Trust Your Gut: The Trillion-Microbe Engine You’re Ignoring
My wife is pointing at a pot.
We’re somewhere outside Rangoon. Early 2010s. Myanmar has barely opened to tourists. We’d flown into Thailand for a few days, then crossed straight into a country that didn’t appear in any guidebook we owned. The “restaurant” is a woman with a gas burner and some plastic stools under a tarp. There’s no menu. There’s no fridge. There are flies, and they seem confident about their dining choices.
She points. I point. Same pot. Same spoons. Same cheerful disregard for anything a food safety inspector would recognize.
We walk back to the guesthouse happy and full, feeling like the kind of travelers who say yes to everything.
The next morning, she can’t move. Not “I feel a bit off” can’t move. The bathroom-floor, bargaining-with-the-universe, reconsidering-every-life-choice kind of sick. It lasted days. I brought her water and crackers and tried to look sympathetic, while honestly feeling completely fine. Not a cramp. Not a rumble. Nothing.
I spent two days exploring Rangoon alone. Shwedagon Pagoda at sunrise. Tea shops in back alleys. More street food from vendors I couldn’t vet. Zero consequences.
This wasn’t the first time. It had happened in Nepal. It had happened in half a dozen countries before that. Same plate, opposite outcomes. She called my digestive system “stupid and incapable of detecting the most obvious of germs.” I called it supernatural.
We never settled the argument. We probably never will.
But something else about the gut has followed me even longer.
I spent years at McKinsey and BCG. I’m trained to build fact bases, structure problems, and propose decisions that look rational on paper. I can make a case for almost anything if you give me enough data. But every major private decision I’ve made in life, the ones that actually mattered, I made on feel.
When I quit consulting to join a startup in New York, I didn’t have a model that justified it. I had a feeling. Deep, steady, and completely immune to counterarguments. That single decision gave us a decade in a city that changed who we are. Two of our three kids were born there. Friendships that still hold after all these years. Experiences we couldn’t have planned, no matter how much analysis we did.
Gut feel. Every time I followed it, something good came out the other side. Every time I overrode it with logic, I regretted it.
I never really questioned why that worked. I just trusted it. Turns out, the biology behind it is stranger and more interesting than I expected.
The Chemical Plant Between Your Ribs
Your gut isn’t a tube that processes lunch. That’s the version you learned in school, and it’s wrong.
It’s a chemical factory staffed by roughly 100 trillion microorganisms, functioning more like an endocrine organ [1]. It produces bioactive compounds that regulate your metabolism, train your immune system, and directly influence your brain chemistry [2]. You have more bacterial cells in your gut than human cells in your entire body. Let that sit for a moment.
The core mechanism is simple enough to explain over dinner. When you eat fiber, you can’t fully digest it. Your gut bacteria can. They ferment it, releasing short-chain fatty acids, the most important of which is butyrate. Butyrate provides up to 70% of the energy your colon cells need to function [3]. It suppresses the expression of inflammatory genes [4]. In plain language, it keeps the gut wall sealed tight and your immune system from overreacting to things that aren’t threats.
When the wall weakens (and it will, if you stop feeding the bacteria that maintain it), fragments of bacterial cell walls called lipopolysaccharides leak into your bloodstream. Your immune system treats this as an invasion. The result is a state researchers call “metabolic endotoxemia” [5]: chronic, low-grade inflammation that hums in the background of your biology. That’s the afternoon brain fog that sleep doesn’t fix. The immune system is running hot with no clear infection. The slow metabolic erosion that shows up in bloodwork years before anyone calls it a diagnosis.
About 70% of your immune cells live in your gut [6]. The microbiome trains them. Diverse ecosystem, calibrated immune response. Depleted ecosystem, overreaction, and vulnerability. This isn’t a wellness talking point. It’s immunology.
I didn’t have any of this vocabulary in Myanmar. I just knew my wife got destroyed by the same food that didn’t even register in my body. What I didn’t know was that something I’d never deliberately fed, supplemented, or thought about once was running a defense operation sophisticated enough to make my consulting frameworks look like finger paintings.
When Your Calendar Becomes the Enemy
I need to be honest about something. For all the years I’ve studied health, tracked biomarkers, and written about longevity, I’ve also been the guy eating room service at midnight after three flights in a week. Popping ibuprofen for travel headaches without a second thought. Running on espressos through back-to-back meetings and calling it a strategy.
If you’re an ambitious professional, you’ve done some version of this. Probably this week.
Turns out that lifestyle is exceptionally good at destroying the exact system I just described.
Chronic stress raises cortisol. Cortisol increases intestinal permeability. But here’s what surprised me: it also activates virulence genes in certain gut bacteria, literally making them more aggressive under your own hormones [7]. Your bacteria don’t just sit there while you white-knuckle through a quarter. They respond. Not helpfully. People under high perceived stress consistently show lower microbial diversity [8]. Fewer species. Fewer defenses. Less resilience.
Then there’s timing. Your microbiome runs on a 24-hour clock, synchronized to when you eat, not what you eat [9]. Disrupt that rhythm with late-night meals, timezone hopping, or even weekend sleep-ins (researchers call this “social jetlag”), and you promote metabolic dysfunction that has nothing to do with food quality. Eran Elinav’s lab at the Weizmann Institute showed that jet-lagged mice developed obesity-prone microbiome profiles. Transfer those microbes to germ-free mice? Weight gain. Impaired glucose control. From the microbes alone [10].
And medications. Those PPIs you take for reflux during stressful quarters? They significantly alter the gut microbiome by raising gastric pH, allowing oral bacteria to colonize the lower intestine [11]. NSAIDs damage the lining directly [12].
Picture the scene. Three time zones this week. Ibuprofen for the headache. A PPI for the reflux that’s been flaring since the board dinner. Midnight burger from room service because you missed a real meal. Every single lever is pulling in the wrong direction at once. My wife would get wrecked by one pot in Myanmar. Many of us are doing this to ourselves five days a week and calling it professional life.
Your $300 Gut Test Is Telling You Nothing Your Groceries Can’t Fix
The microbiome testing industry wants your credit card. Direct-to-consumer stool tests promise personalized insight into your gut. The problem: they can’t deliver.
There’s no agreed-upon definition of a “healthy” microbiome. Two perfectly healthy people can share less than 10% of their microbial species and still have identical metabolic function, because different bacteria can do the same jobs [13]. Your stool sample captures what’s passing through (the luminal population), not what’s attached to the intestinal wall, actually talking to your immune system (the mucosal population) [14]. You’re analyzing the ecosystem’s trash, not its residents. Results shift with what you ate this week, how you slept, what medications you took.
The real problem is actionability. “You have low Akkermansia” leads to the same advice as every other result: eat more fiber, eat more polyphenols, sleep better. The test converges on recommendations you could have gotten for free.
Skip it. Track functional biomarkers instead: hs-CRP for inflammation, HbA1c for metabolic health, ApoB for cardiovascular risk. Those measure what the microbiome is actually doing downstream. Spend the $300 on groceries.
The Highway Between Your Gut and Your Brain
Remember when I said I’ve made every important decision on gut feel? There’s a physical highway that explains why that’s not as irrational as it sounds.
About 90% of your body’s serotonin is produced in the gut [15]. Under normal conditions, microbes support the conversion of tryptophan into serotonin. Under chronic stress, a competing pathway hijacks that tryptophan and diverts it toward neurotoxic metabolites [16]. Less serotonin precursor. More neuroinflammation. A depletion loop that connects gut health directly to mood, sleep quality, and how clearly you think under pressure.
The vagus nerve carries signals between the brainstem and gut in both directions. In animal studies, the probiotic Lactobacillus rhamnosus altered GABA receptor expression in the brain through vagal signaling. Sever the nerve, and the effect vanishes [17]. In humans, the specific strain Bifidobacterium longum 1714 modulated neural oscillations associated with coping and blunted cortisol response to social stress in healthy volunteers [18]. Not a vague “gut-brain connection.” A measurable biological buffer for people in high-pressure environments.
The board meeting where you can’t think straight. The negotiation you almost walked away from because something felt off. The career move that made no sense on paper but turned out to be the best decision of your life. That signal had to travel somewhere. It traveled through here.
Your Post-Flight Probiotic Ritual Is Probably Backfiring
The supplement industry sells gut health the way it sells everything: more is better, broad spectrum, high dose. Pick up any airport probiotic, and you’ll find “50 billion CFU” across 15 strains backed by zero clinical evidence for healthy adults.
It gets worse. A landmark 2018 study in Cell found that generic multi-strain probiotics taken after antibiotics delayed and impaired native microbiome recovery compared to doing nothing [19]. The probiotic slowed things down, not sped them up.
Precision matters. Only a handful of strains have real human data. Saccharomyces boulardii CNCM I-745 (a yeast) shows significant efficacy for traveler’s diarrhea prevention across multiple meta-analyses (RR = 0.79, p < 0.001) [20] and antibiotic-associated diarrhea (RR = 0.47, 95% CI 0.35-0.63) [21]. As a yeast, it survives antibiotics. Lactobacillus rhamnosus GG has solid evidence for antibiotic-associated diarrhea taken during the course, separated 2-3 hours from the dose [22]. And B. longum 1714 for stress modulation, as above [18].
Three strains. With receipts. Everything else on that shelf is marketing.
Try This Today
The Kitchen Close. Stop eating 3 hours before bed. Maintain a 12-hour fasting window. This lets the Migrating Motor Complex, your gut’s self-cleaning wave, complete its cycle and keeps your circadian-microbiome coupling intact [9][23]. During travel weeks, this is the single most important thing you control. The minibar is right there. Close the kitchen anyway.
The Fiber Floor. 30 grams of mixed fiber daily. Fastest backup: 1 tablespoon of psyllium husk plus 1 teaspoon of inulin in water, takes 30 seconds. But real food first. Lentils (15.6g per cup cooked), chickpeas (12.5g), avocados, berries, oats. Aim for 30 different plant species a week; herbs and spices count [24]. The 2019 Lancet meta-analysis across 185 studies and over 3.5 million participants found that 25-29 grams of daily fiber was associated with 15-30% lower all-cause mortality [25]. That’s one of the strongest dose-response relationships in nutrition science.
The Fermented Ramp. One serving of fermented food daily. Kefir, Kimchi, Sauerkraut, yogurt. Built to 3 over 4 weeks. A Stanford trial found that 6 servings per day decreased inflammatory markers and increased microbial diversity more effectively than a high-fiber diet alone over 10 weeks [26]. You don’t need 6. Start with 1.
The Investment, Not the Hack
This sits in the Activate pillar of my Upward ARC framework. Not Recover. Not Capacity. Activate. Because the microbiome is the biological substrate on which everything else runs. Sleep quality, training adaptation, stress resilience, and immune defense. Degrade this system, and every other investment underperforms.
It’s not a weekend project. It’s a compounding investment. Fiber, fermented foods, consistent meal timing, and targeted supplementation when warranted. Small inputs, accumulated over weeks and months, build a different biological baseline. Consistency beats perfection. Every single time.
I’ve trusted my gut my whole life. The iron stomach that carried me through Myanmar while my wife spent two days on a bathroom floor. The instinct that told me to leave a prestigious consulting career for an uncertain startup in New York was a move that gave us everything we didn’t know we needed. She still thinks my digestive system is “stupid.” Maybe it’s time I started feeding the thing that’s been carrying me all along.
Stay healthy.
Andre
References
[1] Sender, R., Fuchs, S., & Milo, R. (2016). Revised estimates for the number of human and bacteria cells in the body. Cell, 164(3), 337-340.
[2] Badal, V. D., et al. (2020). The gut microbiome, aging, and longevity: A systematic review. Nutrients, 12(12), 3759.
[3] Donohoe, D. R., et al. (2011). The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metabolism, 13(5), 517-526.
[4] Davie, J. R. (2003). Inhibition of histone deacetylase activity by butyrate. Journal of Nutrition, 133(7), 2485S-2493S.
[5] Cani, P. D., et al. (2007). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 56(7), 1761-1772.
[6] Vighi, G., et al. (2008). Allergy and the gastrointestinal system. Clinical & Experimental Immunology, 153(Suppl 1), 3-6.
[7] Lyte, M. (2014). Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes, 5(3), 381-389.
[8] Madison, A., & Kiecolt-Glaser, J. K. (2019). Stress, depression, diet, and the gut microbiota: Human-bacteria interactions at the core of psychoneuroimmunology and nutrition. Current Opinion in Behavioral Sciences, 28, 105-110.
[9] Thaiss, C. A., et al. (2014). Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell, 159(3), 514-529.
[10] Thaiss, C. A., et al. (2016). Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell, 167(6), 1495-1510.
[11] Imhann, F., et al. (2016). Proton pump inhibitors affect the gut microbiome. Gut, 65(5), 740-748.
[12] Bjarnason, I., et al. (2018). Mechanisms of damage to the gastrointestinal tract from nonsteroidal anti-inflammatory drugs. Gastroenterology, 154(3), 500-514.
[13] Human Microbiome Project Consortium. (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486(7402), 207-214.
[14] Zmora, N., et al. (2018). Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell, 174(6), 1388-1405.
[15] Yano, J. M., et al. (2015). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161(2), 264-276.
[16] Agus, A., Planchais, J., & Socaci, S. (2018). Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host & Microbe, 23(6), 716-724.
[17] Bravo, J. A., et al. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050-16055.
[18] Wang, H., et al. (2019). Bifidobacterium longum 1714 strain modulates brain activity of healthy volunteers during social stress. American Journal of Gastroenterology, 114(7), 1152-1162.
[19] Suez, J., et al. (2018). Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell, 174(6), 1406-1423.
[20] McFarland, L. V. (2018). Meta-analysis of probiotics for the prevention of traveler’s diarrhea. Travel Medicine and Infectious Disease, 27, 33-37.
[21] McFarland, L. V. (2010). Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World Journal of Gastroenterology, 16(18), 2202-2222.
[22] Szajewska, H., & Kołodziej, M. (2015). Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Alimentary Pharmacology & Therapeutics, 42(7), 793-801.
[23] Deloose, E., et al. (2012). The migrating motor complex: Control mechanisms and its role in health and disease. Nature Reviews Gastroenterology & Hepatology, 9(5), 271-285.
[24] McDonald, D., et al. (2018). American Gut: An open platform for citizen science microbiome research. mSystems, 3(3), e00031-18.
[25] Reynolds, A., et al. (2019). Carbohydrate quality and human health: A series of systematic reviews and meta-analyses. The Lancet, 393(10170), 434-445.
[26] Wastyk, H. C., et al. (2021). Gut-microbiota-targeted diets modulate human immune status. Cell, 184(16), 4137-4153.
A note for new readers:
I’m a trained reconstructive facial surgeon, medical doctor, and dentist. Before launching this newsletter, I had a varied career: competitive freestyle wrestler, management consultant (McKinsey), entrepreneur (Zocdoc, Thermondo, and docdre ventures), and corporate executive (Sandoz). Today, I’m a Managing Director and Partner at BCG.
Husband of one. Father of three. Split between Berlin’s urban pulse and our Baltic Sea retreat. I’d rather be moving than sitting. Not just hobbies. Research. My body is my primary laboratory; I’ve been conducting experiments for decades.
If this is your first time here, welcome. I’m excited to share what I’ve learned and will continue to learn with you.
DISCLAIMER:
Let’s get one thing straight: None of this, whether text, graphics, images, or anything else, is medical or health advice. This newsletter is here to inform, educate, and (hopefully) entertain you, not to diagnose or treat you.
Yes, I’m a trained medical doctor and dentist. No, I’m not your doctor. The content here isn’t a replacement for professional medical advice, diagnosis, or treatment.
If you have questions about your health, talk to your physician or a qualified health professional. Don’t ignore their advice or delay getting care because of something you read in The Upward ARC. Be smart. Do your research. And, as always, take care of yourself.