What is already known
Long-term HIV infection is known to accelerate biological aging and cause persistent inflammation. Although inflammation is attributed in part to alterations of the gut microbiota, how long-term HIV infection affects biological age remains unclear.
What this research adds
Researchers analyzed colon, ileum, stool and blood samples from people living with chronic HIV infection. Compared with controls, people with chronic HIV infection had higher intestinal abundance of inflammatory bacteria, such as Catenibacterium and Prevotella, whereas they lacked Subdoligranulum, Erysipelotrichaceae and other gut microbes known for producing anti-inflammatory metabolites. In people with chronic HIV infection, alterations of the gut microbiota were also associated with increased intestinal permeability — a phenomenon known as leaky gut — and faster biological aging, as measured by the pattern of chemical tags attached to the DNA.
Conclusions
The findings suggest that specific microbial signatures are associated with accelerated biological aging.
Long-term HIV infection is known to accelerate aging, but the mechanisms underlying this phenomenon are poorly understood. A new study shows that increased intestinal permeability — or leaky gut — is linked to faster aging in people with HIV.
The work, published in the journal Microbiome, also suggests that specific microbial signatures are associated with accelerated biological aging — a finding that may inform approaches to mitigate accelerated aging and its associated health complications, the researchers say. “Our work is just the beginning of an exciting journey into enhancing health and longevity,” says study co-senior author Abdel-Mohsen at the Wistar Institute in Philadelphia, Pennsylvania.
Besides accelerated aging, long-term HIV infection can cause persistent inflammation, which is in part attributed to alterations of the gut microbiota. Because chronic inflammation may speed up aging, Abdel-Mohsen and his team suspected that a leakage of gut bacteria into the bloodstream could be linked to accelerated aging in people with HIV. So, the researchers set out to analyze colon, ileum, stool and blood samples from 25 people with chronic HIV infection and 23 people living without HIV.
Gut inflammation
Compared with controls, people with chronic HIV infection had higher abundance of inflammatory bacteria, such as Catenibacterium and Prevotella, in their guts. Catenibacterium, Prevotellaceae and Enterobacteriaceae can break down the amino acid tryptophan and have been associated with accelerated biological aging. An increased breakdown of tryptophan can lead to the buildup of toxic byproducts, studies have shown.
However, the authors note, “more research is needed to determine the specific bacterial species initiating tryptophan catabolism and to understand if these associations with biological aging are causative.”
Relative to controls, people with HIV lacked Subdoligranulum, Erysipelotrichaceae and other gut microbes known for producing anti-inflammatory metabolites, including the short-chain fatty acid (SCFA) butyrate, which contributes to bolster the integrity of the intestinal barrier. Besides SCFAs, the researchers identified associations between other microbial metabolites with anti-inflammatory properties and a reduced rate of aging.
Leaky gut
In people with chronic HIV infection, alterations of the gut microbiota were associated with increased intestinal permeability, as measured by the pattern of chemical tags attached to the DNA.
Microbial translocation from the gut also correlated with faster biological aging and increased levels of inflammatory markers, the researchers found.
The findings indicate that specific bacterial signatures are linked to accelerated aging at both the systemic and intestinal levels. However, future investigations will have to assess the causes underlying this phenomenon. What’s more, Abdel-Mohsen says, “there’s a crucial need to create strategies to prevent intestinal dysbiosis and gut leakiness and to determine how these strategies could affect an individual’s biological age.”
