The present study aimed to determine if
metformin exerts anti-inflammatory and mucus-protective effects via the gut microbiota.
Metformin has extensive benefits including anti-inflammatory effects. Previous studies showed that
metformin changed the gut microbiota composition and increases the number of goblet cells. Intestinal
dysbiosis and goblet cell depletion are important features of
ulcerative colitis (UC). The underlying mechanism and whether
metformin can improve the mucus barrier in UC remain unclear.
Metformin (400 mg/kg/day) was administered to mice with
dextran sulfate sodium (DSS)-induced UC for 2 wk to investigate the effects of
metformin on the intestinal mucus barrier. The gut microbiota was depleted, using
antibiotics, to explore its role in the mucus-protecting effects of
metformin. Akkermansia muciniphila (A. muciniphila), which was enriched in
metformin-treated mice, was administered to mice to investigate the effects of the bacteria on UC and the mucus barrier.
Metformin attenuated DSS-induced UC in mice, as evidenced by the alleviation of
diarrhea,
hematochezia, and the decrease in
body weight. The expression of mucin2, a prominent mucus barrier
protein, was increased in the
metformin-treated group compared to the DSS-treated group. Furthermore, fecal
16S rRNA analysis showed that
metformin treatment changed the gut microbiota composition by increasing the relative abundance of Lactobacillus and Akkermansia species while decreasing Erysipelatoclostridium at the genus level.
Antibiotic treatment partly abolished the anti-inflammatory and mucus-protecting effects of
metformin. Administration of A. muciniphila alleviated the colonic
inflammation and mucus barrier disruption.
Metformin alleviated DSS-induced UC in mice and protected against cell damage via affecting the gut microbiota, thereby providing a new mechanism for the
therapeutic effect of
metformin in patients with UC. This study also provides evidence that A. muciniphila as a probiotic has potential benefits for UC.