Healthy ageing – the right changes in the gut microbiome support longevity

One of the world’s leading microbiologists in gut and ageing research is Ravinder Nagpal. Owning numerous honours, he is today doing research at Wake Forest School of Medicine, Centre for Diabetes, Obesity & Metabolism, Department of Microbiology & Immunology. According to Nagpal, there are two phases in the course of one’s life that the microbiome appears to be particularly vulnerable: early childhood and high age. Meanwhile, we know that during these very phases the gut microbiome of a healthy person alters its composition whereas it is more or less stable from late childhood to adolescence. For Nagpal, this indicates that our health depends a lot on an intact gut microbiome (1).

Composition of gut microbiome is key

In February 2021, a team of scientists of the Institute of System Biology in Seattle (USA) published a study on correlations between health in high age and the composition of the gut microbiome in Nature Metabolism. This study, too, supports Nagpals claim that healthy ageing and gut microbiome correlate and moreover stresses that one of the key factors is an adequate and clear shift in the microbial composition between adolescence and senior age.

The publication is based on a survey from 2012 that screened 531 individuals’ stool samples. The samples were taken from children and adults from the Amazon area in Venezuela, a rural region of Malawi and a US metropolitan area (3). It showed that after an intense phase of development in the first three years of a human’s life, the gut microbiome is relatively stable throughout the entire life with all people irrespective of their origin. The probes of traditional Venezuela and Malawi people, however, showed tremendous differences to those of the US compare group regarding type of bacteria found. Those differences should be a matter of concern, by all means, but will not be in the centre of attention of this article.

The Seattle scientists now tried to find a pattern in the gut microbiome composition that comes with both high age and health. The team screened 9,000 samples of adults between 18 and 101 years of age, including 900 samples of seniors that underwent frequent check-ups. The screening identified a number of critical factors.

Critical factors for healthy ageing

While the gut microbiome is more or less stable from childhood to adulthood, the Wilmaski and his co-workers observed that a changing microbiome was a feature of those seniors that were in good health. An increasing individualization showed that is evidenced in the metabolic products in the blood. Furthermore, seniors with outstanding health showed a striking reduction of Bacteroides. They furthermore show high levels of vitamin D and low levels of blood lipid values, such as LDL cholesterol and triglycerides.

Also, indol, a metabolic product of the commensal microbiota was identified as an indicator of healthy ageing and is associated as a factor for reduced frailty. (Commensal microbioata are those that feed on metabolic products of a host without causing damage). Studies with mice and flies, however, showed that increased levels of indol is not a market of longevity, but the life quality of the individual was far better that that of the comparison group with low indol levels due to reduced frailty (4).

A similar study on 100-year old Italians showed a similar result for humans. Changes in the microbiome is a marker for longevity. Key components turned out to be markers for longevity in the urine, such as PAC (Phenylacetylglutamine) and PCS (p-Kresolulfat) that 100-year olds excrete more frequently than other old people. Moreover, 100-year-olds show higher rates in 2-HB (2-Hdroxybenzoate), which is found in most fruits and vegetables and has anti-inflammatory effects (5).

Another study by Kim and Jawinski (2018) identified impaired communication between microbiome and host as reason for frailty and reduced life expectancies (6). Generally speaking, moderate exercise and a healthy diet rich in fibre rich foods seems to support a microbiome that is adapted to the higher age. All authors, however, stress that cause and effect of that correlation has not yet been firmly established.

What if the microbiome does not change?

Wilmaski. Et al. zeroed in on a group of subjects whose microbiomes did not change when they got older. Higher cholesterol and triglyceride levels in the blood as well as lower levels in vitamin D were some of the hallmarks in this group. They were also not as fit as their counterparts with adequately altered microbiomes. The scientists involved in this study claimed that above all the prevalence of bacteroides made a difference.

One of the co-authors, Dr. Saen M. Gibbons, summarizes it as follows: In his younger years, a human produces a lot of mucus that bacteroides bacteria feed on. Over the years, the production ceases. This is why it makes sense that the amount of bacteroides declines, just like it does in the healthy people in their 40s screened in the study. But if that shift does not happen, the bacteroides bacteria eat up too much of the mucus, rendering the gut lining less protected. This sets the stage for the development of a number of inflammatory reactions resulting in chronic diseases that “unhealthy ageing” usually is associated with (6). Diabetes, arthritis, and even some kinds of cancer are associated with increased levels of inflammation.

What can we do?

The authors admit that diet did not play a role in their evaluations and should be paid further attention to in follow-up studies. Gibbons speculates that a diet high in fibre rich foods might deliver sufficient food for the bacteroides and prevent the mucous membrane from being attacked. He also sees therapies for reducing a surplus in bacteroides in the nearer future. A possible approach with metformin was presented in an online conference by geriatrist Prof. Christoph Kaleta, head of the work group „medical systems biology“ at the Institute for Experimental Medicine of the Christian-Albrechts-Universität in Kiel (7).

Gibbon’s advice to all elderly people until the therapy is finalized – and he is doing this for himself, as well: healthy diet and a good deal of exercise. “I have started eating a lot more fibre since I began studying the microbiome,” he said. “Whole foods like fresh fruits and veggies have all the complex carbohydrates that our microbes like to eat. So, when you’re feeding yourself, think about your microbes too.” (8)

Sources / References:

1. Nagpal R, Mainali R, Gut microbiome and aging: Physiological and mechanistic insights, Nutr Healthy Aging (2018), https://pubmed.ncbi.nlm.nih.gov/29951588/

2. Wilmanski T, Diener C, et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat Metab (2021). https://www.nature.com/articles/s42255-021-00348-0#citeas

3. Yatsunenko T, Rey F, et al. Human gut microbiome viewed across age and geography. Nature (2012), https://www.nature.com/articles/nature11053#citeas

4. Sonowall R, Swimm A, et.al., Indoles from commensal bacteria extend healthspan. PNAS (2017), https://www.pnas.org/content/114/36/E7506

5. Collino S, Montoliu I, et.al, Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PLoS One (2013), https:/ /pubmed.ncbi.nlm.nih.gov/23483888/

6. Kim S, Jawinksi S, The Gut Microbiota and Healthy Aging: A Mini-Review, Gerontology (2018), https://pubmed.ncbi.nlm.nih.gov/30025401/

7. Kaleta Ch, Verändertes Mikrobiom bei Hochaltrigen: Wie die Darmflora das Altern beeinflussen kann, DGG (2020), https://www.dggeriatrie.de/images/Dokumente/200901-dgg-pressemeldung-keynote-christoph-kaleta-mikrobiom-bei-hochaltrigen.pdf

8. O´Connor A, A Changing Gut Microbiome May Predict How Well You Age, NY Times (2021) https://www-nytimes-com.cdn.ampproject.org/c/s/www.nytimes.com/2021/03/18/well/eat/microbiome-aging.amp.html