The microbiome as a fountain of youth?

Studies on over-100-year-olds underpin the role of the microbiome in aging

The microbiome ages with you

Healthy aging!

The microbiome refers to the totality of the trillions of bacteria, fungi and viruses that colonize our intestines and that have a previously underestimated influence on our health. From a therapeutic point of view, the microbiome represents a new way of maintaining health. The microbiome works best when it has a high diversity of the bacterial community to handle the wide range of tasks. The tasks of the bacteria include, for example the digestion of the food residues in the large intestine, to form a barrier for pathogens that could penetrate the body, to produce certain vitamins, hormones and messenger substances, to promote the development and maturation of the immune system and to support the cells of the intestinal mucosa in their function – in short: to keep us healthy overall. The huge number of bacteria lives in good symbiosis with us. A major product of bacterial metabolism is the short chain fatty acids (SCFA) that leave the intestine. They are absorbed by almost all tissues, including the brain, and develop their health-promoting properties there. The microbiome thus acts over the boundaries of the intestine.

Advancing age is generally accompanied by changes in the gut microbiota. These are characterized by a loss of diversity and many useful, comensal microbes. The microbiome can then no longer perform its tasks and diseases develop. Comparative studies of Chinese and Italians over the age of 100, who have been proven to have successfully aged healthily, despite all the differences due to genetics, diet and environmental conditions, showed striking similarities of certain types of bacteria that may be responsible for healthy aging (although it is still too early to speak of causalities). Frailty, on the other hand, is associated with decreasing diversity of gut microbes. Where certain negative types (e.g. Eubacterium dolichum and Eggerthella lenta) are elevated. Together with declining species (e.g. Faecalibacterium prausnitzii) they represent a pattern for the susceptibility to frailty to old age [1].

A sedentary lifestyle and an inflammatory circle.

The loss of diversity is caused by age-related, intrinsic and extrinsic factors such as diet, medication, a predominantly sedentary lifestyle and chronic diseases. The microbiome changes damage the intestinal balance and create a pro-inflammatory environment that causes typical signs of aging such as immunosenescence – e.g. an age-related, limited immune response to pathogens. The links between aging and occurring microbial dysbiosis with the typical consequences of intestinal permeability, inflammation and decline in immune function can serve as a therapeutic approach to reverse the immune-aging-clock and possibly support overall good health in advanced age [2]. Studies have shown that the diversity of bacterial species can increase even when you get older [3], or they compensate for a decreasing diversity by growing health-promoting, less dominant species, such as (e.g. Akkermansia, Bifidobacterium, Christensenellaceae). Singh et al. also found that Akkermansia is present in healthy aging [4]. Furthermore, it should be noted that in the 100-year-olds, the microbiome is still dominated by the two strains Firmicutes and Bacteroidetes. In healthy adults, the two strains represent over 80% of all bacterial species. However, the proportions of individual Firmicutes species change. Certain species such as Anaerotruncus colihominis and Eubacterium limosum are then more common and represent a possible pattern of longevity [5]. The microbiome of frail elderly, on the other hand, is dominated by proteobacteria (which, for example, contain the potentially pathogenic Escherichia/Shigella and account for only 16% of the species in healthy adults) and the proportion of Firmicutes and Bacteroidetes decreases. This is due to the fact that in particular the permanent inflammatory reactions that occur more frequently in old age produce reactive oxygen radicals that inactivate strictly anaerobic bacteria such as the firmicutes and favor the proteobacteria, which can tolerate oxygen. This is often observed in older people [6]. Harmful germs such as (Enterobacteriaceae, Enterococcaceae, Staphylococcaceae) thrive in the inflammatory conditions because they are tolerant to the reactive oxygen radicals (ROS) and then continue to promote inflammatory reactions [7].

Prevention should begin between 40-50 years

The microbiome is a dynamic structure that is subject to permanent, profound changes according to the individual phases of life. However, sometimes maladaptations occur, which trigger immune deficiencies or inflammation and in turn have a negative effect on the intestinal community. An inflammatory vicious circle contributes significantly to age-related diseases and frailty [8],[9]. The microbiome should remain relatively stable between 30 and 70 years [10]. However, the prevention of a diverse microbiome in old age should not only begin at 70, but already in middle age between 40 and 50 years.

What can I do?

Osteoporosis

The question arises, what can I do to keep the microbiome intact into old age? The main way to influence the microbiome is nutrition. A plant-based, varied diet and the absence of industrially processed food are the best prerequisites for a healthy microbiome. Now it is also possible to act specifically on the microbiome for prevention. Through the novel mikriobiom-active plant substances, the proteobacteria associated with frailty can be inhibited and at the same time many beneficial bacterial species, such as Akkermansia and Clostridia XIVa [11], increasingly stimulated to grow. In addition, they unfold a high antioxidant or anti-inflammatory effect and can thus break through the inflammatory vicious circle. More precisely, meant are the plant substances naringenin, naringin and apigenin from the group of flavanones, which are found in citrus fruits or tomatoes [12].

In addition, microbiome-active naringenin is effective against osteoporosis, a sign of aging in which more and more bone tissue is broken down. This makes it easier for the bones to break. Osteoporosis is not yet curable. This makes it all the more important to counteract this at an early stage. Otherwise, the bone loss continues to progress. This then means increasing pain and increased bone fractures. Women have almost twice the risk of developing osteoporosis compared to men. The main reason: After menopause, they lack the sex hormone estrogen, which protects the bones. In addition, the bone system in women is naturally "finer" built. Over the age of 50, one in two women suffers a broken bone due to osteoporosis. Between the ages of 50 and 60, at least one in six to seven women (over 15 percent) has osteoporosis. Among the over 70-year-olds, it affects over 45 percent. In both sexes, secondary osteoporosis can also occur as a result of other diseases, even prematurely. Causes are, for example, kidney, liver and intestinal diseases as well as hormone and metabolic diseases. In traditional Chinese medicine, naringenin is used in the Rhizoma drynariae (Gusuibu) against osteoporosis. Naringin and naringenin interact with the estrogen receptor β and thus counteract the reduced activation of the estrogen receptor β during menopause [13]. Rivoira et al. also describe the anabolic effect of naringenin on bones and teeth [14].

Literature

[1] Jackson M., et al. Signatures of early frailty in the gut microbiota. Genome Med. (2016), 8:8. doi: 10.1186/s13073-016-0262-7.

[2] Conway, J. and Duggar, N.A. Ageing of the gut microbiome: potential influences on immune senescence and inflammageing. Ageing Res Rev. (2021),101323. doi: 10.1016/j.arr.2021.101323.

[3] Santoro, A. et al. Gut microbiota changes in the extreme decades of human life: a focus on centenarians. Cell Mol Life Sci. (2018), 75(1): 129–148.

[4] Singh, H. et al. Gastro-intestinal and oral microbiome signatures associated with healthy aging. Geroscience (2019);41(6):907-921. doi: 10.1007/s11357-019-00098-8. 

[5] Biagi E. et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One (2010), 5(5):e10667. doi: 10.1371/journal.pone.0010667.

[6] Candela M., et al. Maintenance of a healthy trajectory of the intestinal microbiome during aging: a dietary approach. Mech Ageing Dev. 2014;136–137:70–75. doi: 10.1016/j.mad.2013.12.004.

[7] Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. (2009), 9:313–323. doi: 10.1038/nri2515.

[8] Woodmansey EJ. Intestinal bacteria and ageing. J Appl Microbiol. (2007);102: 1178–1186. doi: 10.1111/j.1365-2672.2007.03400.x.

[9] Buford TW. (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome. (2017), 5(1):80. doi: 10.1186/s40168-017-0296-0.

[10] Biagi E. et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. (2010); 5(5):e10667.

[11] Kong, F. et al. Identification of gut microbiome signatures associated with longevity provides a promising modulation target for healthy aging. Gut Microbes (2019), 10(2): 210–215.

[12] Fidélix, M. et al. Microbiota modulation and effects on metabolic biomarkers by orange juice: a controlled clinical trial J Agric Food Chem. 2020 Nov 11;68(45):12651-12660.  doi:

[13] Guo, D. et al. Double directional adjusting estrogenic effect of naringin from Rhizoma drynariae (Gusuibu). J Ethnopharmacol. (2011), 138(2):451-7. doi: 10.1016/j.jep.2011.09.034.

[14] Rivoira, M. A., et al. New Perspectives in the Pharmacological Potential of Naringin in Medicine. Current Medicinal Chemistry (2020), DOI: 10.2174/0929867327666200604171351

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