HW functional medicine · 13 min read · 2,513 words

The Aging Microbiome: Gut Health Across the Lifespan

There's an old idea in ecology: the health of any landscape can be read in its soil. Rich soil, diverse life.

By William Le, PA-C

The Aging Microbiome: Gut Health Across the Lifespan

The Garden That Grows You Back

There’s an old idea in ecology: the health of any landscape can be read in its soil. Rich soil, diverse life. Depleted soil, barren land. Your gut microbiome is that soil — and it’s telling a story about how you’re aging.

You carry roughly 38 trillion microbial cells, most of them in the colon. These organisms aren’t passengers. They produce vitamins, train the immune system, regulate inflammation, manufacture neurotransmitters, metabolize hormones, break down fiber into short-chain fatty acids that feed your gut lining, and communicate with every organ system through the gut-brain axis, gut-liver axis, and gut-immune axis. They’re not along for the ride. In many ways, they’re driving.

And with age, the garden changes. Not gently, like autumn. More like a drought.

How the Microbiome Ages

The aging microbiome undergoes characteristic shifts that have been documented across cultures and continents:

Diversity loss. The single most consistent finding. Alpha diversity — the number and evenness of species in a given individual — declines with age. This matters because diversity equals resilience. A diverse ecosystem recovers from perturbation. A depleted one collapses.

Firmicutes-to-Bacteroidetes shift. The two dominant phyla in the human gut shift in ratio. While the exact pattern varies between studies, many aging populations show a relative increase in proteolytic (protein-fermenting) bacteria and a decline in saccharolytic (fiber-fermenting) bacteria. The consequence: less butyrate production, more inflammatory metabolites.

Inflammaging via LPS translocation. As the gut barrier weakens with age — from decreased mucus production, reduced tight junction proteins, and microbiome shifts — bacterial lipopolysaccharide (LPS) leaks into the bloodstream. Even tiny amounts of LPS activate Toll-like receptor 4 on immune cells, driving systemic inflammation. This is “metabolic endotoxemia,” and it’s a major driver of the chronic low-grade inflammation that Claudio Franceschi calls inflammaging.

Bifidobacterium decline. Among the most characteristic changes of the aging gut. Bifidobacterium species — which dominate the infant gut and maintain gut barrier integrity, produce acetate and lactate, and modulate immune function — decline steadily from adolescence onward. By old age, some individuals have virtually undetectable levels.

Reduced short-chain fatty acid (SCFA) production. Butyrate, propionate, and acetate are the metabolic currency of a healthy gut. They fuel colonocytes, maintain gut barrier integrity, regulate immune cell differentiation (particularly T-regulatory cells), modulate brain function via the vagus nerve, and suppress inflammation. As fiber-fermenting bacteria decline, so does this currency.

What Centenarians Teach Us

If the typical aging microbiome deteriorates, what about people who age exceptionally well?

Biagi et al. (2016) studied Italian centenarians and semi-supercentenarians (105+). They found that extreme longevity was associated with a remodeled microbiome — not simply a preserved young one. Centenarians had unique signatures: maintained diversity in some taxa, enrichment of health-associated species, and a surprisingly robust capacity for SCFA production.

Wu et al. (2019) analyzed the gut microbiome of Chinese centenarians and found enrichment in Clostridium cluster XIVa (butyrate producers), Akkermansia, and Christensenellaceae — a bacterial family so consistently associated with leanness and health that it’s been called the most heritable taxon in the human gut (Goodrich 2014).

The centenarian microbiome isn’t young. It’s adapted — maintaining a core of health-associated species while tolerating the inflammatory environment of extreme age. It’s a garden that has learned to grow in difficult conditions.

Key centenarian-associated taxa:

  • Akkermansia muciniphila: Mucin-degrading bacterium that paradoxically strengthens the gut barrier
  • Christensenellaceae: Associated with leanness, metabolic health, and longevity
  • Bifidobacterium (maintained levels): Unlike typical aging decline
  • Butyrate-producing Firmicutes: Maintained SCFA production capacity

Akkermansia muciniphila: The Longevity Bacterium

No single gut species has generated more longevity excitement than Akkermansia muciniphila. It typically comprises 1-4% of the gut microbiome in healthy adults but declines with age, obesity, diabetes, and metabolic syndrome.

Akkermansia feeds on mucin — the glycoprotein layer lining the gut. This seems counterproductive until you realize that mucin degradation stimulates the goblet cells to produce more mucin. It’s like pruning a plant: the cutting promotes growth. The net effect is a thicker, healthier mucus barrier.

Depommier et al. (2019) conducted the landmark randomized, double-blind, placebo-controlled trial in overweight/obese humans. Pasteurized Akkermansia muciniphila supplementation for 3 months:

  • Improved insulin sensitivity
  • Reduced total cholesterol and relevant blood markers
  • Decreased body weight and fat mass
  • Improved gut barrier markers
  • With excellent safety

Notably, the pasteurized (heat-killed) form was more effective than the live form for some metabolic markers — suggesting that a membrane protein (Amuc_1100) mediates many of the effects via Toll-like receptor 2 signaling.

Feeding Akkermansia

You can now buy Akkermansia supplements (Pendulum is the most studied commercial form), but you can also cultivate it through diet:

  • Pomegranate (and pomegranate extract/juice): Ellagitannins are metabolized by gut bacteria into urolithin A, which promotes Akkermansia growth. This is one of the best-studied prebiotic relationships.
  • Cranberry polyphenols: Anhê et al. (2015) showed cranberry extract specifically increased Akkermansia abundance in mice and improved metabolic markers.
  • Concord grape polyphenols
  • Green tea EGCG
  • Caloric restriction and intermittent fasting — both increase Akkermansia abundance
  • Metformin — one of its mechanisms of action is specifically increasing Akkermansia
  • Fiber-rich diets generally support Akkermansia indirectly by maintaining a healthy mucin layer

Butyrate: The Master Metabolite

If there’s one molecule that captures the importance of the gut microbiome in aging, it’s butyrate. This four-carbon short-chain fatty acid is produced by bacterial fermentation of dietary fiber and is arguably the most important metabolite the microbiome produces.

Gut barrier integrity: Butyrate is the primary fuel source for colonocytes. Without it, the gut lining atrophies, tight junctions loosen, and permeability increases. Butyrate literally feeds the wall that separates your blood from the microbial world.

Immune regulation: Butyrate promotes T-regulatory cell differentiation (Arpaia 2013), suppressing inappropriate immune activation. It inhibits NF-kB signaling in immune cells, reducing inflammatory cytokine production. It’s simultaneously anti-inflammatory and immune-enhancing.

Brain function: Butyrate crosses the blood-brain barrier, inhibits histone deacetylases (epigenetic modulation), promotes BDNF expression, and reduces neuroinflammation. It communicates with the brain via the vagus nerve and through direct humoral routes.

Cancer protection: Butyrate induces apoptosis in colorectal cancer cells (the “butyrate paradox” — it feeds normal cells but kills cancerous ones) and maintains DNA repair mechanisms in the colonic epithelium.

The decline with aging — as fiber-fermenting bacteria diminish and dietary fiber intake drops (the average American older adult consumes only 12-15g of fiber daily, far below the 25-35g minimum) — is one of the most consequential microbiome changes in aging.

Restoring Butyrate Production

  1. Dietary fiber diversity: Different fibers feed different bacteria. Variety matters more than total quantity, though both matter. Resistant starch (cooked and cooled potatoes, green bananas, legumes), inulin (garlic, onion, chicory root), pectin (apples, citrus), beta-glucan (oats, mushrooms).

  2. Butyrate-producing probiotics: Clostridium butyricum MIYAIRI 588 (available as a supplement in some markets), Faecalibacterium prausnitzii (not yet available commercially but a key research target).

  3. Tributyrin supplements: A prodrug form of butyrate (three butyrate molecules esterified to glycerol) that survives stomach acid and releases butyrate in the colon. 300-1000mg daily. Better tolerated than sodium butyrate capsules.

  4. Cross-feeding relationships: Bifidobacterium produces acetate and lactate, which are then converted to butyrate by other bacteria (Roseburia, Eubacterium). This is why Bifidobacterium supplementation can increase butyrate production even though Bifidobacterium itself doesn’t make butyrate.

Polyphenols as Microbiome Modulators

Polyphenols — the bioactive compounds in colorful plant foods — are poorly absorbed in the small intestine. Only about 5-10% makes it into the blood. The remaining 90-95% reaches the colon, where it becomes food for the microbiome. This is not a design flaw. It’s the mechanism.

The microbiome metabolizes polyphenols into bioactive compounds (like urolithin A from ellagitannins, equol from soy isoflavones) while the polyphenols simultaneously shape the microbiome — promoting beneficial species and inhibiting pathogens.

Green tea (EGCG): Increases Bifidobacterium and Lactobacillus, reduces Clostridium perfringens. Anti-inflammatory. 3-4 cups daily or 250-500mg EGCG supplement.

Berries (anthocyanins): Blueberries, strawberries, blackberries. The American Gut Project data showed that berry consumption was among the strongest dietary predictors of microbiome diversity. 1-2 cups daily.

Olive oil (hydroxytyrosol, oleuropein): The Mediterranean diet’s gut health benefits are mediated significantly through olive oil polyphenols. 2-4 tbsp extra virgin olive oil daily. The PREDIMED trial showed gut microbiome improvements alongside cardiovascular protection.

Cocoa flavanols: 70%+ dark chocolate or cocoa powder. Tzounis 2011 showed that high-cocoa flavanol intake increased Bifidobacterium and Lactobacillus while reducing Clostridium counts.

Red wine polyphenols (in moderation): Queipo-Ortuno 2012 showed red wine polyphenols increased Bifidobacterium, Enterococcus, and Bacteroides. But alcohol itself damages the gut — the polyphenols may be better obtained from dealcoholized wine or grape juice.

Probiotics for Aging: Strain-Specific Evidence

Not all probiotics are equal. Genus and species tell you the neighborhood; the strain tells you the address. Evidence-based strains for aging:

Lactobacillus rhamnosus GG (LGG): The most studied probiotic strain in history. Strengthens gut barrier, reduces duration of diarrhea and respiratory infections, modulates immune response. Dose: 10-20 billion CFU daily.

Bifidobacterium longum BB536: Specifically studied in elderly populations. Xiao 2003 showed BB536 reduced harmful bacteria, improved bowel function, and enhanced immune response in elderly subjects. Dose: 10-50 billion CFU daily. Directly addresses the age-related Bifidobacterium decline.

Lactobacillus plantarum 299v: Improves iron absorption, reduces IBS symptoms, anti-inflammatory. Particularly relevant for aging adults with marginal iron status. Dose: 10-20 billion CFU daily.

Bifidobacterium animalis ssp. lactis BB-12: Improved immune function in elderly subjects (Arunachalam 2000), increased natural killer cell activity. Dose: 10 billion CFU daily.

Saccharomyces boulardii: Yeast-based probiotic that prevents and treats antibiotic-associated diarrhea (critical in elderly who are frequently prescribed antibiotics) and C. difficile recurrence. Dose: 250-500mg twice daily during and after antibiotic courses.

Fermented Foods vs. Supplements

The Stanford Sonnenburg Lab study (Wastyk 2021, published in Cell) compared high-fermented-food diets versus high-fiber diets over 10 weeks. The fermented food group showed:

  • Increased microbiome diversity
  • Decreased inflammatory markers (IL-6, IL-10, IL-18, CRP)
  • Decreased activation of inflammatory immune pathways

The high-fiber group, surprisingly, did not increase diversity in 10 weeks (though fiber remains essential for feeding existing beneficial bacteria).

The takeaway: fermented foods introduce live microbes and their metabolites in a food matrix that may be more effective than isolated supplement strains.

Practical fermented foods:

  • Yogurt (live cultures, minimal sugar): 1 cup daily
  • Kefir (more diverse strains than yogurt): 1 cup daily
  • Sauerkraut (unpasteurized): 2-4 tbsp daily
  • Kimchi: 2-4 tbsp daily
  • Miso: 1 tbsp in warm (not boiling) water daily
  • Kombucha: 8-12 oz daily (watch sugar content)
  • Natto: Rich source of K2 and Bacillus subtilis

The functional medicine position: fermented foods as the foundation, targeted probiotic supplementation for specific clinical goals, and prebiotic fiber to feed whatever you introduce.

Fiber Diversity: The 30-Plant Rule

The American Gut Project — the largest citizen science microbiome study, analyzing over 10,000 samples — found that the single strongest predictor of a healthy, diverse microbiome was the number of different plant species consumed per week. People eating 30+ different plants weekly had significantly more diverse microbiomes than those eating 10 or fewer, regardless of whether they identified as vegetarian, vegan, or omnivore.

This isn’t about volume. It’s about variety. Thirty different plants sounds daunting until you count herbs, spices, nuts, seeds, grains, legumes, fruits, and vegetables as individual entries. A single mixed salad with five vegetables, two nuts, and an herb dressing covers eight.

Practical strategy for older adults:

  • Keep a weekly plant diversity checklist
  • Add 2-3 new plants each week
  • Herbs and spices count: turmeric, ginger, cinnamon, oregano, rosemary
  • Seeds count: flax, chia, hemp, pumpkin, sesame, sunflower
  • Smoothies are an easy vehicle for 5-8 plants in one sitting
  • Soups and stews accommodate diverse vegetables effortlessly

Fecal Microbiota Transplant: The Frontier

FMT — transferring the stool microbiome from a healthy donor to a recipient — has revolutionized treatment for recurrent Clostridioides difficile infection, with cure rates exceeding 90%. The FDA has approved two FMT-derived products (Rebyota and Vowst) specifically for this indication.

For aging and longevity, the research is earlier stage but provocative:

  • Parabiosis-like effects: FMT from young mice to aged mice reversed hallmarks of aging in the gut, brain, and eyes (Parker 2022, Microbiome). Gut barrier function improved, brain inflammation decreased, and retinal integrity was preserved.
  • Frailty: Preclinical data suggests FMT from healthy donors could reduce frailty markers in aged recipients by restoring SCFA production and reducing inflammaging.
  • Metabolic syndrome: Multiple trials show FMT from lean donors temporarily improves insulin sensitivity in recipients with metabolic syndrome (Vrieze 2012).

The challenges: donor screening is complex, effects are often temporary (the recipient’s diet and environment eventually reshape the transplanted community), and there’s no standardized “longevity donor profile” yet. But the principle — that the microbial ecosystem can be transferred and therapeutically reshaped — is established.

Future directions include defined consortia (specific combinations of characterized strains rather than full stool transplant), phage therapy (using bacteriophages to selectively eliminate pathogenic species), and personalized prebiotics based on individual microbiome sequencing.

A Practical Protocol for the Aging Microbiome

Foundation (daily):

  • 30+ grams of diverse fiber (from 30+ plant sources weekly)
  • 2-3 servings of fermented foods
  • Polyphenol-rich foods: berries, green tea, olive oil, dark chocolate
  • Adequate hydration (dehydration impairs gut motility and mucus production)

Targeted supplementation:

  • Multi-strain probiotic with Bifidobacterium longum, L. rhamnosus GG, L. plantarum (20-50 billion CFU)
  • Akkermansia muciniphila (if available, or feed it with pomegranate and cranberry)
  • Tributyrin 500-1000mg daily (direct butyrate support)
  • Prebiotic fiber: partially hydrolyzed guar gum (Sunfiber) 5g daily or acacia fiber 5-10g daily (well tolerated even in sensitive guts)

Lifestyle:

  • Time-restricted eating (supports microbial circadian rhythms — yes, your bacteria have clocks too, as shown by Thaiss 2014)
  • Exercise (increases microbiome diversity independent of diet — Barton 2018 showed elite rugby players had far greater diversity than sedentary controls)
  • Stress management (chronic stress alters microbiome composition via cortisol and sympathetic nervous system effects on gut motility and secretions)
  • Minimize unnecessary antibiotics, PPIs, and NSAIDs (all disrupt the microbiome)

Testing:

  • Comprehensive stool analysis (GI-MAP, BiomeFx, or similar) for baseline assessment
  • Key markers: diversity indices, Akkermansia levels, butyrate-producing taxa, inflammatory markers (calprotectin, zonulin), pathogenic overgrowth
  • Retest after 3-6 months of intervention

The Soil and the Gardener

Your microbiome at 30 was shaped by decades of diet, environment, medications, stress, and microbial encounters. Your microbiome at 70 will be shaped by what you do from now until then. The garden can be rehabilitated. The soil can be enriched. New species can be introduced and cultivated.

But it requires tending. Not the occasional heroic intervention — the daily, unglamorous practice of feeding the soil. A handful of fermented vegetables. A variety of fiber. A walk after dinner. A night of unbroken sleep.

The centenarians didn’t outsmart their microbiome. They cultivated it — often without knowing they were doing so, simply by living in ways that kept the garden alive.

What are you feeding the 38 trillion organisms that are, at this very moment, deciding how well you age?