Gut microbes play role in age-related inflammation: Mouse study

Findings could offer insight into diseases like Parkinson’s

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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One young person is seen drawing a digestive tract and its microbiome on the abdominal area of another.

Gut microbes may play an important role in driving the low-grade inflammation that naturally occurs with aging and is exacerbated in conditions like Parkinson’s disease, according to research in mice.

Older mice were found to have a distinct immune signature reflective of inflammation in the gastrointestinal tract that was associated with the microbial contents of their guts. When contents from their intestines were transplanted into younger mice, they experienced similar inflammation. The microbiomes of aged mice were also slower to bounce back after treatment with antibiotics.

Researchers said the findings offer insights into how age-related alterations in the gut microbiome can influence health and inflammation. This could also ultimately inform research on mechanisms underlying inflammatory age-related conditions like Parkinson’s.

“Gut microbiota immunogenic signatures should be … considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations,” the researchers wrote.

The study, “Aging amplifies a gut microbiota immunogenic signature linked to heightened inflammation,” was published in Aging Cell.

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Seeking link between aging and inflammation

Increases in low-grade inflammation are a part of the aging process, but may be significantly exacerbated in age-related neurodegenerative diseases like Parkinson’s and Alzheimer’s disease. The mechanisms underlying the shift in age-related inflammation are not entirely known.

“There’s a kind of debate as to what drives this, what is the major cause of the aging-induced inflammatory state,” Jacob Allen, PhD, assistant professor in the Department of Kinesiology and Community Health at the University of Illinois Urbana-Champaign and one of the study’s senior authors, said in a university press release.

The gut microbiome — the collection of bacteria, viruses, and fungi that populate the gastrointestinal tract — changes throughout the lifespan and has been linked to aging and age-related diseases. It has been found to be dysregulated in people with Parkinson’s disease, for whom the microbiome may favor an inflammatory state.

Researchers have proposed that gut microbiome alterations could drive age-related inflammation. The lining of the gut is specially designed as a barrier to keep molecules in the gut from leaking out into the bloodstream, including bacteria and toxins. When this barrier becomes disrupted, those things more easily access the rest of the body.

“The things that are in our gut are supposed to be kept separate from the rest of our system,” said Thomas Buford, PhD, a professor in the University of Alabama at Birmingham’s Department of Medicine and the study’s other senior author. “If they leak out, our immune system is going to recognize them,” Buford said. “And so then the question was: ‘Is that a source of inflammation?’”

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Microbiome influences inflammation

The scientists explored whether an aged microbiome might spur inflammation, performing a series of experiments in mice.

Examining the colon contents of both aged and young mice, they found that older mice had a distinct microbiome composition compared with younger ones, consistent with previous studies.

The aging microbiome was also linked to signs of inflammation, immune cell infiltration, and barrier disruption in the colon. In particular, experiments showed increased signaling of toll-like receptor 4, or TLR4, an important inflammatory mediator that’s responsive to bacteria, associated with the microbiome.

The scientists then transplanted intestinal contents from the older mice into younger mice that did not have microbiomes of their own. After transplant, those young mice developed signs of inflammation in the colon similar to that which occurred in the aged mice, supporting the idea that the microbiome can directly influence inflammation.

The researchers wanted to also look at how the mice’s microbiomes responded to antibiotics with age. Antibiotics, commonly used to fight off bacterial infections, have a substantial impact on the composition of the microbiome, but this usually normalizes after treatment has stopped.

Young and old mice were treated with antibiotics in their drinking water for a week. The microbiomes of the older mice seemed to have an altered recovery from antibiotics, which corresponded with elevations in various markers of inflammatory status.

“It appears that as we age our microbiome might be less resilient to antibiotic challenges,” Allen said. “This is important because we know that in the U.S. and other Western societies, we’re increasingly exposed to more antibiotics as we age.”

Additional studies are needed to better understand the role of the microbiome in age-related inflammation, and how this contributes to chronic diseases like Parkinson’s, the researchers said.