The Microbiota and Optimal Longevity: History and Mechanisms

Without optimal microbiota diversity and specificity, there can be no healthy and long life extension  among mammals, let alone 120-150 years human lifespans. In this blog-article, I will briefly review the history and the state of Microbiota-Gerontology research. (Section A) After identifying a few mechanisms that help explain the inner workings of the microbiota’s healing factory (Section B), I will briefly examine a few microbiota-based optimal longevity protocols. But i will do this in another blog.

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Top: Bifidobacterium adolescentis (gram, Creative communs 3.0)

Section A

The History of the Microbiota & Longevity Research

Diverse cultures and traditions have intuitively known for millennia that cultured bacteria-laden food, called probiotics, helps not only to preserve food, but also promotes the nurturing and the balance of the human gut. In this realm, the history of probiotics can be traced to the first use of cheese, wine and other fermented products during the time of the ancient Greeks and Romans. (1)

It took many centuries to identify the mechanisms that help to explain probiotics benefits. At the end of the 19th century, Nobel prize winner Ilia Metchnikoff was the first to put some of these gut bacteria to the scientific test. Once completed, his research suggested that humans could live significantly longer and healthier if they consume beneficial bacteria. (2)

In order to find the beneficial bacteria in yogurts, Metchnikoff isolated several strains of lactobacilli, which he called Lactobacillus bulgaricus. He proved beyond any reasonble doubt that it is possible to make eatable fermented milk products using pure cultures of L. bulgaricus. Furthermore, according to Metchnikoff’s hypothesis, lactobacilli were eliminating pathogenic toxin- producing bacteria from the colon, thanks to which human lifespan could be extended.  (3)

Interested in Metchnikoff’s work, Louis Pasteur invited him to his new Institute (l’Institut Pasteur) in Paris (1888) to pursue his research. The Russian-Ukrain scientist was appointed the Institute’s Director of Morphological Microbiology, and remained there until his death in 1916, 8 years after having won a Nobel Prize for his research on the microbiota and phagocytosis. (4)

Fast forwarding a few decades, despite multiple successes with probiotics as a healing substance, the era of money-making pharmaceutical drugs and antibiotics came and wiped out probiotics as a safe and efficient healing technique of modern medicine. To this day, the FDA will still harasses any company who makes any probiotic health claim. For example, not too long ago, the European Yogurt  company Dannon got sued in the United States and fined over 20 millions dollars for having made such health claims. (5) (Source)

However, with the growing epidemics in chronic diseases and the Mrsa superbugs that come with the administration of antibiotics, inter alia, today, probiotics research has started to proliferate. To such an extent, that in 2008, the Human Microbiome Project was unleashed. On 13 June 2012, a major milestone of the Human Microbiome Project (HMP) was announced by the NIH director Francis Collins, including on the microbiome’s genome, (6), over 2 million microbiota genes that surpass by far human eukariotic genes by over 100 times.

The announcement was accompanied with a series of coordinated articles published in Nature. (7)  In this perspective, the research for healthy aging via microbiota intervention has intensified. (8) Including with comparative human microbiota analyses between rural villages (where many longevity zones are housed) versus stressed and toxemia-exposed megapolises. (9)

Section B

Mechanisms & Causation

Disharmony in the composition, diversity and balance of mammalian intestinal microbiota, what is called dysbiosis, has been increasingly researched. These deleterious microbiota alterations are mostly caused by unhealthy eating habits, toxemia from the environment, chronic stress from our culture models, circadian mishaps, infections, pathogens, age-related oxidative stress and holistic lifestyle deficiencies. Once dysbiosis gets durably fixed in one’s gut, the body’s immune system tends to weaken. With an impaired immuno-surveillance system, the body can’t efficiently fight off pathogens and preserve a balanced microbiota. As a consequence, a low-grade chronic inflammation condition ensues, that which favors chronic diseases, accelerated aging and more dysbiosis of the gut.

In this perspective, Metchnikoff had discovered one of the mechanisms that these probiotics use to boost life (chi, vitality, immunity). To this end, he had observed that some probiotic bacteria could swallow other undesirable bacteria, microbes, yeast, molds and even toxins and destroy them, thereby preventing them from causing excessive damage to the body.  He called this process  ‘phagocytosis’. He also showed that this process is part of the immune response to nefarious antigen invasion. One year before he was awarded a Nobel prize in physiology, Élie Metchnikoff, in 1907, hypothesized that it should be possible to  concretely modify the gut flora and to replace harmful microbes with useful microbes. (10)

Metchnikoff, at that time a professor at the Pasteur Institute in Paris, proposed another hypothesis, related to this bacterial phagocytosis process. In this perspective, he proposed that the aging process results from the activity of putrefactive (proteolytic) microbes producing toxic substances in the large bowel. Proteolytic bacteria such as clostridia, which are part of the normal gut flora, produce toxic substances including phenols, indols, and ammonia from the digestion of proteins. According to Metchnikoff, these compounds were responsible for what he called “intestinal autointoxication”, which would cause the physical changes associated with old age. (11)

It was at that time known that milk fermented with lactic-acid bacteria inhibits the growth of proteolytic bacteria because of the low pH produced by the fermentation of lactose. Metchnikoff had also observed that certain rural populations in Europe, for example in Bulgaria and the Russian steppes, who lived largely on milk fermented by lactic-acid bacteria were exceptionally long lived.

Based on these observations, Metchnikoff proposed that consumption of fermented milk would “seed” the intestine with harmless lactic-acid bacteria and decrease the intestinal pH, and that this would suppress the growth of proteolytic bacteria.

Metchnikoff himself introduced in his diet sour milk fermented with the bacteria he called “Bulgarian Bacillus” and believed his health benefited. Friends in Paris soon followed his example and French physicians began prescribing not only wine (in moderation), but also “lait caillé” (aka kéfir, sour cream and sour milk) for their patients. (12)

While lactobaccilus (LAB) was Metchnikoff’s “enfant chéri”, bifidobacteria was a Pasteur Institute colleague, Henry Tissier’s focus. Tissier first isolated this bacteria from a breast-fed infant. The isolated bacterium named Bacillus bifidus communis was later reclassified to the genus Bifidobacterium. Tissier found that bifidobacteria are dominant in the gut flora of breast-fed babies and he observed clinical benefits from treating diarrhea in infants with bifidobacteria. (13).  Like with Metchnikoff’s experiments, Tissier showed that by introducing a beneficial bacteria within the guts of diarrhea children, that there followed a bifidobacterial displacement of proteolytic bacteria that was causing the disease, a displacement that weakened or neutralized its virulence.

At Institut Pasteur, with both the French team and Professor Metchnikoff, a credible theory on the microbiota and health was established, including on the aging process.

“Metchnikoff made the assumption that aging was probably due to the poisoning of the body by pathogenic micro-organisms in the large intestine,” says Michel Morange, the Director of the Cavaillès Centre for the History and Philosophy of Science at France’s Ecole Normale Supérieure. “[Metchnikoff] consequently recommended a specific way of eating, which was intended to change the microbial population in the large intestine, and so avoid poisoning.” (14) (Source)

In addition to this above mentioned bacterial displacement mechanism, today, Research has identified five other mechanisms that help to explain why probiotics and a balanced diversified microbiota are medically vital. a). Probiotics bind to adhesion sites, preventing pathogen attachment by reducing the surface area available for pathogen colonization. b). Probiotics generate signals to immune cells thanks to which the secretion of cytokines are produced, that which targets the pathogen for destruction. c). Probiotics attack pathogenic organisms by releasing bacteriocins, killing them directly. d). Probiotics compete against pathogens for the same essential nutrients, leaving less available for the pathogen to utilize. (15) e). Microbiota resiliency, diversity, balance and their micro-environment helps to thwart the inflammatory malignancy process. When microbiota barriers are breached, invasive microbes can elicit proinflammatory and immunosuppressive programs through various pathways, including, but not limited to cancer-associated microbes that activate NF-κΒ signaling within the tumor microenviroment. (16) (Source)

Discussion

Metchnikoff’s Theory, which won him the Nobel Prize for Physiology (Medicine) in 1908, along with Paul Ehrlich from Germany, was a scientific breakthrough. Metchnikoff believed that certain lactic ferments and probiotics could combat the harmful effects of certain bacteria in the gut and restore homeostasis, thanks to which it was possible to prolong life.

While not everything that Metchnikoff believed was one hundred percent correct, the gist of his experimentation and research was vitally relevant.  After over one hundred years of medical research, dogma and pharmaceutical imperial reign, (17) today, modern Medicine is staring to use fecal transplants to reverse serious debilitating and age-related diseases, from autism, to obesity and auto-immune disorders.  (Cf blog on diseases and the microbiota).

Conclusion

More and more evidence is mounting each day to show that the human gastrointestinal microbiota plays a key homeostatic role in the normal functioning of physiologic processes that are commonly undermined by aging. Evidence is also accumulating showing that diets and lifestyle significantly shape the composition of the intestinal microbiota. And still more evidence has been established demonstrating how deleterious it is to consume dead, sterile and processed foods that deprive mammalian microbiota from useful environmental genes and homeostatic processes.

Metchnikoff and his colleagues at the Pasteur Institute have cleared the way for a research field that is now booming, and aims to gain a better understanding of the role played by the microbiota and its genes, including, but not limited to trillions of bacteria, viruses and parasites that humans host within the gut.

These one-cell microorganisms we call bacteria that live in animal and human guts are one of the strongest forces of evolution that configured Life to be what it is billions of years ago. (18) Today, the best scientific theory shows that even human mitochondria, the body’s energy factory, were bacteria that got phagocytosed (engulfed) by eukaryotic DNA-nucleus-rich cells a little over 1.4 billion years ago in order to form a symbiotic relationship for the benefit of Life. (Source).  They are a key player in human Evolution, Life and health. Zapping these so called “bad” bacteria with antibiotics, chlorine and the likes is like killing the good and bad cancer cells with cytotoxic chemotherapy and radiation and akin to the bombing of entire cities and their civil population in order to kill a few bad guys.

With stem cell biology and telomere science, microbiota medicine is one of the key new disciplines that will hopefully spur today’s contemporary medicine’s experts to change  their present symptomatolgy based medical paradigm. Based on “Kill the symptom”  and  “One pill for each ill” approaches, this paradigm has never respected the microbiota’s integrity, let alone naturopathic principlesWhile ok for acute or emergency care, today’s allopathic medical model is largely responsible for the chronic disease epidemics and the short human lifespans we are witnessing. In another blog, I will show both the safety and the efficiency of microbiota medicine for multiple chronic diseases including with regard to the aging process.

Christian Joubert (HMI director and cso)

Reference Notes

(1). Gismondo MR, Drago L, Lombardi A (1999). “Review of probiotics available to modify gastrointestinal flora”. Int. J. Antimicrob. Agents. 12 (4): 287–92. In the ancient world, fermented foods were often considered to have mystical and sacred powers because of their health benefits and life-extending properties, from fermented cacao beans, to fermented grapes (wine), teas and different herbs, natto, kimchi and other foods.
(2). Metchnikoff E. 1908. The prolongation of the life. Optimistic study. G.P. Putnam’s sons, New York and London. Podolsky SH. 2012. Metchnikoff and the microbiome. Lancet 380:1810–1811. Metchnikoff noticed the correlation between the longevity of Bulgarian shepherds and their yogurt.
(3). https://medium.com/@Danone/one-yogurt-100-years-of-science-34d353037cf4 Metchnikoff was not only the first to study bacteria in fermented milk; he also promoted production of the first bacterial drug, Lactobacillin, which was manufactured in 1912.
(4). Ibid  His collaborators at the Pasteur Institute were also the first to perform experiments on germ-free animals, starting gnotobiology as a new branch of biological science. The ‘Pasteur Institute Collection’ has a library of strains (the name given to a line of identical bacteria or viruses) created by doctor and biologist Jean Binot at the end of the 19th Century, now contains over 12,000 strains of different bacteria. These  micro-organisms are frozen via lyophilisation with a view to preserving biodiversity.
5). https://medium.com/@Danone/one-yogurt-100-years-of-science-34d353037cf4
(6) “NIH Human Microbiome Project defines normal bacterial makeup of the body”. NIH News. 13 June 2012.  By mapping the normal microbial make-up of healthy humans using genome sequencing techniques, the researchers of the HMP have created a reference database and the boundaries of normal microbial variation in humans. From 242 healthy U.S. volunteers, more than 5,000 samples were collected from tissues from 15 (men) to 18 (women) body sites such as mouth, nose, skin, lower intestine (stool), and vagina. All the DNA, human and microbial, were analyzed with DNA sequencing machines. The microbial genome data were extracted by identifying the bacterial specific ribosomal RNA, 16S rRNA. The researchers calculated that more than 10,000 microbial species occupy the human ecosystem
(7). Human Microbiome Project Consortium (2012). “A framework for human microbiome research”. Nature. 486 (7402): 215–221. Bibcode :2012Natur.486..215T. PMC 3377744 .  And:  The Human Microbiome Project Consortium (2012). “Structure, function and diversity of the healthy human microbiome”. Nature. 486 (7402): 207–214.
(8). O’Toole PW, Jeffery IB. 2015. Gut microbiota and aging. Science 350:1214–1215.
(9).↵Park SH, Kim KA, Ahn YT, Jeong JJ, Huh CS, Kim DH. 2015. Comparative analysis of gut microbiota in elderly people of urbanized towns and longevity villages. BMC Microbiol 15:49. See also Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. 2009. Bacterial community variation in human body habitats across space and time. Science 326:1694–1697.
(10). His reasoning was   cholera…he actually ingested cholera to test his hypothesis… Élie [Ilya Ilyich] Metchnikoff, 2004 [1907], The prolongation of life: Optimistic studies, p. 116. Springer Classics in Longevity and Aging, New York, NY:Springer, ISBN 0826118771, reprint of 1908 English edition by É.M., same title (P. Chalmers Mitchell, Ed.), New York, NY:Putnam, ISBN 0826118763, itself a translation of 1907 French edition by I.I.M., Essais optimistes, Paris:Heinemann, Retrieved 12 November 2015.
(11). Arteriosclerosis and intestinal poisons. [a contemporary review of Metchnikoff’s work] JAMA 1910, 55:2311-12.
(12). Vaughan RB (July 1965). “The romantic rationalist: A study of Elie Metchnikoff”. Medical History. 9 (3): 201–15. PMC 1033501 .
(13). Tissier, H. 1900. Recherchers sur la flora intestinale normale et pathologique du nourisson. Thesis, University of Paris, Paris, France
(14). https://medium.com/@Danone/one-yogurt-100-years-of-science-34d353037cf4
(15). Bermudez-Brito, M; Plaza-Díaz, J; Muñoz-Quezada, S; Gómez-Llorente, C; Gil, A (2012). “Probiotic mechanisms of action”. Annals of Nutrition and Metabolism. 61 (2): 160–74.
(16). Garrett, WS (3 April 2015). “Cancer and the microbiota”. Science. 348 (6230): 80–6. Cf. See also Gagnière, J; Raisch, J; Veziant, J; Barnich, N; Bonnet, R; Buc, E; Bringer, M. A.; Pezet, D; Bonnet, M (2016). “Gut microbiota imbalance and colorectal cancer”. World Journal of Gastroenterology. 22 (2): 501–518. .
 (17).  While probiotic and prebiotic interventions have been retained by naturopathic medicine, conventional allopathic medicine is now forced to pay attention to what may be one of the body’s most important organ, its microbiota
(18).  Bacteria and archaea are individual single-celled prokaryotes.  According to Science, they are mostly responsible for the orgins of Life on Earth. In the beginning billions of years ago,  Earth was hot, with a lot of  active volcanoes and an atmosphere composed mostly of nitrogen, methane, ammonia, carbon dioxide, and water. There was little if any oxygen in the atmosphere. Archaea and some bacteria evolved in these conditions. Most scientists now suspect that these two groups, bacteria and archaea, diverged from a common ancestor relatively soon after life began. Millions of years after the development of archaea and bacteria, the ancestors of today’s eukaryotes split off from the archaea. So although archaea physically resemble bacteria, they are actually more closely related to us. And they also thrive in human guts. (Source)
Disclaimer: Nothing in this Education Blog should be construed as Medical advise.
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The Happiness Medicine Institute's central mission is centered on shouldering the masses (ie majority of People including, but not limited to the low and modest income categories) to meet their fundamental human birth-right of living a fulfilling, healthy and an evolutionarily designed Lifespan of 120 years and beyond. The only son of a Polish Jew mother and a Catholic Frenchmen father from Bordeaux, Christian and has come to the US, like Lafayette, to share the best of French and European experiences with Americans in order to beat the "enemy". In the 18th century, Lafayette, Rochambeau and France were the decisive forces that toppled those nasty British imperialists in Yorktown, thanks to which American sovereignty was made possible. In the 21st century, the "enemy" is chronic stress and an American food, medical and public health system that is un-necessarily maiming and killing Americans by the millions each year. Once (and if) the official standards of care become consistent with the People's basic needs and with the best Science, then Christian's mission will have been accomplished. In terms of bio, Christian was trained in French conventional medicine, Chinese acupuncture, European naturopathy, law, wine and a few other disciplines. He has partaken in thousands of seminars and conferences to corroborate what the safest, most efficient and cost friendly health restoration and lifespan techniques are. To this end, Christian established a research and education center called happiness medicine institute. A former law professor (Paris and Gonzaga School of Law), organic agriculture farmer (certified by Ecocert), professor of holistic oncology, naturopath and director of other health centers, Christian has been specializing for over twenty years in geroscience and biogerontology as both these "optimal longevity" fields of the Health Sciences are much more "holistic" and useful than conventional medicine insofar as slowing down and reversing age-related pathologies is concerned, including the aging process itself. As a result, by better tweaking the aging process and its concomitant longevity determinants, we can modulate and resolve most chronic diseases, including cancer, auto-immunity, diabetes, mental disorders, cardiovascular events and much more. The only rampant malady holistic medicine is powerless to act upon is arrogance (ie, hubris). Thus, not everyone can benefit from Joubert's expertise. If motivated people comply to a holistic lifestyle with specific longevity and happiness techniques, they can die after having peacefully reached 120 without any chronic diseases. Over 95 percent of chronic diseases are completely avoidable. This claim is not constitutive of what is called a "false promise". The evidence is overwhelmingly established, but most pharmaceutical firms and their medical and political allies ignore these claims and-or are not interested, if only because Joubert's proposed holistic techniques do not generate enough cash-flow for corporate appetite to be satieted. This extension of time to 120 years and beyond will give People more opportunities to better enjoy Life (Joie de vivre) and build the conditions that will lead to a new, lasting, healthier and happier civilization based on the exact opposite values and mechanisms of most of today's outdated and irrational standards and systems. Christian investigates Science, medicine and any other phenomena with medically and legally trained eyes. And digs deep, through multiple layers of knowledge and via multiple fields of science, thank to which he is able to identify the inter-connectiveness of relevant issues and determine the key root cause (or causes) upon which the consultee can act. Thus, over 95 percent of published material and common clinical practice is weeded out in order to get to the “crème”, the quintessence, the clinical pearl or what jurists call the “therapeutic relevance” for the benefit of whatever the health challenge may be….. So don't hesitate to schedule an appointment with Christian before he goes away. By doing so, the consultee will learn innovative, safe, efficient and cost-friendly techniques to achieve a healthy lifespan of over 120 years, as the French Mediterranean lady, Jeanne Calment has, (ie, the book of Guinness confirms she is the longest living human ever and most people don't even know why), as the most successful "bleu zone" does (i.e., the French-cultured Principality of Monaco in the Mediterranean South has the most centenarians, most bleu zoners don't know this) and as the French culture and lifestyle have abundantly shown over the last 1600 years, including, but not limited to its Mediterranean diet, Lourdes, its wine, its thermal medicine as well as to its many other health promoting techniques including France's health-vacation spas and other "joie de vivre" institutions that substantially slow down the rate at which telomeres shorten while significantly upregulating (activating) the other eleven hallmarks of Optimal Longevity. Thus, it's not for nothing that the World Health Organization ranked France as having the best health-care system in the world. To read more on France's health-vacation spas and dozens of validated longevity techniques as well as on Christian’s mission and background, click “about” and examine the website's other links. To benefit in vivo from Christian Joubert’s medical, legal, inter-disciplinary and trans-cultural training and experience, CLICK the Consult LINK in the top menu bar. Thank you.

Posted in Longevity Medicine, Anti-Aging, Gerontology, Telmomeres, Telomerase, Caloric Restriction, mTOR, Sirtuins, Protein Misfoldment

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