The Importance of Microbiota in Healthy Aging

Figure 1.  The complex interplay of dietary elements, the microbiota,
and the host can be beneficial or detrimental to host health.

Recent estimates suggest your body houses some 30 trillion bacteria ^[4] and about 1 quadrillion viruses.  In essence we're little more than walking microbe colonies.

These organisms perform a wide variety of functions, including

• Assisting in the digestion of food
• Regulating the enteric nervous system, which rules the digestive tract
• Orchestrating the immune response
• Helping modulate many aspects of inflammation
• Playing a large role in brain and mental health, as the gut and the brain are intricately connected

The gut microbiome has important effects on human health, yet its importance in human aging remains unclear until recently.  In this article, we will cover two case studies on the importance of gut microbiome in healthy aging.

Video 1.  Microbiome: The Inside Story (YouTube link)

Microbiome and Healthy Aging

Healthy Aging  = a healthy and diverse microbiota

The recent consensus is that, in aggregate, the diversity of the gut microbiota declines with age,^[7] although whether this is associated with healthy aging is controversial and the delineation of what is normal in different cohorts are still not clear.

The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty.^[14]

 
One research showed several surprising results compared to other cohorts.^[5,6]

1. The overall microbiota composition of the healthy aged group was similar to that of people decades younger. 
2. The major differences between groups in the gut microbiota profiles were found before age 20. 
3. The gut microbiota differed little between individuals from the ages of 30 to >100. 
4. The gut microbiota of males appeared to be more variable than that of females. 

Taken together, the present findings suggest that the microbiota of the healthy aged in this cross-sectional study differ little from that of the healthy young in the same population, although the minor variations that do exist depend upon the comparison cohort.

We speculate that this similarity is a consequence of an active healthy lifestyle and diet, although cause and effect cannot be ascribed in this (or any other) cross-sectional design. One surprising result was that the gut microbiota of persons in their 20s was distinct from those of other age cohorts, and this result was replicated, suggesting that it is a reproducible finding and distinct from those of other populations.

While their cross-sectional cohort precludes the assignment of cause and effect, their results suggest that diet and lifestyle choices consistent with healthy aging even into the 10th decade of life include a healthy and diverse microbiota.

Healthy Aging  = Increasing Compositional Uniqueness of the Gut Microbiome

In a recent study, scientists demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age.  Their analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy aging, which is characterized by distinct microbial metabolic outputs in the blood.^[10]

They leverage three independent cohorts comprising over 9,000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. 

In older age (over ~80 years), healthy individuals show continued microbial drift towards a unique compositional state, whereas this drift is absent in less healthy individuals. 

The identified microbiome pattern of healthy aging is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. 

References

1. Microbiomes could hold keys to improving life
2. How Gut Bacteria Are Shaking Up Cancer Research
3. Fat for Fuel
4. R. Sender, S. Fuchs, and R. Milo, "Revised Estimates for the Number of Human and Bacteria Cells in the Body," PLoS Bilogy, 14, no.8 (2016)
5. ‘Ridiculously Healthy’ Elderly Have the Same Gut Microbiome as Healthy 30 Year-Olds
6. The Gut Microbiota of Healthy Aged Chinese Is Similar to That of the Healthy Young
7. Lynch SV, Pedersen O. 2016. The human intestinal microbiome in health and disease. N Engl J Med 375:2369–2379.
8. Microbiome: The Inside Story
9. Researchers Discover Gut-Heart Connection in Coronary Artery Disease
10. Gut microbiome pattern reflects healthy ageing and predicts survival in humans
11. K Riehle, C Coarfa, A Jackson, J Ma, A Tandon, S Paithankar, S Raghuraman, T A Mistretta, D Saulnier, S Raza, M A Diaz, R Shulman, K Aagaard, J Versalovic, A Milosavljevic. The Genboree Microbiome Toolset and the analysis of 16S rRNA microbial sequences. BMC Bioinformatics. 2012;13 Suppl 13:S11.
12. V Hughes. Microbiome: Cultural differences. Nature. 2012 Dec 6;492(7427):S14-5.
13. C D Simões, J Maukonen, J Kaprio, A Rissanen, K H Pietiläinen, M Saarela. Habitual dietary intake is associated with stool microbiota composition in monozygotic twins. J Nutr. 2013 Apr;143(4):417-23.
14. M J Claesson, I B Jeffery, S Conde, S E Power, E M O'Connor, S Cusack, H M Harris, M Coakley, B Lakshminarayanan, O O'Sullivan, G F Fitzgerald, J Deane, M O'Connor, N Harnedy, K O'Connor, D O'Mahony, D van Sinderen, M Wallace, L Brennan, C Stanton, J R Marchesi, A P Fitzgerald, F Shanahan, C Hill , R P Ross, P W O'Toole. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012 Aug 9;488(7410):178-84.
15. J Maukonen, M Saarela. Human gut microbiota: does diet matter? Proc Nutr Soc. 2015 Feb;74(1):23-36.
16. I Zilber-Rosenberg, E Rosenberg. Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution. FEMS Microbiol Rev. 2008 Aug;32(5):723-35.
17. J R Goldsmith, R B Sartor. The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health, and therapeutic implications. J Gastroenterol. 2014 May;49(5):785-98.
18. D M Saulnier, S Kolida, G R Gibson. Microbiology of the human intestinal tract and approaches for its dietary modulation. Curr Pharm Des. 2009;15(13):1403-14.
19. K M Tuohy, C Gougoulias, Q Shen, G Walton, F Fava, P Ramnani. Studying the human gut microbiota in the trans-omics era--focus on metagenomics and metabonomics. Curr Pharm Des. 2009;15(13):1415-27.
20. D J Triggle. Nous sommes tous des bacteries: implications for medicine, pharmacology and public health. Biochem Pharmacol. 2012 Dec 15;84(12):1543-50.
21. R Goodacre. Metabolomics of a superorganism. J Nutr. 2007 Jan;137(1 Suppl):259S-266S.
22. R D Sleator. The human superorganism - of microbes and men. Med Hypotheses. 2010 Feb;74(2):214-5.
23. R D Fleischmann, M D Adams, O White, R A Clayton, E F Kirkness, A R Kerlavage, C J Bult, J F Tomb, B A Dougherty, J M Merrick, et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496-512.
24. D Ornish, M J Magbanua, G Weidner, V Weinberg, C Kemp, C Green, M D Mattie, R Marlin, J Simko, K Shinohara, C M Haqq, P R Carroll. Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8369-74.
25. L Liu, Y Li, S Li, N Hu, Y He, R Pong, D Lin, L Lu, M Law. Comparison of Next-Generation Sequencing Systems. J Biomed Biotechnol. 2012;2012:251364.
26. Food for thought about the immune drivers of gut pain
27. Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome
28. Bouhnik Y et al. Effects of Bifidobacterium sp fermented milk ingested with or without inulin on colonic bifidobacteria and enzymatic activities in healthy humans. European Journal of Clinical Nutrition 1996 Apr; 50(4):269-73.
29. Gyawali R et al. The role of prebiotics in disease prevention and health promotion. Chapter 12 in Dietary Interventions in Gastrointestinal Diseases, 2019. Pages 151-67.
30. Mahboobi S et al. Effects of prebiotic and synbiotic supplementation on glycaemia and lipid profile in type 2 diabetes: A meta-analysis of randomized controlled trials. Advanced Pharmaceutical Bulletin 2018 Nov; 8(4):565-74.
31. Nowak A et al. Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens. Regulatory Toxicology and Pharmacology 2015 Dec; 73(3):938-46.
32. The effects of oral microbiota on health (Science Magazine)