microbiota composition, innate immunity, and susceptibility to colitis, as well as the mechanism by which antibiotics alter host colitogenicity. Methods Wild-type mice were given broad-spectrum antibiotics or no antibiotics for two weeks, and subsequent immunophenotyping and 16S rRNA gene sequencing-based analysis of the fecal microbiome were performed six weeks later. In a separate experiment, control and antibiotic-treated mice were given seven days of DSS, six weeks after completing antibiotic treatment, and the severity of colitis scored histologically. Fecal transfer was performed from control or antibiotic-treated mice to recipient mice whose endogenous microbiota had been cleared with antibiotics, and the susceptibility of the recipients to DSS-induced colitis was analyzed. Naïve CD4+ T cells were transferred from control and antibiotic-treated mice to immunodeficient Rag-1-/- recipients and the severity of colitis compared. Results Antibiotics led to sustained dysbiosis and changes in T-cell subpopulations, including reductions in colonic lamina propria total T cells and CD4+ T cells. Antibiotics conferred protection against DSS colitis, and this effect was transferable by fecal transplant but not by naïve T cells. Conclusions Antibiotic exposure protects against colitis, and this effect is transferable with fecal microbiota from antibiotic-treated mice, supporting a protective effect of the microbial community.

Enterobacter Ludwigii Protects Experimental Colitis Through CD103+DC and Treg Cells

“…The colitis severity was evaluated through body weight loss, disease activity index (DAI) scores, colon lengths and histopathological scores. ABX treatment, which is widely used to clear normal intestinal bacteria, greatly reduced mice susceptibility to DSS treatment as reported previously [21] (Fig. S2A to D, additional le 2).…”

Postnatal Administration of Lactobacillus rhamnosus HN001 Ameliorates Perinatal Broad‐Spectrum Antibiotic‐Induced Reduction in Myelopoiesis and T Cell Activation in Mouse Pups

“…This may indicate that the effect of lowering or increasing the microbial burden in the gut influences the production of granulocytes in the BM as well as their recruitment into circulation. This is supported by the finding that neonatal mice born to ABX‐treated dams exhibit reduced granulocyte numbers in BM and blood and reduced GMPs in BM . In a previous study, we found that recolonizing germ‐free adult mice with a complete SPF microbiota fully restored mature circulating monocytes and neutrophils, while colonization with a single strain ( L. acidophilus or E. coli ) was not able to do so, probably due to inadequate number and stimulation .…”

“…A comparable reduction in granulocytes/neutrophils is found in BM and circulation in germ‐free neonatal mice and in pups born to antibiotic‐treated dams . Furthermore, ABX treatment of adult mice decreases the number of circulating T cells, and ceasing the treatment gradually restores CD4 + and CD8 + T cells numbers . This gradual lymphocyte restoration coincides with an altered and less diverse microbiota many weeks after the cessation of ABX treatment .…”

Neuro-Immune Networks in Gastrointestinal Disorders

“…Antibiotic pretreated mice were shown to attenuate intestinal chemically induced inflammation [73, 74]. In patients with IBD, a Helicobacter , Campylobacter , and Enterococcus species-dominant microbial profile was reported [75, 76].…”