Repeated antibiotic usage independent of recent consumption results in gut barrier dysfunction

Recent evidence suggests that repeated antibiotic usage independent from recent consumption lowers microbial diversity and changes the gut microbiota community for a long period. However, the physiological effects of these changes are largely unknown. We aimed to explore the effect of repeated antibiotic use history on gut microbiota-derived mucus function. We used stool samples from otherwise healthy participants in the Estonian Microbiome cohort who had repeatedly, but not recently, taken antibiotics (5 times in 5 years, but none in the last 6 months) and matched controls with no 10-year antibiotic usage history. The microbiota of these participants were transferred to antibiotic-treated wild-type mice via faecal microbiota transplantation (FMT). Mucus functionality was measured using ex vivo techniques. Microbial community structure and function were assessed using shotgun metagenomics sequencing and LC-MS metabolomics. Mice receiving FMT from the participants repeatedly using antibiotics had reduced mucus growth rate and increased mucus penetrability compared to healthy controls which is associated with a changed microbial community, wherein known mucus-utilizing bacteria (e.g. Akkermansia muciniphila and Bacteroides fragilis) are dominant in the gut. We show that gut microbiota from humans who had repeatedly taken antibiotics resulted in a reduced capacity to prevent antibiotic-mediated mucus defects in mice.