Could Gut Microbes be Linked to Age-Related Inflammation?

Gut microbes are found to be associated with age-related inflammation, providing novel therapeutic strategies to counter inflammation.

Highlights:

The microbes present in the gut play an important role in the development of inflammation as age advances.
Certain microbes are found to leak out of the gut and result in inflammation.
Germ-free environment showed reduced level of intestinal permeability and lower inflammatory markers.

The body’s immune system begins to gradually deteriorate with advancement in age. This is associated with systemic inflammation, which is one of the strong risk factors of death among the elderly. In a study published in the journal Cell Host & Microbe, gut microbes have been shown to be associated with age-associated inflammation as well as premature death.

Imbalances are caused in the intestine due to changes in the composition of gut microbes. This in turn, lead to leaky intestines that release bacterial products, triggering inflammation.

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‘Maintaining a healthy gut microbiome is essential for controlling inflammation with advanced age.’

Dr. Dawn Bowdish from the McMaster University’s Michael G. DeGroote Institute for Infectious Disease Research said, that current practices to lower age-related inflammation involve maintaining a healthy diet, exercising and managing the chronic inflammation. The study conducted by the research team shed some light on the role of gut microbes, raising the possibility of using drugs or pre-biotics that would lower the permeability of the gut. This will help retain the microbes and lower the risk of age- related inflammation.

Age Associated Inflammation:

Aging is found to be associated with

Chronic low-grade inflammation
The levels of interleukin (IL)–6 and tumor necrosis factor–α (TNF-α) are 2–4-fold higher in the elderly than among middle-aged adults
Tissue samples from senescent animals showed that there were elevated levels of activated NFkB
C-reactive protein levels are higher in bronchoalveolar lavage fluid, and plasma samples in elderly persons, than among healthy young adults
Persistent low-grade inflammation of the lungs is present in elderly persons.
Elderly individuals with high levels of inflammation have a higher likelihood of being frail, with greater dependency and chances of being hospitalized
They are found to be prone to certain infections including pneumonia
They have a greater risk of dementia, cardiovascular disease and death

Cause for Age-Related Inflammation:

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Macrophages are known for their Pac Man-like ability to gobble up pathogens and cellular debris in order to thwart infection.

The research team raised mice in a germ-free environment, and compared these mice with mice that were grown in a normal environment.

What did the study reveal?

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The study showed that -

Mice that were grown in a germ-free environment did not show any change in the intestinal permeability or in the level of pro-inflammatory cytokines or in the number of bacterial products.
There were more number of mice, grown in the germ-free environment, that lived for about 600 days or more, an advanced age for mice, when compared with mice that were grown in a normal environment.
The macrophages that were isolated form such old germ-free mice retained microbial activity.
The age associated changes that occur in the gut microbiome led to weakening of the intestinal barrier with impaired immune function and reduced lifespan.

Bi-direction Association:

Age-related inflammation and the microbiome are bidirectional. Further experiments showed that

In mice that were deficient in tumor necrosis factor (TNF), there were no changes in the composition of the gut microbes.
When mice grown in a normal environment were treated with anti-TNF drug, the age-related changes in the microbiome were reversed.

Dr. Bowdish said that this was probably due to reduction in inflammation that led to an improvement in the immune function. This helped in maintaining a healthy crop of gut microbiome. The research team stated that addressing the age-related inflammation will improve the immune health of the individual. Further research aims at identifying the good bacteria that help maintain gut health and the bad bacteria that give rise to the leaky gut. Identifying the onset of the inflammation would help in developing strategies that prevent further increase and can be used to take pro-active steps.

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Cancerous mutations tend to alter healthy cells in ways that help them survive conditions of inflammation in the bone marrow.

The current research can be used to identify pro and pre-biotic treatment methods that will control age-related inflammation and lower the risk of associated diseases.

Caffeine Found to Lower Age Related Inflammation:

In a similar study conducted by a research team from Stanford University, metabolites or breakdown products of nucleic acids were found to circulate in the blood and increase inflammation. This increase in inflammation was found to be associated with cardiovascular health. A research team led by Dr. Mark Davis from Stanford University showed, that caffeine could lower the nucleic acid metabolites and lower the level of inflammation.

Targeting inflammation using novel strategies could help in reducing age associated inflammation and lower the risk of diseases. This will help in improving the quality of life of people during the advanced stages of life.

References:

Caffeine may counter age-related inflammation - (https://med.stanford.edu/news/all-news/2017/01/caffeine-may-counter-age-related-inflammation-study-finds.html)
A cause of age-related inflammation found - (https://emb.carnegiescience.edu/cause-age-related-inflammation-found-5095)
Netusha Thevaranjan, Alicja Puchta, Christian Schulz, Avee Naidoo, J.C. Szamosi, Chris P. Verschoor, Dessi Loukov, Louis P. Schenck, Jennifer Jury, Kevin P. Foley, Jonathan D. Schertzer, Maggie J. Larché, Donald J. Davidson, Elena F. Verdú, Michael G. Surette, Dawn M.E. Bowdish. Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction. Cell Host & Microbe, 2017; 21 (4): 455 DOI: 10.1016/j.chom.2017.03.002

Source-Medindia