The Microbiome — What It Is, What Disrupts It, and How to Restore It

YOUR HEALTH — Issue No. 22

You have probably heard that the human body contains more bacteria than human cells. The ratio most commonly cited is ten to one.

That number is wrong.

It was traced back to a rough estimate published in 1972 that was never meant to become a clinical fact — but it spread through the scientific literature and into popular health culture for decades before anyone checked it properly. Researchers at the Weizmann Institute of Science did check it in 2016 — rigorously — and found the actual ratio is approximately 1.3 to one. About 30 trillion human cells and 38 to 39 trillion microbial cells. Close enough that a single bowel movement can temporarily flip the ratio in favor of human cells.

The correction matters not because the exact number is clinically significant — but because it illustrates something important about gut health in general. The field has moved fast. A lot of what circulated as established fact turned out to be a rough estimate nobody had checked. That pattern repeats throughout the microbiome space.

What the microbiome actually is

The microbiome is the collective community of microorganisms living in and on the human body — bacteria, viruses, fungi, and other organisms. Microbes colonize the skin, the nasal passages, the mouth, the lungs, and most significantly, the gastrointestinal tract — with the overwhelming majority concentrated in the colon.

This community is not passive. It digests food that human enzymes cannot break down, produces vitamins including several B vitamins and vitamin K, trains and regulates the immune system, competes against pathogenic organisms, and communicates with the brain through what researchers call the gut-brain axis.

The microbiome is shaped over a lifetime — by birth route, infant feeding, early antibiotic exposure, diet, medications, stress, sleep, and environment. By adulthood it is relatively stable — but not immune to disruption. And the consequences of that disruption are what most people haven't fully heard.

What disrupts the microbiome

Diet is the single most powerful modifiable influence on the gut microbiome. A diet low in plant diversity and fiber — high in ultra-processed foods and refined carbohydrates — consistently produces a less diverse microbiome with fewer beneficial species. The gut environment reflects what you feed it most days.

Medications — and this is where the conversation becomes genuinely important for Plain Medicine's audience.

A landmark study published in mSystems in October 2025 examined electronic health records and stool samples from 2,509 individuals — including medications used years before the stool sample was collected. They found that nearly half of 186 tested drugs had long-term microbiome effects persisting years after the medication was stopped. For some drugs, repeated use produced additive effects — greater disruption with more exposure.

The medications with the most significant microbiome effects:

Antibiotics — among the most powerful disruptors. A single course can significantly reduce microbiome diversity, with recovery taking weeks to months. Repeated antibiotic use compounds the disruption. This does not mean antibiotics should be avoided when clinically necessary — it means they should not be used when they are not. Over prescribing of antibiotics is an issue that every practitioner battles. It is a topic that deserves a dedicated Plain Medicine issue in the near future.

Proton pump inhibitors — PPIs reduce stomach acid, which is one of the gut's primary defenses against bacterial overgrowth. Prolonged PPI use is consistently associated with altered microbiome composition and significantly increased risk of gut infections including C. difficile. PPIs are among the most overprescribed medications in American medicine.

Antidepressants — SSRIs and other antidepressant classes alter gut bacteria composition with effects documented to persist years after stopping. Approximately 90% of the body's serotonin is produced in the gut — the gut-brain relationship is more bidirectional than most people realize.

Other significant disruptors: beta-blockers, benzodiazepines, metformin, NSAIDs, and laxatives all have documented microbiome effects.

Stress — chronic psychological stress alters gut motility, increases intestinal permeability, and changes microbial composition. The gut responds to the nervous system and the nervous system responds to the gut.

Sleep disruption — poor sleep quality reduces microbiome diversity and alters bacterial composition. The gut-sleep connection is well documented.

What happens when it breaks down

Intestinal permeability — what "leaky gut" actually means

The lining of the intestinal tract is a single cell layer thick — one of the thinnest barriers in the human body. It is held together by tight junction proteins that control what passes from the gut into the bloodstream. Nutrients pass through. Bacteria and bacterial products are supposed to stay out.

When the microbiome is significantly disrupted, those tight junctions can loosen. Breakdown products from gut bacteria can cross into the bloodstream in small amounts — things that are supposed to stay contained in the gut. The body's response is chronic low-grade systemic inflammation. That inflammatory state has been linked to metabolic disease, cardiovascular disease, and neurological conditions.

"Leaky gut" as a commercial diagnosis — the version being sold with expensive supplement protocols — is not a recognized clinical entity. Intestinal permeability as a biological phenomenon is real, documented, and clinically relevant. The distinction matters. The biology is worth understanding. The supplement industry's version of it is not.

C. difficile — the clearest example

When antibiotics eliminate the normal microbiome, C. difficile — a pathogenic bacterium that a healthy microbiome normally keeps suppressed — can overgrow, causing severe colitis. This is the most direct evidence that microbiome disruption causes serious disease.

An interesting treatment option: Fecal microbiota transplantation — transferring stool from a healthy donor to restore the disrupted microbiome — is now FDA-approved for recurrent C. difficile. It works because it addresses the root cause directly.

The cardiovascular connection

Certain gut bacteria metabolize compounds found in red meat and other animal products into a molecule called trimethylamine N-oxide — TMAO. Elevated TMAO levels have been associated with increased cardiovascular risk in multiple large studies — promoting atherosclerosis and platelet aggregation.

The honest caveat: this is association, not proven causation. But the association is consistent across multiple studies and the biology is plausible. Worth knowing — and the dietary pattern that reduces TMAO production is the same one that supports a diverse microbiome anyway.

IBD and metabolic disease

Crohn's disease and ulcerative colitis are both associated with a significantly disrupted microbiome — the connection is strong and clinically recognized even if causal direction is not fully established. Microbiome composition also differs consistently between people with metabolic syndrome and type 2 diabetes compared to metabolically healthy individuals — though diet likely explains much of that association.

How to restore it

Diet first — always.

Plant diversity, fiber, and fermented foods are the foundation. These are not exciting answers — they are the correct ones. A 2021 Stanford randomized controlled trial found that high-fermented food diets significantly increased microbiome diversity and reduced inflammatory markers in healthy adults. That is one of the strongest direct human intervention studies in the field.

Thirty different plant foods per week is the target most consistently associated with favorable microbiome outcomes in large population studies. Fiber is the primary fuel source for beneficial gut bacteria. Most adults consume approximately half the recommended daily amount.

Probiotics — the honest picture

Probiotic supplements are a multi-billion dollar industry. The evidence is more specific than the marketing implies — and the strain inside the bottle matters far more than the CFU count on the label.

Specific strains for specific situations have reasonable evidence:

During and after antibiotics — Florastor contains Saccharomyces boulardii, a yeast-based probiotic that survives antibiotic exposure and has strong evidence for reducing antibiotic-associated diarrhea. Culturelle contains Lactobacillus rhamnosus GG — the most clinically studied probiotic strain in the world with over 1,000 published papers — and has good evidence for the same indication. Both are widely available at pharmacies.

For IBS symptoms — Align contains Bifidobacterium 35624, a strain specifically studied for gas, bloating, and abdominal discomfort associated with irritable bowel syndrome.

Generic multi-strain probiotic supplements for general gut health in an otherwise healthy person — the kind with 50 billion CFUs and 30 strains on the label — have much weaker evidence. A 2018 Cell study found that some people's gut microbiomes resisted probiotic colonization entirely — the organisms passed through without establishing.

Plain Medicine translation: if you have a specific clinical indication — antibiotic use, IBS, post-infectious gut disruption — a named strain matched to that indication may help. For general gut health maintenance in a healthy person, fermented foods with live cultures have stronger and more consistent evidence than any supplement capsule.

After antibiotics specifically:

The post-antibiotic gut needs time and fiber more than supplements. Reintroducing plant diversity and fermented foods in the weeks following a course of antibiotics gives the recovering microbiome the fuel and live bacteria it needs to rebuild. The microbiome can recover — but it takes weeks to months, not days.

Sleep:

Protecting sleep quality protects the gut. The relationship is bidirectional — better sleep supports a healthier microbiome, and a healthier microbiome supports better sleep.

Judicious medication use:

Antibiotics only when clinically necessary. Questioning whether long-term PPI use is still needed at every provider visit. Discussing the gut implications of any new long-term medication with your provider. These are not dramatic interventions — they are the kind of clinical conversations the research now clearly supports having.

Plain Gut

Plain Medicine has a free gut health tool at tools.plainmedicine.health/gut — seven questions, a personalized starting point based on your symptoms and habits, and one clear action for the week. No microbiome test required, nothing to buy.

Something worth saying plainly:

The gut microbiome is real, it matters, and the consequences of disrupting it go well beyond digestion. The cardiovascular connection, the metabolic connection, the immune connection — these are not fringe claims. They are the leading edge of mainstream clinical research.

What is also true: the commercial gut health industry has moved faster than the science. Most of what is being sold — cleanses, expensive tests, complex supplement protocols — is not supported by the evidence the underlying biology deserves.

The interventions that actually restore and maintain a healthy gut microbiome are the same ones that have always supported health: eat a wide variety of plants, eat enough fiber, add fermented foods, sleep well, and use medications only when you need them.

That is not a product. That is a practice.

The Member deep-dive this week covers the gut-brain axis in clinical depth — what the bidirectional relationship between gut and brain actually means, the emerging research on microbiome and neurological disease, fecal microbiota transplantation beyond C. difficile, and what the probiotic supplement evidence shows for specific clinical conditions.

Next week: Blood pressure — what your numbers actually mean, when medication is appropriate, and what the evidence shows about lifestyle versus prescription.

Plain Medicine is published for educational purposes only and does not constitute medical advice or establish a patient-provider relationship. Always consult your healthcare provider before making medical decisions.

— Kyle