The Gut, Diseases and Optimal Longevity

In this blog-article, i will first look at the evidence that shows that most mainstream elders’ microbiota are characterized by dysbiosis and gut imbalances, both of which are correlated with different types of diseases. (Section A) Thereafter, I will invoke evidence that shows  that elders and even super-centenarians who have a healthy lifestyle have a different microbiota composition and way fewer diseases, if any. (Section B)

 Section A

Mainstream Elders’ Microbiota and Dysbiosis

The gut microbiota (GM) is a complex, evolutionarily molded ecological system, which contributes to a variety of physiological functions. The GM is highly dynamic, being sensitive to environmental stimuli, and its composition changes over the host’s entire lifespan. At the end of most elders’ life, especially mainstream elders, the evidence shows that the composition of their microbiota is considerably different from that of younger adults and characterized by dysbiosis, lack of diversity and imbalances. Below, a few pieces of supporting material.

“We conclude that increasing biological age in community-dwelling adults is associated with gastrointestinal dysbiosis.” (1)

“In this issue of Cell Host & Microbe, Thevaranjan et al. (2017) reveal that heightened inflammation is associated with deregulation of homeostatic interactions between intestinal microbes and the aging host”. (2) (Source)

 “These changes suggest that changes in the gut microbiota and associated increases in gut permeability and peripheral inflammation may be important mediators of the impairments in behavioural, affective and cognitive functions seen in ageing.” (3)

In terms of microbiota composition, a low abundance of phylum Firmicutes and an overall low diversity were detected in elderly subjects in mutliple studies. (4) Low diversity has been found to associate with increased health risks. (5)  Another study has reported significantly higher abundance of Bacteroidetes, and lower abundance of Clostridium cluster IV in elders compared to younger subjects.(6)

 Section B

Healthy Elders and Supercentenarians benefit from strong diversified microbiota

In a study published by Current Biology on June 6th 2016, (7) Scientists analyzed the gut microbiota of a number of different populations: adults (aged 22-48), older people (65-75), centenarians (99-104) and super-centenarians (105-109). The results were as follows. First they found that the older the people in these cohorts got, the more  symbiotic, beneficial bacteria diminish in favor of unhealthy bacteria. Next these scientists discovered that super-centenarians microbiota was different, benefiting from a healthy balance microbiome with three species of bacteria being relatively robust.

“Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangement in their co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly support health maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae”. (7) (Source)

In the super-centenarian group, these last three species were a well developed subgroup. Multiple health benefits were associated with these bacterial species.

“Together with Akkermansia  and Bifidobacterium, well-known health-associated genera whose abundance and/or prevalence interestingly increased in semi-supercentenarians, known to promote immunomodulation, protect against inflammation, and promote a healthy metabolic homeostasis”. (Source)

To which was added the bacterial group Christensenellaceae was added.

Christensenellaceae  might represent a signature of the ecosystem of extremely longevous people (….) whose abundance is the most significantly influenced by host genetics suggesting an interesting possible link to the heritable component of human longevity”. (Source).

Below, more detailed focus on these three bacterial groups

Akkermansia muciniphila

Akkermansia muciniphila is a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval-shaped mucin-degrading bacterium. (8) Its genus, Akkermansia, was proposed in 2004 by Muriel Derrien and others. (9) This genus is part of the family called Verrucomicrobiaceae which is part of the Order called Verrucomicrobiales, which is part of the class named Verrucomicrobiae. Apparently, this class appears to have only  one species. ((Source)

This mucin-degrading bacterium has been recently shown to have direct association with an optimal metabolic and mucus lining status. The more this bacteria thrive and reproduced, the better were inflammatory markers, lipid synthesis, several markers of diabetes and even risks of cardiovascular disease. (10)

Researchers concluded that this species of bacteria maintained healthy metabolism, and prevented weight gain and development of fatty tissue (11).  To test the safety and efficiency of this species of bacteria,  Scientists put this bacterium to the test by administering  this species to people with low levels. As a result, there was a decrease in inflammation, lipid markers as well as improvements in blood sugar levels (12).

In this realm, studies have shown an inverse relationships between A. muciniphila colonization and inflammatory conditions such as appendicitis or irritable bowel syndrome (IBS). In one study, reduced levels of A. muciniphila correlated with increased severity of appendicitis. In a separate study, IBS patients were found to have lower levels A. muciniphila in their intestinal tract than individuals without IBS. (13).

Researchers have discovered that A. muciniphila may be able to be used to combat obesity and type 2 diabetes. The study was carried out with mice, overfed to contain three times more fat than its lean cousin. The obese mice were then fed the bacteria, which were shown to reduce the fat burden of the mice by half without any change to the mice’s diet.

Still in this perspective, a study published in June 2015 showed an association between the abundance of A. muciniphila and healthier metabolic status in overweight/obese adults, including insulin sensitivity. The healthier subjects were those with high A. muciniphila abundance and gut microbial richness. In addition, this study showed that having higher abundance of A. muciniphila at baseline was associated with greater clinical benefits after weight loss. (14)

In August 2015, additional research demonstrated that dietary fats influence the growth of Akkermansia muciniphilia relative to other bacterium in the dietary tract. Researchers conducted a study in which mice were fed diets which varied in fat composition but were otherwise identical; one group received lard while the other received fish oil. After 11 weeks, the group receiving a fish oil diet had increased levels of A. muciniphila and bacterium of genus Lactobacillus, while the group receiving a lard diet had decreased levels of A. muciniphila and Lactobacillus. Additional testing was performed by conducting fecal transplants from mice on the fish oil diet or the lard based diet into a new group of mice which had their native gut flora eradicated with antibiotics. All of these mice were then fed a lard based diet. Despite receiving the same lard-based diet for 3 weeks, recipients of transplants from lard-fed donor mice showed increased levels of Lactobacillus and increased levels of inflammation, while recipients of transplants from fish oil-fed donors showed increased levels of A. muciniphila and decreased levels of inflammation. Researchers concluded that the increase in A. muciniphila corresponded to a reduction in inflammation, indicating a link between dietary fats, gut flora composition, and inflammation levels. (16)

Given the present difficulty to find this species in the supplement market, it has been shown that a diet rich in omega-3 increases levels of Akkermansia muciniphila in the gut. (17) There are other ways to increase this species, see the Blog-article devoted to this species. (Source) This bacterium is naturally present in the human digestive tract at from 1 to 5%, but gets depleted with a non holistic lifestyle and deviant aging, one consequence of which is an acceleration of senescence, if only because of this species’ important role in keeping the mucus lining of the colon in good shape. (Source)


Christensenella is a genus of Gram-negative, nonspore-forming, anaerobic, and nonmotile bacteria from the family Christensenellaceae. Phylum: Firmicutes: Class: Clostridia. Order: Clostridiales. Family Christensenellaceae. Genus: Christensenella. This Genus has three species C. massiliensisC. minuta, C. timonensis, all of which have been isolated from human faeces. (18)

Christensenella massiliensis’ discovery is quite recent. (19)  Christensenella timonensis also. (20)   C. minuta has been know for longer. It has been associated with  adiposity. (21) In addition, this bacterium impacts weight control, an important longevity and general health biomarker. In a test on 977 volunteers, humans with higher levels of Christensenella in their guts were found to be more likely to have a lower body mass index than those with low levels. (22). Interestingly, it has been suggested that the more one exercises, the more these bacteria flourish in one’s gut flora (23)

However, it may be a prerequisite to first have this bacterial group within the gut, as the evidence suggests that these microbial critters may be inherited, (24) either directly or via the baby’s bacterial immersion from his-her mother (i.e., breastfeeding and vaginal canal birth). (25)


Bifidobacterium is a genus of gram-positive, nonmotile, often branched anaerobic bacteria. These unicellular bacteria are ubiquitous inhabitants of the gastrointestinal tract, vagina and mouth (B. dentium) of mammals, including humans. Bifidobacteria are one of the major genera of bacteria that make up the colon flora in mammals. Some bifidobacteria are used as probiotics. Before the 1960s, Bifidobacterium species were collectively referred to as “Lactobacillus bifidus”. (26) In 1899, Henry Tissier, a French pediatrician at the Pasteur Institute in Paris, isolated a bacterium characterised by a Y-shaped morphology (“bifid”) in the intestinal flora of breast-fed infants and named it “bifidus”. (27) This would appear to be the starting point of bifidobacterium’s scientific existence.

What Are Bifidobacteria?

Bifidobacteria are y-shaped bacteria found in your intestines, and they’re incredibly important for your health.

Researchers have discovered nearly 50 species of these beneficial bacteria, each of which is thought to have different functions and health benefits (10).

Despite their huge importance for the body, Bifidobacteria typically make up less than 10% of the bacteria in the adult gut microbiome (11).

One of the main functions of this type of bacteria in humans is to digest fiber and other complex carbs your body can’t digest on its own (12).

Fiber has been shown to help reduce weight gain and the risk of diabetes, heart disease and other chronic disorders. Bifidobacteria may help reduce the risk of these diseases by digesting fiber (12, 13).

That’s because when they digest fiber, these beneficial bacteria produce important chemicals called short-chain fatty acids (SCFAs). These compounds play a number of important roles for gut health, and may also help control hunger (14, 15).

Bifidobacteria help produce other important chemicals too, including B vitamins and healthy fatty acids (16, 17).

They may also help prevent infections from other bacteria such as E. coli, in part by producing chemicals that prevent toxins from passing into the blood (18).

Because these bacteria are important for health, they’re often used as probiotics in supplements or certain foods. Probiotics are live microorganisms that provide a specific health benefit when consumed.


Bifidobacteria are healthy bacteria found in your intestines that help digest fiber, prevent infections and produce important healthy chemicals.






Bifidobacteria May Help Prevent Certain Diseases

Many diseases are associated with low numbers of Bifidobacteria in the intestines.

For example, studies have shown that people with celiac disease, obesity, diabetes, allergic asthma and dermatitis all appear to have lower levels of Bifidobacteria in their intestines compared to healthy people (25, 26, 27).

For this reason, a number of studies have examined whether taking Bifidobacteria in the form of probiotic supplements can increase their abundance in the gut and improve disease symptoms.

Certain species may help improve symptoms of irritable bowel syndrome (IBS), including bloating, cramps and abdominal pain.

A large study of 362 people found that taking a Bifidobacteria probiotic for four weeks significantly improved symptoms of IBS (28).

Other studies found that the same Bifidobacteria probiotic also reduced inflammation in people with inflammatory bowel disease, ulcerative colitis, chronic fatigue syndrome and psoriasis (29, 30).

This crucial strain of bacteria may help improve other health markers too. One study found that taking a Bifidobacteria probiotic for 45 days reduced body mass index (BMI) and blood cholesterol in people with metabolic syndrome (31).

Studies have found similar positive effects for lowering cholesterol (32).

Interestingly, Bifidobacteria probiotics may even help brain health.

Two studies have shown that, in combination with other probiotics, Bifidobacteriareduced psychological distress and negative thoughts associated with sad mood in healthy people (33, 34).

Furthermore, one recent study was the first to show that probiotics may benefit people with depression.

One study investigated the effects of a Bifidobacteria probiotic in 44 people with IBS and mild-to-moderate depression. Those who took the probiotic had significantly lower depression scores than those who took the placebo (35).



A number of diseases are associated with reduced levels of Bifidobacteria in the intestines. Supplements of the bacteria may help treat IBS, high cholesterol and even mental health disorders.


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How to Increase Bifidobacteria in Your Gut

Increasing the amount of Bifidobacteria in your intestines may help prevent or treat symptoms of various diseases.

Here are a few ways you can help them grow:

Take probiotics: Consuming Bifidobacteria probiotics can increase their numbers in your intestines.

Eat high-fiber foods: These beneficial bacteria can break down fiber. Therefore, foods rich in fiber, such as apples, artichokes, blueberries, almonds and pistachios, can all help your Bifidobacteria thrive (36, 37, 38).

Eat prebiotic foods: Not to be confused with probiotics, prebiotics are carbs that help healthy bacteria grow. Onions, garlic, bananas and other fruit and veggies all contain prebiotics that can increase Bifidobacteria (39, 40).

Eat polyphenols: Polyphenols are plant compounds that can be broken down by gut bacteria. Polyphenols from foods such as cocoa, green tea and red wine all increase Bifidobacteria in the gut (41, 42).

Eat whole grains: Whole grains such as oats and barley are very good for gut health and can help increase intestinal Bifidobacteria (43, 44).

Eat fermented foods: Fermented foods such as yogurt and kimchi contain healthy bacteria. They mainly contain Lactobacilli, but sometimes also contain Bifidobacteria, and help increase them in the gut (45).

Exercise: Some studies in mice have suggested that exercise may increase Bifidobacteria. Women who exercise more also tend to have more of the bacteria, but this may be due to other factors, like a healthy diet (46, 47).

Breastfeed: If you can, consider breastfeeding your baby to increase his or her Bifidobacteria. Breastfed babies tend to have more of the bacteria than those who are bottle-fed (23).

Choose vaginal birth, when possible: Babies born by standard vaginal delivery have more Bifidobacteria than those born by C-section (24).


You can increase Bifidobacteria by eating fiber-rich foods such as fruit, vegetables and whole grains. You can also take probiotics that contain the bacteria.


Bifidobacteria — Powerful Probiotic Protection

Bifidobacteria are one of the most popular and best-studied probiotic organisms. The bifidobacteria are a large group of normal intestinal organisms with a host of overlapping benefits.

Bifidobacteria probiotics have long been used as dietary supplements in Japan, to achieve and maintain high levels of healthy bifidobacteria in the colon. Breastfed infants develop a simple microbial population dominated by bifidobacteria, helping the growing child to fend off multiple challenges to the immune system.50 As we age, the numbers of bifidobacteria in our intestines drop, while less beneficial and more harmful organisms multiply. Experts now recommend high bifidobacteria levels at all ages.50 Supplementing with bifidobacteria produces a wide range of health benefits. Bifidobacteria supplements are shown to raise protective HDL cholesterol levels in humans and animals, and lower total and LDL cholesterol levels.37,51-53 The corresponding reduction in the ratio of LDL to HDL cholesterol represents an important reduction in cardiovascular disease risk.

Bifidobacteria supplementation also suppressed inflammatory cytokine production by the intestines of elderly volunteers, reducing the burden of inflammation that contributes to cardiovascular, cancer, and metabolic disease risk, and thereby early death.54 Intriguingly, animal studies demonstrated a significant increase in longevity in supplemented mice.55 Similar studies in humans are eagerly awaited, offering as they do a means for selecting specific probioticsto prolong human lifespans.56

The most prominent effects of bifidobacteria supplementation are on the health of the intestinal tract itself. Supplementation reduced episodes of acute diarrhea by 34%, and those of antibiotic-associated diarrhea (a major cause of illness and death in older people) by 52%, while reducing traveler’s diarrhea episodes by 8%.57 Bifidobacteria supplementation for two weeks also shows promise in improving diarrheal illness in people with lactose intolerance.58

People with irritable bowel syndrome suffer from alternating bouts of diarrhea and constipation, often suffering painful abdominal bloating and gas production. Bifidobacteria supplementation produced a significant reduction in abdominal distension and improved symptom scores along with faster bowel transit times (which reduces cancer risk).59,60

Many people have frequent minor digestive symptoms such as bloating, gas, and periodic constipation, all of which, while not dangerous, appreciably reduce comfort and quality of life. Several recent studies demonstrate significant improvements in measures of gastrointestinal wellbeing, decreases in digestive symptom scores and bloating, and increases in health related quality of life during bifidobacteria supplementation.61,62

The much more dangerous inflammatory bowel diseases ulcerative colitis and Crohn’s disease are the source of untold misery and a major risk for colon cancer. Because of their ability to fight inflammation, bifidobacteria supplements have received special attention in managing these conditions.26

Bifidobacteria supplements enhance the “tight junctions” between intestinal cells that allow leakage of dangerous organisms and their products into the bloodstream in ulcerative colitis.63 They also alter the intestinal environment, making it unfavorable for organisms that trigger episodes of colitis.64 Clinical studies show marked improvements in symptoms of inflammatory bowel diseases with bifidobacteria supplements.65-67

Bowel inflammation is a major risk for colon cancer, the third most common cancer in the world. Bifidobacteria supplementation lowers levels of a number of biological markers of colon cancer risk in patients with colitis.68 It also blocks development of new tumors in an animal model of toxin-induced colon cancer.28 More definitive human studies remain to be conducted, but indications are bright for bifidobacteria as potent cancer-preventing pharmabiotic agents.



There are many strains of beneficial bifidobacteria, all of which have related, overlapping benefits. One challenge to development of effective supplements has been to keep cultures of the organism stable, and to deliver them alive to the colon after surviving the extreme conditions of the stomach and small intestine.69

A strain of bifidobacteria, called BB536®, appears to meet that challenge, and to have unique benefits throughout the body.

The BB536® strain of bifidobacterium logum has been shown to increase the numbers of bifidobacteria living in the colon.69,70 That increase allows BB536® cultures to produce marked effects on intestinal, and whole body, immune responses, with potentially far-reaching impact.

BB536® has been most extensively studied in Japan, where subjects with reactions to cedar pollen experience typical allergic symptoms of sneezing, runny nose, and itchy eyes. This condition, Japanese cedar polinosis, is far from deadly, but offers insight into the ability of BB536® to modulate immune responses by multiple pathways.

This strain BB536® reduces production of the special antibody, IgE, which is produced in response to allergens, parasitic infections, and certain other common human conditions.71 BB536® also suppress cellular immune responses that contribute to allergic symptoms and inflammation.72 Finally, BB536® reduces production of inflammatory cytokines that closely correlate with symptom development.73,74

Human studies with BB536® repeatedly demonstrate its ability to alleviate allergic symptoms of Japanese cedar polinosis, with decreases in runny nose, nasal congestion, eye symptoms, and composite symptom scores.75,76

While BB536® suppresses overactive immune responses in allergic patients, exciting new studies are showing that it can enhance the immune response to infections.

In older adults, BB536® reduced the incidence of influenza infection and fever in one at-risk population, compared with placebo recipients.77 Flu symptoms and death from influenza are largely caused by excessive inflammatory responses. An example of excess inflammatory response is pneumonia that can be induced by influenza viruses. These excessive inflammatory responses were reduced in animals exposed to influenza virus that were supplemented with BB536®.78

Studies show that BB536® can prevent infection with the deadly Pseudomonas organism in mice with weakened immune systems.79 And humans who supplemented with BB536® showed a reduction in numbers of a dangerous strain of the bacterium Bacteroides fragilis in their intestines.80

BB536® may also reduce cardiovascular risk factors, though data are preliminary to date. Supplements were effective at lowering plasma LDL cholesterol in women with elevated lipid levels in an early trial.81


Age and the modern environment pose grave threats to the balance of favorable organisms in your intestine indicating a benefit to those who supplement with healthy probiotic cultures. The bifidobacteria are an especially active group of probiotic organisms, with beneficial effects on the immune system and chronic disease.

Bifidobacterium Subtili

In addition, elder in Asia

Microb Cell. 2017 Apr 3; 4(4): 133–136.

Published online 2017 Mar 16. doi:  10.15698/mic2017.04.569

 We found that biofilm-proficient B. subtilis colonized the C. elegans gut and extended the worm lifespan significantly longer than did biofilm-deficient isogenic strains. In addition to biofilm proficiency, the quorum-sensing pentapeptide CSF and nitric oxide (NO) represent the entire B. subtilis repertoire responsible for the extended longevity of C. elegans. B. subtilis grown under biofilm-supporting conditions synthesized higher levels of NO and CSF than under planktonic growth conditions, emphasizing the key role of the biofilm in slowing host aging. Significantly, the prolongevity effect of B. subtilis was primarily due to a downregulation of the insulin-like signaling system that precisely is a key partaker in the healthy longevity of human centenarians. These findings open the possibility to test if the regular consumption of B. subtilis incorporated in foods and beverages could significantly extend human life expectancy and contribute to stop the development of age-related diseases.

Resists Harmful Organism Overgrowth

Studies have shown that this probiotic can produce compounds that are naturally disruptive to harmful organisms. In essence, Bacillus subtilis helps displace unfriendly organisms in the body by affecting their ability to colonize.[5]

Supports Enzyme Production

Enzymes and probiotics have a symbiotic relationship. Both are critical for digestive and gastrointestinal health. Individually, not only do enzymes promote intestinal integrity, they help create an environment that’s favorable to probiotic bacteria.[6] In turn, Bacillus subtilis supports the production of beneficial enzymes in the gut, including amylase, protease, pullulanase, chitinase, xylanase, and lipase.

Tamehiro, Norimasa, et al. “Bacilysocin, a Novel Phospholipid Antibiotic Produced by Bacillus Subtilis 168.” Antimicrobial Agents and Chemotherapy 46.2 (2002): 315–320.

6Latorre, J.D., Hernandez-velasco, X., Wolfenden, R.E., et al. “Evaluation and Selection of Bacillus Species Based on Enzyme Production, Antimicrobial Activity, and Biofilm Synthesis as Direct-Fed Microbial Candidates for Poultry.” Front Vet Sci. (2016): 95.


Bacteria B. subtilis can form spores –resting cells which are highly resistant- that when they reach the intestine of the host (of the nematode or the human being) germinate making the active bateria form a biofilm on gut mucosa, which is responsible for an increase in the innate immunity of the host, the neuroprotection and the increase in longevity.

“Our study also shows the importance of the gut flora –a group of bacteria that live in the intestine– in people’s health due to its possibility to communicate (quorum sensing) efficiently through the formation of a biofilm with the immune and nervous system of the host”, the researcher states.

Other Health Benefits

Bacillus subtilis offers other incredible health benefits. It may support a healthy immune system, especially in older adults.[7] It also protects the integrity of its DNA—a trait that makes it resistant to mutation.[8] And, perhaps best of all, Bacillus subtilis contributes to a healthy digestive system.[9]

7 Lefevre, Marie, et al. “Probiotic Strain Bacillus Subtilis CU1 Stimulates Immune System of Elderly during Common Infectious Disease Period: A Randomized, Double-Blind Placebo-Controlled Study.” Immunity & Ageing : (2015): 24.

8Lenhart, Justin S., et al. “DNA Repair and Genome Maintenance in Bacillus Subtilis.” Microbiology and Molecular Biology Reviews: (2012): 530–564.

9Khatri, Indu, et al. “Complete Genomes of Bacillus Coagulans S-Lac and Bacillus Subtilis TO-A JPC, Two Phylogenetically Distinct Probiotics.” Ed. Niyaz Ahmed. PLoS ONE 11.6 (2016):

10Kubo, Yuji, et al. “Phylogenetic Analysis of Bacillus Subtilis Strains Applicable to Natto (Fermented Soybean) Production.” Applied and Environmental Microbiology 77.18 (2011): 6463–6469.

†Results may vary. Information and statements made are for education purposes and are not intended to replace the advice of your doctor. Global Healing Center does not dispense medical advice, prescribe, or diagnose illness. The views and nutritional advice expressed by Global Healing Center are not intended to be a substitute for conventional medical service. If you have a severe medical condition or health concern

Bacillus subtilis History and Safety

Originally called Vibrio subtilis by Christian Gottfried Ehrenberg, a prolific German scientist, Bacillus subtilis was given its current name in 1872 by Ferdinand Cohn, a botanist and one of the founders of bacteriology. In the early 20th century, the strain was popular as a natural means for supporting gastrointestinal health. Since then, it has been used in animal feed, probiotic supplements, and food production. Bacillus subtilis is used in Japan and Korea to produce fermented soybean dishes.[10] This bacteria is considered safe and beneficial for human consumption by both the U.S. Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA).

Best Forms of Bacillus subtilis

Bacillus subtilis is readily found in soil—a testament to its ability to withstand environmental stressors. But, that doesn’t mean you need to eat a plate of dirt to introduce Bacillus subtilis to your gut. Some fermented foods, such as natto—a fermented soybean dish that’s popular in Japan—are a source of Bacillus subtilis and other probiotics. Many people find that the easiest and most consistent way to reliably strengthen their gut with Bacillus subtilis is with the help of a trusted, high-quality probiotic supplement.

Global Healing Center has created Floratrex™






A core microbiota accompanies human life, decreasing in abundance along with aging

In longevity, the age-related enrichment of subdominant taxa is boosted

The microbiota of longevous hosts accommodates allochthonous bacteria

“Longevity adaptation” seems to involve enrichment in health-associated gut bacteria





How do probiotic bacteria interact with the host? Bacteria do not live isolated as individual and self-sufficient creatures in nature. On the contrary, bacteria live in natural settings as multicellular and cooperative (social) communities called biofilms or cities of microbes. These biofilms are three-dimensional structured communities of adherent microorganisms encased in a self-produced extracellular matrix, containing networks of channels for nutrient supply and long-distance cell-to-cell communication (quorum sensing, QS) used for division of labor between members of the community

These results directly implicate the probiotic biofilm as the primary cause of the increased lifespan and healthy longevity of C. elegans when fed the probiotic bacterium B. subtilis. This dual microbial-worm interaction would allow the bacterium to colonize and establish a multicellular biofilm in the friendly environment of the worm gut mucosa, a similar scenario to the formation of stable biofilms during the beneficial bacteria-plant interaction of some Bacilli (i.e., B. subtilis and B. amyloliquefaciens) with PGPR (Plant Growth Promoting Rhizobacteria) activity on plant roots (rhizospheric biofilm).


Could probiotic B. subtilis extend human life expectancy? Ranking at the top of human welfare, Japan exhibits the highest world longevity (84 years and 81 years, for female and male, respectively), and home to more than 65,000 centennial persons. Together with a longer longevity, a good quality of life and strong health are desired in elderly people. Japan also exhibits the highest healthy life expectancy (78 years for both sexes at the time of birth). What is the secret of the healthy Japanese longevity? Aging depends on genetic and environmental factors, including dietary habits. In the regular diet of the Japanese population exists the millenarian food called natto (“vegetable cheese”), a natural food that consists of soybean fermented by cells of B. subtilis. Because B. subtilis is the active ingredient of this popular and ancient food, it is tempting to pay attention to this probiotic bacterium, which might naturally contribute to the long and healthy longevity of Japanese people. Taking into consideration that probiotic Bacilli can be incorporated in a daily and safe dose (i.e., 1.0-2.0 x 109 spores/day) in many types of human foods and beverages; the centenarian Metchnikoff hypothesis; and our results, it might be worth investigating whether the regular consumption of probiotic B. subtilis in human food might decrease the rate of aging and detect and stamp out disease because of downregulation of insulin/IGF-1 signaling and enhancement of innate immunity, respectively, at the earliest possible moment. F

How is the prolongevity effect of B. subtilis transduced through the sensory pathways that regulate aging? Lifespan is subject to regulation by conserved signaling pathways and transcription factors that sense stress, environmental cues and nutrient availability. DR and the insulin-like signaling (ILS) pathway are central for the regulation of longevity in different animal models, including C. elegans and humans. These longevity regulatory pathways converge on the positive and negative regulation of the transcription factors DAF-16 (FOXO in humans) and HSF-1, respectively. Significantly, the prolongevity effect of B. subtilis was primarily under DAF-2 (IGF-1 in humans)/DAF-16/HSF-1 control, a finding that links extended lifespan to downregulation of the insulin-like signaling (ILS) pathway. Interestingly, healthy human centenarians likely have IGF-1 receptor genetic variants associated with a slightly reduced functionality of the insulin signaling, an intriguing observation that positively correlates with our results.



The role of probiotics in ageing and longevity

•<li><span itemprop=”datePublished” class=”meta-date”>13 Apr 2016</span> | <span itemprop=”author” class=”meta-author”><a href=”” title=”Posts by Andreu Prados” rel=”author”>Andreu Prados</a></span></li>

•13 APR 2016 | Andreu Prados

Diet, Research & Practice

•Tagged: Ageing Gut Gut microbiota immunity Immunosenescence Inflammation


Over the last decade, the proportion of the developed world’s population over the age of 65 years has inc

reased by more than 10%. Furthermore, it is projected to increase over 20% by 2030. Life expectancy continues to increase globally and is expected to reach the mid-70s by 2050. Maintaining health in older age depends on the appropriate function of the homeostatic systems (nervous, endocrine and immune) and correct interactions between these systems and gut microbiota. However, these systems undergo modifications in elderly persons, thus accounting for a reduction in the functional capacity of all the organs in the body, which, in turn, may evolve toward “inflammaging”, a phenomenon characterized by a low-grade inflammatory state, involved in the aetiology of several age-related chronic pathological conditions. Physiological declines in immune function are termed “immunosenescence”, which may lead to the impairment in both cellular and adaptive immunity, together with age-related oxidative stress, a low-grade inflammatory state, and intestinal dysbiosis. Overall, immunosenescence may be linked to a perturbed gut microbiota and frailty in the elderly.


Gut immune response and microbiota composition are impaired in elderly. In older adults there seems to be a decline in microbiota diversity, with lower numbers of Firmicutes and bifidobacteria and an increase in Bacteroidetes and certain Proteobacteria (which are thought to play a role in bowel disease). However, it is not yet clear how these changes are a result of the senescence of the immune system or altered dietary intake or physical activity.  Despite the fact that ageing has a significant effect on the microbiota, its alterations can be consequent to conditions that occur frequently in the elderly, such as the decline of the general state of health with malnutrition and with increased need for medication. Thus, a causal relationship cannot yet be assumed between aging and gut microbiota changes.


There is therefore a growing awareness about the role of probiotics in modulating the gut microbiota to maintain health in the elderly. Clinical trials that have assessed their effectiveness in ageing populations are scarce, but may show that health benefits can be achieved through: 1) Their effect on the composition of the microbiota in elderly populations; and 2) Their effect on the symptoms of major gastrointestinal diseases. Probiotics with Bifidobacterium and Lactobacillus genera are among the most studied in clinical trials with elderly populations. They may restore a healthy microbiota and control oxidation and inflammatory processes, which can be beneficial in ameliorating immunosenescence, the risk of infections, and nervous system impairments in older adults.


In conclusion, probiotics may have a particular application in elderly populations, especially in terms of protection against infections and perhaps also in the prevention of several age-related diseases. Further studies with a double-blind, placebo-controlled design should be performed for a better assessment of probiotics’ potential to maintain a beneficial microbial balance to promote health in the elderly.


These findings were reviewed in a talk by Dr. Mónica de la Fuente, a researcher from the Faculty of Biology at Complutense University of Madrid during the 7th edition of the latest Spanish Society of Probiotics and Prebiotics (SEPyP)’s annual workshop, which was held on Seville (Spain) on January, 28-29th under the theme: “Probiotics, Prebiotics and Health: Scientific Evidence”.



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Hum Vaccin Immunother. 2012 Jul 1; 8(7): 979–986.

doi:  10.4161/hv.20694

PMCID: PMC3495728

Bacillus subtilis

A temperature resistant and needle free delivery system of immunogens

Hellen Amuguni and Saul Tzipori*

Author information ► Copyright and License information ►

This article has been cited by other articles in PMC.

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Most pathogens enter the body through mucosal surfaces. Mucosal immunization, a non-invasive needle-free route, often stimulates a mucosal immune response that is both effective against mucosal and systemic pathogens. The development of mucosally administered heat-stable vaccines with long shelf life would therefore significantly enhance immunization programs in developing countries by avoiding the need for a cold chain or systemic injections. Currently, recombinant vaccine carriers are being used for antigen delivery. Engineering Bacillus subtilis for use as a non-invasive and heat stable antigen delivery system has proven successful. Bacterial spores protected by multiple layers of protein are known to be robust and resistant to desiccation. Stable constructs have been created by integration into the bacterial chromosome of immunogens. The spore coat has been used as a vehicle for heterologous antigen presentation and protective immunization. Sublingual (SL) and intranasal (IN) routes have recently received attention as delivery routes for therapeutic drugs and vaccines and recent attempts by several investigators, including our group, to develop vaccines that can be delivered intranasally and sublingually have met with a lot of success.

As discussed in this Review, the use of Bacillus subtilis to express antigens that can be administered either intranasally or sublingually is providing new insights in the area of mucosal vaccines. In our work, we evaluated the efficacy of SL and IN immunizations with B. subtilis engineered to express tetanus toxin fragment C (TTFC) in mice and piglets. These bacteria engineered to express heterologous antigen either on the spore surface or within the vegetative cell have been used for oral, IN and SL delivery of antigens. A Bacillus subtilis spore coat protein, CotC was used as a fusion partner to express the tetanus fragment C. B. subtilis spores known to be highly stable and safe are also easy to purify making this spore-based display system a potentially powerful approach for surface expression of antigens. These advances will help to accelerate the development and testing of new mucosal vaccines against many human and animal diseases.

Keywords: Bacillus subtilis, tetanus, vaccine

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Although most vaccines are currently administered systemically, they are less effective against mucosal infections. Ideally, an efficient mucosal vaccine should provide protection not only at the mucosal delivery site but also systemically.1 Mucosal vaccination can induce immune responses both at the mucosal surface usually by producing secretory IgA antibodies and at distant organs through systemic IgG production. The major antibody isotype found at mucosal sites and in external secretions is secretory IgA, predominantly in dimeric form, whereas the principle isotype found in the peripheral blood and in tissue spaces is IgG. A robust mucosal response is manifested by significantly higher fecal IgG and Secretory IgA (sIgA) responses and a mixed Th1/Th2 response as reflected by increased levels of interferon gamma and IL-2 cytokines and a balanced IgG1:IgG2a ratio . SIgA antibodies are considered major effectors in the adaptive immune defense of the mucosal system. More recently, the focus has shifted to mucosal vaccines capable of successfully generating both mucosal and systemic immune responses.2 However, despite decades of extensive research, effective mucosal immunization remains elusive. Our understanding of mucosal immunity and development of mucosal vaccines has faced formidable challenges, with unpredictable results due to complex immune responses.3 The mucosal immune system has also modified itself to thwart invasion and subsequent colonization by harmful microorganisms, to control transmission of pathogens between individuals and to prevent harmful immune reactions against food antigens and commensal bacteria.4 The local microenvironment and the nature and route of antigen delivery are important determinants of the mucosal immune response.2,5 Development of mucosal vaccines capable of effectively inducing both mucosal and systemic immune responses has been the focus of recent studies.2,5 The IN route has been shown to induce strong systemic and secretory antibody responses and requires considerably smaller amount of antigen than would be required for oral administration.6 However, some studies have related retrograde passage of inhaled antigens resulting in neurological side effects.7-9 SL administration has been frequently used to deliver low-molecular-weight


Reference Notes


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Christian is presently working on a new book on Holistic Medicine and Biogerontology, whose content invokes the compelling evidence that supports the following assertion: humans have been genetically designed to live a happy and healthy lifespan to at least 120 years. On this age limit, both evolution-based Science (Cf the Hayflick's limit) and the Bible (Genesis 6:3) concur. The “Joie de Vivre” Vibe that can eradicate today’s chronic disease epidemics and un-necessary suffering is thus within reach. See link on mission for more details.

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