Gut microbiota and aging: state of the art

• What is already known on this topic
  Studies show a correlation between the composition of the gut microbiota and cognitive performance, frailty and comorbidity of the elderly.

• What this research adds
  This review article summarizes the current state of understanding on the role played by the gut microbiota in the aging process.

• Conclusions
  Looking at the mutual influence of microbiota products, inflammation mediators and the immune system, the modulation of gut microbiota may help to facilitate a physiological and non-pathological aging process and, perhaps, to contrast the progression of degenerating mechanisms.

Aging as an inflammatory condition

The aging process leads to a generalized decline of physiological functions, but what leads to the establishment of the aging process? The deterioration of the immune system, called immunosenescence, seems to play a key role.

Immunosenescence results in the establishment of a state of basal inflammatory activity. Now, this state of inflammation seems to be correlated with both morbidity and mortality in the elderly people, and is a major risk factor for most age-associated pathologies; hence the coining of the term “inflammaging”.

Inflammaging describes a low-grade pro-inflammatory state characteristic of the aging process. It has been posited that this predisposes the organism to the development of various age-related diseases, such as Alzheimer’s and Parkinson’s diseases.

Gut microbiota and aging

The gastrointestinal tract is not immune to the aging process. With age, alterations occur, which can result in the development of gastrointestinal pathologies. Now, these alterations are also associated with changes in the gut microbiota.

Indeed, studies have shown a decreased diversity of the gut microbiota composition in the elderly, in particular a reduced abundance of species producing butyrate. It has been shown that short chain fatty acids (SCFAs) such as acetate, propionate and butyrate play an important role in modulating the immune response by inhibiting the production of inflammatory mediators. In other words, the diminution in the production of SCFAs can explain immunosenescence and lead to the increase frailty in the elderly.

Factors affecting the gut microbiota in the elderly

Several factors can induce changes of the gut microbiota composition in an individual, in particular: race and ethnicity, the use of drugs, and life-style and diet habits.

In particular, studies have shown a link between the composition of the gut microbiota and how diverse and healthy the diet is: a less diverse diet is linked to a decrease in the gut microbiota diversity, which is correlated with increased frailty, inflammatory markers and impaired health parameters.

A prolonged antibiotic therapy also influences the modulation of the gut microbiota, in particular the formation and deposition of the amyloid protein, a protein playing a role in the Alzheimer’s disease.

Gut microbiota and inflammaging

A study performed on mice showed that inflammaging can be correlated with the inflammatory response induced by lipopolysaccharide (LPS), one of the most important products of the microbiota.

Besides, in vivo and in vitro studies have shown a correlation between the deposition of amyloid-ß (Aß) and tau in the brain – which is linked with the Alzheimer’s disease – and the production of LPS.

There is also some evidence that compounds derived from the gut microbiota can activate macrophages to a pro-inflammatory state, which seems to be responsible for atherosclerosis. This process could cause the development of cardiovascular disease as well as vascular dementia.

Oral administration of Lactobacillus brevis OW38 to aged mice has been shown to strengthen intestinal barrier tight junctions, reduce the levels of circulating LPS and the expression of pro-inflammatory cytokines.

However, whether the stable modification of the gut microbiota could be obtained and what its long-term effects could be still needs to be clarified. Future research should be designed to better understand the correlation between gut microbiota, the aging process and the degenerative diseases typical of the elderly.