Childhood intestinal microbiota exacerbates colitis

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder that causes inflammation of the intestine. Although the exact cause of IBD is unknown, several factors have been identified that lead to the disease. These factors are related to age, immune system, genetics, and environment. One of the key factors behind the development of IBD is abnormal gut microbiota.

study: Early gut microbiota govern susceptibility to colitis via microbially-derived ether lipidsImage credit: Design_Cells / Shutterstock

Background

A healthy gut consists of a rich diversity of obligate anaerobes and low oxygen levels. In contrast, IBD patients showed high levels of reactive oxygen species (ROS) and nitrogen. Intestinal inflammation causes an increase in colonic oxygenation, causing a bacterial population imbalance in both aerobic and anaerobic bacterial populations.

In previous studies, Butyricum fungus and bifidobacteria, and their metabolites influence the colonic environment in IBD. As mentioned above, a gut microbial imbalance is present in his IBD patient, which is associated with increased facultative anaerobes and decreased facultative anaerobes.

Plasmalogens are common forms of ether lipids widely distributed in anaerobic bacteria and animals. These are involved in signaling and protection against her ROS and membrane structures. Although plasmalogen synthase (pls) has been associated with most members of the gut microbiota, information about plasmalogen-producing bacteria in the gut microbiota is lacking.

Plasmalogens have recently been discovered in facultative anaerobic and aerobic bacteria. Bacterial communities of plasmalogen-positive species need to be better characterized (pls [PlsA/R]-positive), to elucidate their function in relation to intestinal inflammatory diseases to identify therapeutic targets.

Ether-linked phospholipids have been found to affect ferroptosis, which is associated with the regulation of intestinal disease. However, few studies have been conducted to understand age-related changes in the gut microbiota from young to mature adulthood that affect gut health.

About research

Recent research journal Studies have investigated the role of microbiota associated with the anaerobic plasmalogen biosynthetic pathway in establishing intestinal homeostasis.In this study, the presence of pls [PlsA/R]-Positive bacterial species and plasmalogens confer valuable intestinal homeostasis early in life.

Fecal samples were obtained from 19 IBD patients and 12 healthy individuals. Both male and female individuals with active ulcerative colitis were recruited. The age of the participants he was between 10 and 30 years old.

For animal studies, a mouse model was used. Mice were exposed to a 12 h light/dark cycle with food and water available ad libitum. Colitis was induced in mice by dextran sulfate sodium (DSS). A group of mice without colitis served as controls.

Investigation result

This study focused primarily on ether lipid producing bacteria because of the unique anaerobic biosynthetic pathways involved in regulating early postnatal gut microbiota changes in colitis. Incidence of colitis was associated with high levels of ROS and reduced anaerobic bacterial counts.

Previous studies have shown that ether lipids such as plasmalogens function as ROS scavenger molecules and endogenous antioxidants to promote ferroptosis. This study determined the association between changes in gut microbial architecture, ferroptosis, and the development of colitis.

Etherlipid-producing anaerobic bacteria found in early stages of IBD patients or mice were characterized. Changes in ether-linked lipids, signaling by commensal intestinal anaerobic bacteria, were observed to increase the risk of ferroptosis and colitis.

Previous studies have demonstrated that antibiotic therapy with neomycin, metronidazole, or ciprofloxacin prevents the development of colitis. A reduction in colonic inflammation was observed in germ-free mice (controls) and mice receiving antibiotic treatment at 18 weeks of age. However, barrier function failure occurred. Nonetheless, exacerbation of colitis was observed when 8-week-old mice were given similar antibiotic treatment. These conflicting observations arose due to age-related intestinal dysbiosis, which induced the pathogenesis of intestinal inflammation.

Notably, the current study documents that early microbiota depletion by antibiotic cocktail treatment exacerbates DSS-induced colitis. In contrast, midlife microbiota depletion led to decreased clinical symptoms of colitis with DSS challenge. This finding is consistent with previous reports showing that microbiological disorders in young puppies increase the risk of subsequent colitis. There can be various reasons for this occurrence. One explanation is the effect of early antibiotic treatment, which causes microbial symbiosis of certain bacteria and their metabolites (e.g., secondary bile acids and short-chain fatty acids) to reduce the cytoprotective properties of colonic epithelial cells.

Based on 16S rRNA sequencing, young mice were shown to contain higher levels of plasmalogen-positive species in the colon compared to mature adult mice. Decreases in colonic plasmalogen-producing bacteria and plasmalogen levels correlated with decreases in dimethylacetal (DMA) derivatives in colonic contents of DSS-induced colitis mice. Decreased fecal plasmalogen levels and decreased ether-bound phospholipid levels were observed in microbiota-depleted mice.

Conclusion

Current research has identified microbes that are essential for a healthy gut microbiome during childhood, which may reduce the risk of colitis later in life. Plasmalogens play an important role in the progression of colitis. They can attenuate the inflammatory response and reverse the increased susceptibility to colitis in mice lacking anaerobic bacteria. In the future, it is necessary to elucidate the mechanisms underlying the plasmalogen-positive microbiota to maintain intestinal health.