From influencing the social symptoms of autism spectrum disorder to brain development and function, the microbial players in our gut have a complex dialogue with our brains.
We're all familiar with the toll psychological stress takes on the gut – gastrointestinal pain and dysfunction. Stress can also lead to the relapse of gut disorders like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Yet, the mystery persists: why does stress wield such influence over the gut-brain axis? A recent Cell Metabolism study might have unraveled the chain of events triggering stress-induced gut dysfunction.
The Complex Gut System:
The gut relays metabolic, immune, and microbial information to the brain. At the same time, the central nervous system influences the gut through hormone signals to impact gut motility, the immune function of mucus membranes, and even the ecology of the gut microbiome. This last part can cause stress-related stomach churning.
The intestine has various cell types, including the intestinal stem cells (ISC), that play a pivotal role in maintaining gut health. During a process called commitment, ISCs will create new epithelial cells that commit to becoming different types of intestinal epithelial cells. One ISC destiny is to become an intestinal secretory cell that produces hormones, protective mucus, and antimicrobial peptides.
Hailing from China Pharmaceutical University, Nanjing, researchers Wei et al. discovered how psychological stress undermines the commitment process.
Microbial Response to Host Stress:
Under stress, the sympathetic nervous system goes into overdrive, releasing stress hormones. Wei et al. observed that restraint stress in mice triggered an enriched population of Lactobacillus murinus microbes in the gut. With more Lactobacillus murinus came more of a metabolite it produces called indole-3-acetate (IAA). Unfortunately, IAA disrupts mitochondrial respiration in ISCs and specifically impairs the secretory cell lineage commitment.
Remarkably, when testing human fecal material, the researchers correlated high concentrations of IAA with gut dysfunction.
Hope for Gut Woes:
For those grappling with poorly managed disorders like IBS and IBD, Wei et al.'s study offers a beacon of hope. Oral alpha-ketoglutarate supplementation emerged as a potential remedy. Wei et al. demonstrated that this treatment bolstered ISC differentiation, conferring resilience to stress-triggered intestinal epithelial injury.
The newfound understanding of the stress-induced microbial pathway presents a therapeutic target, potentially alleviating the double whammy of stress and gut dysfunction.
Sources: Cell Metabolism, Current Gastroenterology Reports, Experimental Cell Research
