Cannabinoid receptor 1 activity promotes microbial dysbiosis by stimulating the oxygen-dependent expansion of Enterobacteriaceae
The endocannabinoid system is comprised of bioactive lipids that signal via cannabinoid receptors, which can modulate barrier and immune functions along the gastrointestinal tract. Clinical studies indicate that endocannabinoid activity is dysregulated in inflammatory bowel diseases. Here, we show that endocannabinoid activity promotes metabolic dysfunction within the colonic mucosa, resulting in…
Research reveals that activation of cannabinoid receptor 1 (CB1) contributes to microbial imbalances in the gut by encouraging the growth of Enterobacteriaceae, a family of bacteria commonly associated with inflammation. This effect is mediated by the endocannabinoid system, which is known to influence barrier and immune functions along the gastrointestinal tract.
Inflammatory bowel diseases often exhibit dysregulation of endocannabinoid activity. The study demonstrates that stimulating CB1 receptors leads to metabolic dysfunction in the colonic mucosa, disrupting the delicate balance of oxygen-dependent pathways that typically keep pathogenic bacteria in check. This results in a shift towards Enterobacteriaceae, a prevalent condition in inflammation-associated dysbiosis.
The study further reveals that CB1 activation triggers a series of changes in the mucosal lining, including transcriptional signatures of mitochondrial stress and immune activation. These changes precede a decline in ATP production and the upregulation of aerobic respiration genes within Escherichia coli residing in the gut. When genetic modifications limit aerobic respiration in E. coli, the bacterium's growth is curtailed, suggesting that CB1 activation promotes oxygen-dependent bacterial proliferation.
In a mouse model susceptible to inflammatory bowel disease, endocannabinoid activity exacerbates infection by an E. coli pathogen, correlating with heightened inflammatory markers. Conversely, in mice resistant to inflammation, a single dose of CB1 stimulation accelerates the infection, exacerbating colitis. Collectively, these findings propose a model where CB1 receptor signaling at the cannabinoid 1 receptor disrupts respiratory metabolism in the colon, undermining the anoxic conditions crucial for maintaining low levels of aerobic pathogens.
The study emphasizes the proinflammatory role of endocannabinoid activity in contributing to intestinal disease development.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
