Nuriel-Ohayon, M. | Search bioRxiv

bioRxiv2022

Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress

Colonic goblet cells are specialized epithelial cells that secrete mucus to form a barrier between the host and its microbiota, thus preventing bacterial invasion and inflammation. How goblet cells control the amount of mucus they secrete is unclear. We found that constitutive activation of autophagy in mice via Beclin 1 led to production of a thicker and less penetrable mucus layer by reducing endoplasmic reticulum (ER) stress. Accordingly, inhibiting Beclin 1-induced autophagy via Bcl-2 impaired mucus secretion. Furthermore, alleviating intestinal ER stress with a bile acid, or activating the unfolded protein response (UPR) pharmacologically via eIF2 phosphorylation, led to excessive mucus production. Over-production of mucus altered the gut microbiome, with expansion of mucus-utilizing bacteria, and protected from intestinal inflammation. Thus, ER stress is a cell-intrinsic switch that limits mucus secretion, while autophagy maintains proper mucus secretion and intestinal homeostasis by relieving ER stress.

immunology↗

bioRxiv2021

Progesterone supplementation in mice leads to microbiome alterations and weight gain in a sex-specific manner

BackgroundProgesterone is a steroid hormone produced by the ovaries, involved in pregnancy progression and necessary for successful gestation. We have previously shown that progesterone affects gut microbiota composition and leads to increased relative abundance of Bifidobacterium. ResultsIn non-pregnant female GF mice, levels of progesterone were significantly higher than in SPF mice of the same status. However, no significant differences were observed between GF and SPF males. Females treated with progesterone gained more weight than females treated with a placebo. In contrast to female mice, males treated with progesterone did not gain significantly more weight than males treated with a placebo. Progesterone supplementation led to microbial changes in females but not in males (16S rRNA sequencing). Accordingly, the weight gain observed in female mice treated with progesterone was fully transferable to both male and female germ-free mice via fecal transplantation. ConclusionsWe demonstrate that bacteria play a role in regulating progesterone levels in a female-specific manner. Furthermore, weight gain and metabolic changes associated with progesterone may be mediated by the gut microbiota.

microbiology↗