Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder that causes intestinal inflammation. Although the precise reason for IBD is unknown, several aspects that result in this disease have been identified. These aspects are linked to age, immune system, genetics, and environment. One among the important thing aspects behind IBD manifestation is gut microbial dysbiosis.

Study: Early-Life Gut Microbiota Governs Susceptibility to Colitis via Microbial-Derived Ether Lipids. Image Credit: Design_Cells / Shutterstock

Background

A healthy gut comprises a wealthy diversity of obligate anaerobes and low oxygen levels. In contrast, individuals with IBD exhibited a high level of reactive oxygen species (ROS) and nitrogen. Intestinal inflammation triggers a rise in colonic oxygenation, which ends up in bacterial population imbalance in each aerobic and anaerobic bacteria populations.

Prior research has shown how obligate anaerobes, similar to Clostridium butyricum and Bifidobacterium, and their metabolites affect the colonic environment in IBD. As stated above, gut microbial imbalance is present in IBD patients, which has been related to increased facultative anaerobes and decreased facultative anaerobes. 

Plasmalogens are a standard type of ether lipids widely distributed in anaerobic bacteria and animals. These are involved with signaling and protection against ROS and membrane structure. Regardless that plasmalogen synthase (pls) has been linked to the vast majority of the members of the gut microbiome, there was a dearth of data regarding plasmalogen-producing bacteria in gut microbiota. 

Recently, plasmalogens have been present in facultative anaerobic and aerobic bacteria. There may be a necessity to raised characterize bacterial communities of plasmalogen-positive species (pls [PlsA/R]-positive) and elucidate their function linked to gut inflammatory diseases to discover therapeutic targets. 

Ether-linked phospholipids have been found to influence ferroptosis, which is related to the regulation of intestinal diseases. Nonetheless, few studies have been conducted to know the age-related changes within the gut microbiome, i.e., from young maturity to the mature adult stage, which influences intestinal health. 

Concerning the Study

A recent Research journal study investigated the role of microbiota linked to the anaerobic plasmalogen biosynthetic pathway in establishing intestinal homeostasis. The study hypothesized that the presence of pls [PlsA/R]-positive bacterial species and plasmalogen bestow useful intestine homeostasis in formative years. 

Feces samples from nineteen IBD patients and twelve healthy individuals were obtained. Each female and male individuals who had energetic ulcerative colitis were recruited. The age of the participants was between 10 and 30 years.

For animal experiments, mice models were used. The mice were subjected to 12 hours of sunshine/dark cycle with free access to food and water. Colitis was induced in mice by dextran sulfate sodium (DSS). A bunch of mice without colitis was regarded as a control.

Study Findings

The study predominantly focussed on bacteria-producing ether lipids due to their unique anaerobic biosynthesis pathways related to the regulation of early-life gut microbiota alteration on colitis. The incidence of colitis was related to high levels of ROS and decreased anaerobic bacteria population.

Prior studies have indicated that ether lipids, similar to plasmalogens, function as ROS scavenger molecules and endogenous antioxidants to advertise ferroptosis. The current study determined the association between changes in gut microbial structure, ferroptosis, and colitis development.

Ether lipids-producing anaerobic bacteria, present in the early stages of lifetime of patients or mice with IBD, were characterised. It was observed that changes in ether-linked lipids, signaling on account of gut anaerobic bacterial dysbiosis, enhanced the danger of ferroptosis and colitis.

Prior research has demonstrated that antibiotic therapy using neomycin, metronidazole, or ciprofloxacin, prevents the incidence of colitis. A discount in colonic inflammation was observed in germ-free mice (control) and those that received antibiotic treatment at 18 weeks of age; nonetheless, impairment in barrier function occurred. Nevertheless, when 8 weeks old mice were subjected to similar antibiotic treatment, exacerbated colitis was observed. These contradictory observations occurred on account of age-associated gut microbial dysbiosis, which induced the pathogenesis of gut inflammation.

Notably, the present study documented that an early-life microbiota depletion on account of antibiotic cocktail treatment intensified DSS-induced colitis. In contrast, mid-life microbiota depletion led to a decreased clinical symptom of colitis upon DSS challenge. This finding is consistent with previous reports that showed early-life microbial dysbiosis in pups increased the danger of colitis later in life. This occurrence might be on account of various reasons. One explanation is the effect of early-life antibiotic treatment causing microbial dysbiosis, causing a decrease within the colonic epithelial cell cytoprotective properties of specific bacteria and their metabolites (e.g., secondary bile acids and short-chain fatty acids). 

Based on 16S rRNA sequencing, it was shown that young mice contained higher levels of plasmalogen-positive species within the colon in comparison with mature adult mice. A discount in colonic plasmalogen-producing bacteria and plasmalogen levels was correlated with reduced dimethyl-acetal (DMA) derivatives in colon contents of DSS-induced colitis mice. Lower fecal plasmalogen levels and reduced ether-linked phospholipids levels were observed in microbiota-depleted mice.

Conclusions

The present study identified microbes essential for an early-life healthy gut microbiota that would reduce the danger of colitis in later life. Plasmalogens play a vital role within the progression of colitis. They will attenuate inflammatory responses and revert the increased colitis susceptibility of mice lacking anaerobic bacteria. In the long run, the underlying mechanism of plasmalogen-positive microbiota to keep up intestinal health have to be elucidated.