The Centenarian Microbiome: What Three Bacteria Reveal About Aging

Researchers have been sequencing the microbiota of centenarians for roughly fifteen years. The earliest studies, conducted in Japan and Sardinia, initially sparked curiosity. Subsequent ones, replicated in China, South Korea, Italy and South America, turned that curiosity into a robust signal. In 2024, a meta-analysis covering eight cohorts of longevous populations from geographically and culturally distinct regions identified microbial signatures shared by individuals who had passed the age of 100 (PubMed).

Two species emerge consistently: Akkermansia muciniphila and Bifidobacterium longum. Their abundance declines with age in the general population. In centenarians, it is maintained or increases. This paradox raises questions about the mechanisms through which these micro-organisms contribute to biological balance over the decades.

The intestinal barrier: the first front of aging

Aging depletes the gut microbiota selectively. Protective species recede. Communication between the microbiota and the immune system loses precision. The best-documented consequence is increased intestinal permeability.

The intestinal mucosa functions as a selective filter. Epithelial cells are connected by tight junctions (claudin-3, ZO-1, occludin) that determine what crosses the wall and what remains in the intestinal lumen. With age, these junctions loosen. Bacterial fragments, particularly lipopolysaccharides (LPS, components of Gram-negative bacterial walls), enter the bloodstream and chronically activate the innate immune system. This process is called metabolic endotoxaemia. It fuels the low-grade systemic inflammation that researchers refer to as inflammaging.

Akkermansia muciniphila acts precisely at this level. Its thermostable surface protein Amuc_1100 binds to TLR2 receptors on epithelial cells and triggers a signalling cascade that stabilises tight junctions (PubMed). It also stimulates colonic mucus production by goblet cells, reinforcing the physical barrier between the microbiota and the epithelium.

The reference clinical trial on this topic remains that of Depommier et al., published in Nature Medicine in 2019. In 32 overweight or obese adults, 12 weeks of supplementation with pasteurised Akkermansia improved insulin sensitivity by 28.6% and reduced fasting insulinaemia by 34% compared with placebo (PubMed).

A more recent result deserves attention. A 2024 randomised double-blind trial in adults over 60 showed that pasteurised Akkermansia improved muscle strength and functional performance (PubMed). The link between the microbiota and muscle function (the gut-muscle axis) is receiving growing attention in geroscience.

Live probiotic, inactivated postbiotic: why form matters

The probiotic/postbiotic distinction is central yet poorly understood. The confusion is maintained by marketing that uses both terms interchangeably. They describe fundamentally different biological realities.

A probiotic is a live micro-organism which, administered in adequate amounts, confers a health benefit on the host. It temporarily colonises the gut, metabolises substrates, and produces active metabolites (short-chain fatty acids, vitamins, antimicrobial peptides).

A postbiotic is an inactivated bacterial cell (by heat treatment, high pressure, or irradiation) whose cellular structures retain their ability to interact with the immune system. Surface components (peptidoglycan, lipoteichoic acid, membrane proteins) remain intact and recognisable by mucosal immune receptors. But the cell does not colonise, does not divide, and does not produce metabolites.

Tyndallisation (named after John Tyndall, a 19th-century physicist) is the most common thermal inactivation process. The temperature is calibrated to destroy cellular activity while preserving surface structures. This is precisely the case with Akkermansia's Amuc_1100 protein, thermostable up to approximately 70 °C, which retains its TLR2 binding capacity after pasteurisation.

This distinction has practical consequences. A postbiotic requires no cold chain. Its immune response is more predictable (no variability linked to colonisation). Its safety profile is enhanced for immunocompromised populations.

Bifidobacterium longum perfectly illustrates this logic. Its tyndallised form (HT-ES1, derived from strain CECT 7347) was evaluated in a double-blind randomised controlled trial involving 200 adults. Over 12 weeks, it significantly reduced the IBS Symptom Severity Score compared with placebo (PubMed). A separate pilot trial in 60 healthy adults showed an increase in butyrate-producing bacteria and a reduction in total and non-HDL cholesterol (PubMed).

What distinguishes B. longum from other bifidobacteria is its influence on the gut-brain axis through tryptophan metabolism and intestinal serotonergic signalling. Preliminary data suggest implications for well-being and sleep quality. The tyndallised form acts here through its wall components (peptidoglycan and lipoteichoic acid) recognised by mucosal TLR2 receptors, exactly as Amuc_1100 does for Akkermansia, but through partially distinct signalling pathways.

The sporebiotics: a transient ally

Bacillus subtilis belongs to a category of its own: sporebiotics. It is the only live probiotic in the trio. Its distinctive feature is the ability to form spores (dormant resistance structures) that survive gastric acidity, bile, and temperature variations. Once in the gut, spores activate and the bacterium resumes metabolic activity.

Its mode of action differs fundamentally from that of postbiotics. B. subtilis is a metabolic transiter. During the several days its intestinal passage lasts, it actively produces:

• digestive enzymes (proteases, lipases, amylases) that facilitate the breakdown of complex nutrients and feed resident bacteria through cross-feeding;
• short-chain fatty acids (butyrate, propionate) that nourish colonocytes (cells of the colonic mucosa) and support intestinal barrier integrity;
• menaquinone-7 (vitamin K2), documented since the foundational research on natto fermentation;
• antimicrobial peptides (subtilisins) that limit the space available to opportunistic bacteria.

A clinical trial in 100 adults over 60 showed that Bacillus subtilis CU1 increased secretory IgA levels (the first line of mucosal immune defence) and reduced the duration of winter respiratory infectious episodes (PubMed). A complementary mechanism was documented in Nature: B. subtilis inhibits Staphylococcus aureus colonisation by interfering with its quorum-sensing system, the communication mechanism bacteria use to coordinate their virulence (PubMed).

More recently, a 2025 double-blind randomised trial in 68 children with antibiotic-associated diarrhoea showed stool normalisation in 93.5% of subjects by day three under B. subtilis HU58, compared with 22.6% on placebo (PubMed).

Three mechanisms, one convergence

The common thread among these three micro-organisms is their action on the intestinal barrier and innate immunity. But they achieve it through complementary pathways.

Akkermansia reinforces tight junctions from the outside, via a thermostable surface protein. Tyndallised B. longum modulates the local immune response through its wall components and influences the gut-brain axis. Live B. subtilis actively produces the metabolites that nourish the ecosystem from within.

Research on the microbiota and longevity is still in its early stages. Cohort studies identify associations, not causation. Clinical trials involve small populations and short durations. No one can claim today that supplementing with Akkermansia extends lifespan. What the data show is that individuals who live the longest in good health share specific microbial signatures, and that these signatures correspond to identified biological mechanisms that are partially reproducible through supplementation. A solid beginning. Not a conclusion.

Frequently asked questions

What is the difference between a probiotic and a postbiotic?#[ + ]

A probiotic is a live micro-organism that temporarily colonises the gut and exerts metabolic activity. A postbiotic is an inactivated bacterial cell (by heat or pressure) whose surface structures retain their ability to interact with the immune system, without colonisation or active metabolism. Both approaches modulate the microbiota, but through distinct mechanisms.

Why use inactivated bacteria rather than live ones?#[ + ]

Tyndallisation (controlled thermal inactivation) preserves cell wall structures (peptidoglycan, lipoteichoic acid, Amuc_1100 protein) that interact with intestinal immune receptors. The advantages include superior stability (no cold chain required), a more predictable immune response (no variability linked to colonisation), and an enhanced safety profile.

Is Akkermansia muciniphila present in everyone?#[ + ]

Yes, Akkermansia colonises the gut from early childhood and normally represents 1 to 4% of the total microbiota. Its abundance decreases with age, excess weight, and certain metabolic disturbances. Centenarians are a notable exception: their microbiota remains enriched in Akkermansia, making it a microbial signature of longevity.

Do the centenarian findings prove a cause-and-effect relationship?#[ + ]

No. Cohort studies show a statistical association, not causation. Centenarians might harbour these bacteria because they are healthy, rather than the other way around. Mendelian randomisation studies are beginning to suggest a potential causal relationship for Akkermansia, but these data remain preliminary.

Does Bacillus subtilis permanently colonise the gut?#[ + ]

No. Bacillus subtilis is a transient micro-organism. Its spores activate in the intestinal tract, exert metabolic activity for several days (producing enzymes, short-chain fatty acids, vitamin K2), and are then naturally eliminated. This distinguishes it from resident probiotics such as lactobacilli.

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References

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4. Kang CH et al. Pasteurized Akkermansia muciniphila HB05 (HB05P) Improves Muscle Strength and Function: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2024;16(24):4370. (PubMed)
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10. Piewngam P et al. Pathogen elimination by probiotic Bacillus via signalling interference. Nature. 2018;562(7728):532-537. (PubMed)
11. Sorensen K et al. Effects of spore-forming probiotic Bacillus subtilis HU58 in children with antibiotic-associated diarrhoea. Beneficial Microbes. 2025;16(3):1-10. (PubMed)
12. Martorell P et al. Heat-Treated Bifidobacterium longum CECT-7347: A Whole-Cell Postbiotic with Antioxidant, Anti-Inflammatory, and Gut-Barrier Protection Properties. Antioxidants. 2021;10(4):536. (PubMed)