Clostridium Scindens in the Centenarian Gut Microbiome Reduces the Impact of Intestinal Aging
The ability to accurately determine the composition of the gut microbiome via 16S rRNA sequencing is resulting a great deal of very interesting data on differences in the gut microbiome that are characteristic of aging, age-related diseases, and long-lived individuals. Here, researchers report that centenarians tend to have more Clostridium scindens in their gut microbiome, and demonstrate in aged mice that a metabolite produced by this bacterial species reduces intestinal barrier dysfunction. That the intestinal barrier becomes more leaky with age is an important contributing cause of chronic inflammation and other forms of dysfunction caused by the presence of unwanted bacteria, metabolites, and other molecules in the circulatory system and tissues throughout the body.
Microbial networks and keystone taxa play pivotal roles in maintaining gut microecological stability and host homeostasis, irrespective of their abundance. However, most previous studies of aging-associated gut microbiota have relied on abundance-based analyses, largely overlooking microbial networks and microbe-host interactions. Here, we employed a co-occurrence network approach to identify keystone taxa during aging in humans and mice. We found that centenarians harbor distinctive keystone taxa dominated by members of Clostridium, of which Clostridium scindens (C. scindens) can significantly enhance microbial network stability, probably contributing to longevity and reduced susceptibility to age-related diseases.
Mechanistically, C. scindens produces indole-3-acetic acid (IAA) from tryptophan via the enzymes amidase (AMIE) and aldehyde dehydrogenase (ALDH). Oral administration of either C. scindens or IAA effectively mitigates intestinal aging by restoring gut barrier dysfunction in aged mice. Further analysis revealed that C. scindens-derived IAA restores intestinal dysfunction through activation of aryl hydrocarbon receptor (AHR) signaling, leading to upregulation of intestinal CLDN10, a key tight junction protein. Structurally, IAA enhances Claudin-10 transcription by promoting AHR binding to its promoter region.
Our findings provide new insights into the characterization of microbial networks in centenarians and highlight that C. scindens and IAA may contribute to healthy longevity by promoting gut microecological stability and host homeostasis.