Gut microbes contribute to age-associated inflammation, mouse study finds

April 12, 2017
This visual abstract represents the findings of Thevaranjan et al. who, using young and old germ-free and conventional mice, demonstrate that age-related microbiota changes drive intestinal permeability, age-associated inflammation, and decreased macrophage function. Reducing TNF levels rescues microbiota changes and protects old mice from intestinal permeability. Credit: Thevaranjan et al./Cell Host & Microbe 2017

Inflammation increases with age and is a strong risk factor for death in the elderly, but the underlying cause has not been clear. A study published April 12 in Cell Host & Microbe reveals that gut microbes are one of the culprits behind age-associated inflammation and premature death in mice. Imbalances in the composition of gut microbes in older mice cause the intestines to become leaky, allowing the release of bacterial products that trigger inflammation and impair immune function.

"To date, the only things you can do to reduce your age-associated are eat a healthy diet, exercise, and manage any chronic inflammatory conditions to the best of your ability," says senior author Dawn Bowdish of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University. "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."

Age is associated with an increase in levels of tumor necrosis factor (TNF) and other pro-inflammatory cytokines in the bloodstream and tissues. Individuals with high levels of these inflammatory molecules are more likely to be frail, hospitalized, and less independent; are more susceptible to certain types of infections; and have a variety of chronic, late-life diseases such as dementia and cardiovascular disease, as well as higher death rates. Some have proposed that age-associated inflammation is caused by accumulating wear and tear on our immune cells, while others have suggested that it is caused by dealing with chronic viral infections. But evidence supporting these hypotheses has been elusive, and the underlying cause of age-associated inflammation has remained unknown.

Bowdish and her colleagues raised in germ-free conditions and compared them to their conventionally raised counterparts. Strikingly, the 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. Moreover, a higher proportion of germ-free mice lived to the ripe old age of 600 days, and macrophages derived from older germ-free mice maintained anti-microbial activity. Taken together, these 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 , and reduce lifespan.

Additional experiments showed 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 were not observed. Moreover, treatment with an anti-TNF drug approved for human use reversed age-related changes in the microbiome.

"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 says. "We also believe that targeting age-associated inflammation will improve immune health and are investigating repurposing drugs that are already on the market and developing novel strategies or therapeutics to this effect."

In future studies, Bowdish and her collaborators will try to identify the good bacteria that maintain gut integrity with age as well as the bad bacteria that cause the gut to become leaky. They are also trying to understand how early in life some of these changes in the microbiota start occurring so that they could try to intervene before they are severe enough to alter immune function.

In the end, this research could lead to new strategies for manipulating the microbiome to improve intestinal health and decrease age-associated inflammation. "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 says.

Explore further: Studying 'inflamm-aging': Monocytes, cytokines, and susceptibility to pneumonia

More information: Cell Host & Microbe, Thevaranjan and Puchta et al.: "Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation and macrophage dysfunction" http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30112-9 DOI: 10.1016/j.chom.2017.03.002

Related Stories

Studying 'inflamm-aging': Monocytes, cytokines, and susceptibility to pneumonia

January 14, 2016
The chronic state of low-level inflammation seen in many elderly individuals (sometimes called "inflamm-aging"), is associated with diseases such as cardiovascular disease and dementia, as well as susceptibility to infections, ...

Scientists identify mechanisms driving gut bacterial imbalance and inflammation

February 8, 2017
A study led by UT Southwestern Medical Center researchers has uncovered key molecular pathways behind the disruption of the gut's delicate balance of bacteria during episodes of inflammatory disease.

Accelerated immune aging may contribute to obesity-linked metabolic disease

November 7, 2016
Obese individuals are at an elevated risk of developing comorbid cardiovascular and metabolic diseases, such as type 2 diabetes. Some research suggests that these comorbid diseases develop in response to chronic inflammation ...

Immune cells' bacteria may fight chronic inflammation

March 17, 2016
A population of bacteria inhabits human and mouse immune cells and appears to protect the body from inflammation and illness, Weill Cornell Medicine scientists discovered in a new study. The findings challenge conventional ...

Common food additive promotes colon cancer in mice

November 7, 2016
Emulsifiers, which are added to most processed foods to aid texture and extend shelf life, can alter intestinal bacteria in a manner that promotes intestinal inflammation and colorectal cancer, according to a new study.

Over-the-counter pain reliever may restore immune function in old age

September 2, 2014
New research involving mice suggests that the key to more youthful immune function might already be in your medicine cabinet. In a report published in the Journal of Leukocyte Biology scientists show that macrophages from ...

Recommended for you

Evidence found of oral bacteria contributing to bowel disorders

October 20, 2017
(Medical Xpress)—An international team of researchers has found evidence that suggests certain types of oral bacteria may cause or exacerbate bowel disorders. In their paper published in the journal Science, the group describes ...

New compound discovered in fight against inflammatory disease

September 22, 2017
A 10-year study by University of Manchester scientists for a new chemical compound that is able to block a key component in inflammatory illness has ended in success.

Asthma researchers test substance from coralberry leaves

September 14, 2017
The coralberry could offer new hope for asthmatics. Researchers at the University of Bonn have extracted an active pharmaceutical ingredient from its leaves to combat asthma, a widespread respiratory disease. In mice, it ...

Respiratory experts urge rethink of 'outdated' asthma categorisation

September 12, 2017
A group of respiratory medicine experts have called for an overhaul of how asthma and other airways diseases are categorised and treated.

New 'biologic' drug may help severe asthma

September 7, 2017
(HealthDay)—A "biologic" drug in development to treat severe asthma reduces the rate of serious attacks by about two-thirds compared to a placebo drug, according to preliminary research findings.

Songbird study shows how estrogen may stop infection-induced brain inflammation

August 31, 2017
The chemical best-known as a female reproductive hormone—estrogen—could help fight off neurodegenerative conditions and diseases in the future. Now, new research by American University neuroscience Professor Colin Saldanha ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.