Targeting the gut microbiome — the communities of bacteria and other microorganisms that inhabit the gastrointestinal tract — could be a way to treat a range of age-related conditions. Scientists made this conclusion after investigating the effect of transplanting fecal samples from young to aged mice.
People's gut immune response becomes less effective with age. Studies have linked this decline to age-related changes in the gut microbiome. Inflammation, increased frailty, and a predisposition to intestinal illnesses also accompany these changes.
However, researchers at the Babraham Institute in Cambridge, United Kingdom, found that it is possible to rejuvenate the older gut immune system.
Mice have a habit of nibbling each other's droppings. The researchers were surprised to find that just housing aged and young mice together was enough to boost gut immunity in the older animals. Transplanting fecal pellets from young mice into older mice had an even stronger effect.
The team suggests that the findings, which feature in a recent Nature Communications paper, could lead to treatments that promote healthy aging by alleviating many age-related symptoms.
"Our gut microbiomes are made up of hundreds of different types of bacteria," says first study author Marisa Stebegg, "and these are essential to our health, playing a role in our metabolism, brain function, and immune response."
Changes to gut microbiome composition
The complex and diverse communities of microbes that inhabit the gut vary across the different stages of an individual's life.
While many of the fluctuations are harmless and natural, studies have shown that some disturbances in the gut microbiome can have important effects on health and disease.
Some of the most significant changes in gut microbiome composition occur both at the start of life and in advanced age. These periods are also when the immune system is at its weakest.
Older people are more likely to experience exposure to various drugs and antibiotics, as well as changes to diet and the effects of conditions such as constipation. Scientists have linked such changes to alterations in both the composition and function of the gut microbiome.
"This change in microbial composition with age," write the study authors, "occurs in parallel with a decline in function of the gut immune system; however, it is not clear whether there is a causal link between the two."
For their investigation, Stebegg and her colleagues focused on Peyer's patches. These are follicles in the gut's lymphoid tissue that act as "immune sensors of the intestine."
Peyer's patches and germinal centers
As a result of "cross talk" between gut bacteria and immune cells, Peyer's patches can trigger the immune system to either tolerate or attack perceived threats. The fine-tuning of this function takes place in germinal centers inside the patches and ensures that defense against infection does not compromise "immunological tolerance."
Studies have shown that there is a relationship between germinal center responses and the gut microbiome. Stebegg and her colleagues note that some of these studies' findings have clearly indicated that germinal center responses can influence the gut microbiome.
What these previous studies have not shown, in the case of age-related decline in gut function specifically, is whether the microbiome influences the germinal center response or whether the germinal center response influences the gut microbiome.
When they compared the Peyer's patches of aged mice to those of young mice, the researchers found that the aged mice had a "diminished" germinal center response.
However, when they ran the same comparison between aged mice and young mice that had shared the same environment, they found that cohousing appeared to have "rescued" the germinal center reaction in the aged mice.
The researchers also noted that the aged mice's germinal center reaction was even stronger following fecal transplantation from the younger mice.
The team concludes that the "age-dependent defect" in the immune response of the gut "is not irreversible."
"Our immune system is constantly interacting with the bacteria in the gastrointestinal tract."