New research published in Cell Host & Microbiome suggests that imbalances in the composition of gut microbes in older mice cause the intestines to become leaky, releasing bacterial products that can trigger inflammation, block immune functions and reduce lifespan.
Led by senior author Professor Dawn Bowdish of McMaster University in Canada, the team noted that until while it has been shown that inflammation increases with age and is a strong risk factor for disease and death in the elderly, the underlying cause has not been clear.
"To date, the only things you can do to reduce your age-associated inflammation are to eat a healthy diet, exercise and manage any chronic inflammatory conditions to the best of your ability," said Bowdish.
"We hope that in the future we will be able use drugs or pre- or probiotics to increase the barrier function of the gut to keep the microbes in their place and reduce age-associated inflammation and all the bad things that come with it."
Previous research has shown as we age, people with high levels of inflammatory molecules are more likely to be frail, hospitalised, and less independent. They are also more susceptible to infections and chronic conditions like dementia and heart disease, the team noted.
Bowdish said the study findings could lead to new strategies to improve intestinal health and immune function in older adults using drugs or nutritional interventions like probiotics and prebiotics.
The Canadian-led team colleagues compared data from two sets of mice: one set raised in germ-free conditions and their conventionally raised counterparts.
Germ-free mice did not show an age-related increase in intestinal permeability or in levels of bacterial products or pro-inflammatory cytokines in the bloodstream, in contrast to conventionally raised mice, said the team.
Furthermore, a higher proportion of germ-free mice lived to the ‘old age’ of 600 days compared to those conventionally reared, and macrophages from older germ-free mice were found to maintain anti-microbial activity.
Taken together, Bowdish and her team say the findings demonstrate that age-related changes in the gut microbiome weaken the intestinal barrier, leading to the release of bacterial products that promote inflammation, impair immune function, and reduce lifespan.
Further tests by the team found that the relationship between inflammation and the microbiome is bidirectional. In TNF-deficient mice, which are protected from inflammation, age-related changes in the composition of gut microbes were not observed. Moreover, treatment with an anti-TNF drug approved for human use reversed age-related changes in the microbiome, they said.
"We assume that this is because if we reduce inflammation, we improve immune function, and if we improve immune function, we maintain the ability to farm a healthy gut microbiota, but we don't know for sure yet," Bowdish said.
"We also believe that targeting age-associated inflammation will improve immune health.”
She added that future studies will aim to identify the good bacteria that maintain gut integrity with age as well as the bad bacteria that cause the gut to become leaky.
"Since age-associated inflammation is linked to so many aspects of unhealthy aging, we predict that these strategies could help keep us healthy, active, and independent as we age," Bowdish said.
Source: Cell Host & Microbiome
Volume 21, Issue 4, Pages 455–466.e4, doi: 10.1016/j.chom.2017.03.002
“Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction”
Authors: Netusha Thevaranjan, et al