TY - JOUR
T1 - Antibiotics damage the colonic mucus barrier in a microbiota-independent manner
AU - Sawaed, Jasmin
AU - Zelik, Lilach
AU - Levin, Yehonatan
AU - Feeney, Rachel
AU - Naama, Maria
AU - Gordon, Ateret
AU - Zigdon, Mor
AU - Rubin, Elad
AU - Telpaz, Shahar
AU - Modilevsky, Sonia
AU - Ben-Simon, Shira
AU - Awad, Aya
AU - Harshuk-Shabso, Sarina
AU - Nuriel-Ohayon, Meital
AU - Werbner, Michal
AU - Schroeder, Bjoern O.
AU - Erez, Amir
AU - Bel, Shai
N1 - Publisher Copyright: copyright © 2024 the Authors
PY - 2024/9/13
Y1 - 2024/9/13
N2 - Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.
AB - Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.
UR - http://www.scopus.com/inward/record.url?scp=85204031252&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/sciadv.adp4119
DO - https://doi.org/10.1126/sciadv.adp4119
M3 - مقالة
C2 - 39259805
SN - 2375-2548
VL - 10
JO - Science Advances
JF - Science Advances
IS - 37
M1 - eadp4119
ER -