Hi {{first name | there}},

If you're like me, you may have stopped ordering salads this summer.

Reasonable, considering the news about "explosive diarrhea." The CDC has linked 9,481 illnesses, 398 hospitalizations, and two deaths to the Cyclospora outbreak.

Admittedly though, this reasoning has run its course. The recalled lettuce is already out of stores, and I noticed I am still skipping the salad.

To assuage my own fears and yours, I dug into the facts about what we should be aware of and how to prevent something serious or longer-term (because, as it turns out, food-related GI issues can cause long-term issues).

Longevity medicine is supposed to be about big-picture thinking and precision, so here we go.

TL;DR

In the 1993 study that identified it as a human protozoan pathogen, researchers isolated oocysts from patients and watched them mature. At 25°C or 32°C, they needed 5–13 days to sporulate.

That lag is why the trail goes cold. By the time anyone is sick enough to be counted, the lettuce is weeks gone.

Cyclospora also behaves differently from the bacteria most produce studies research. In a 2008 experiment, researchers inoculated basil and lettuce, then exposed them to gaseous chlorine dioxide for 20 minutes. The treatment cut E. coli by roughly 300 to 9,000 times. It did not affect Cyclospora's ability to sporulate at all.

That is industrial-grade sanitizer, not a salad spinner.

The leaf is working against you too. A 2024 study across five leafy greens found that E. coli attachment tracked with surface roughness, while growth differed with stomatal size and the waxes on the leaf. Lettuce is living tissue with creases, pores, cut edges, and its own chemistry, not a smooth plate that can be wiped sterile.

Heat, on the other hand, works. In another laboratory study, researchers saw no Cyclospora sporulation after exposure at 70°C, or 158°F. (Refrigeration did nothing to stop it over the one week they watched.)

I go into more details here about prevention: Salad Has No Kill Step.

Just in case you were wondering ;)

The vodka idea for killing off food pathogens comes from a single 1996 Salmonella outbreak report, which found that adults who drank alcohol with the meal got sick less often. One observational outbreak, no test of drinking after exposure, and not enough for me to start recommending shots with the salad :D. The CDC has also had to say out loud that the alcohol in a drink does not sterilize contaminated ice.

Probiotics fail for a more interesting reason: they aren't one intervention, and therefore have varied results.

A meta-analysis of 228 randomized trials run between 1970 and 2017 sorted 25 probiotic products across nine types of infections. Effects were specific to the strain and to the disease. L. rhamnosus GG prevents antibiotic-associated diarrhea in children. The same strain didn't work for the other five conditions it was tested against.

The cleanest demonstration is that same strain failing a different job. L. rhamnosus GG is the most-studied probiotic there is. When 971 children with acute gastroenteritis were randomized to it or placebo across ten U.S. pediatric emergency departments, it did nothing: 11.8% had a moderate-to-severe course versus 12.6% on placebo. A Canadian trial of 886 children using a different Lactobacillus combination landed in the same place, 26.1% versus 24.7%.

Same strain, same ages, different problem, opposite answer.

So the genus on the front of the bottle isn't the drug name. "I take Lactobacillus" carries about as much information as "I take an antibiotic." What works is a named strain for a named problem, and so far nobody has tested any strain against Cyclospora.

It feels like outbreaks are increasing. Is that real, or is it coverage?

In the latest comparable FoodNet surveillance, some infection rates stayed near the earlier baseline while others rose. New tests now diagnose far more cases, and sequencing connects infections that once looked unrelated.

We're not clearly getting sicker. We're getting much better at noticing, which I count as a good thing.

Cyclospora is not a toxin that passes through overnight. It is a parasite that completes sexual and asexual stages inside the epithelial cells lining the small intestine.

We know this because researchers actually put cameras to work in the gut. In 17 infected patients who underwent endoscopy, jejunal biopsies showed shortened, widened villi, tissue swelling, dilated capillaries, and a mixed inflammatory infiltrate. The investigators could see multiple stages of the parasite inside the intestinal cells.

This prolonged life cycle happening in your very gut explains why the timing is so confusing. Symptoms usually begin about a week after exposure, sometimes two weeks or more.

If you're wondering whether you had/have a Cyclospora infection, the pattern I'd watch for is watery diarrhea that lasts, improves, then returns.

Why not just test? Routine stool panels don't always include Cyclospora, and the parasite doesn't show up in every sample. Ask explicitly: Did my stool test include Cyclospora, and could I still have it? Ideally, you'd have three separate samples tested (from three different days).

And if it comes back negative while the pattern still fits, that isn't the end of the question. Intermittent shedding is the whole reason one specimen isn't enough. A single negative doesn't rule this out, which is worth saying out loud to the clinician who is about to call it stress.

If you want to learn more, I explain all the details in Cyclospora: The Parasite That Survives the Wash.

“Food poisoning” can describe three phases: a brief illness that will pass, an infection that is still active, or symptoms that remain after the infection clears.

Treating all three the same is where people get into trouble.

Most brief, improving watery diarrhea needs fluids and time, not a blind antibiotic. Cyclospora is different because we have direct evidence that treatment clears the organism and tracks with clinical recovery.

In a 1995 randomized, double-blind trial, 40 symptomatic travelers and foreign residents in Nepal received seven days of TMP-SMX or placebo. Among those who submitted stool at day seven, Cyclospora remained detectable in:

Parasite clearance correlated with feeling better. None of the treated patients relapsed during the additional seven days of follow-up.

So despite the study being quite small, I'd call that enough evidence to convince me to get treatment for Cyclospora.

But since we are in longevity, let's talk about the price. Antibiotics cost you something. In a longitudinal study of healthy adults given four common antibiotic regimens, most microbiomes recovered their pretreatment species richness by two months.

But the mix of species, resistance genes, and metabolic output didn't necessarily come back the same, and a subset of people had a persistent loss of diversity.

Without getting into a whole rabbit hole about the microbiome, which deserves its own newsletter issue, let's just proceed knowing that the microbiome is incredibly important and has broad effects on our health both short- and long-term.

But the choice of whether to take an antibiotic isn't as simple as “parasite or microbiome.” It's balancing the risk vs. the benefits. I wouldn't take an antibiotic for every bad stomach day.

In fact, “just in case” antibiotics have one dangerous potential result. Bloody diarrhea can signal Shiga toxin-producing E. coli. In a meta-analysis of 1,896 patients, the lower-bias studies linked antibiotics with more than twice the odds of hemolytic uremic syndrome. Blood in the stool, high fever, severe pain, dehydration, repeated vomiting, or diarrhea lasting more than three days should lead to evaluation and testing, not a random dose of antibiotics.

That being said, I also wouldn't leave confirmed, symptomatic Cyclospora untreated to protect a theoretical microbiome state or to avoid the above scary outcome.

This is the third phase, and it's the one we don't hear about in the news.

In a 2024 review of 47 studies, 14.5% of people developed post-infectious IBS and 12.7% developed functional dyspepsia. (The risk varied by organism and study, so this isn't specific to Cyclospora.)

A 2026 U.S. medical-record study looked at over 400,000 subjects, half with GI infections and the other half matched controls. After one year, the infection group had 2.35 times the recorded risk of IBS and 2.02 times the risk of functional dyspepsia. The gap was still present at five and ten years.

Then somebody looked at the tissue. In a prospective Campylobacter study, 103 of 747 people developed post-infectious IBS at three months. In the biopsy subset, those with PI-IBS had more serotonin-containing enterochromaffin cells than recovered patients and healthy controls. Both post-infection groups also had more T lymphocytes in the intestinal lining than healthy controls.

Post-infectious IBS is called a disorder of gut-brain interaction because immune signals, serotonin-producing cells, gut movement, sensation, and nervous-system processing can all be involved. It is more than simply psychosomatic, which is unfortunately how these symptoms are often dismissed.

The same study found that depression and enterochromaffin-cell counts independently predicted PI-IBS, suggesting further complex and interesting interactions.

So what do you actually do with that? Not another stool panel, and not another round of antibiotics. Post-infectious IBS and functional dyspepsia get treated as themselves: symptom-directed care, a diet you widen rather than narrow, and a clinician willing to write the diagnosis down. Ask for the name. "Your tests are normal" is not a diagnosis, and it's the most common reason this phase goes unmanaged for years.

None of this is Cyclospora-specific. Nobody has followed a human microbiome before, during, and after this parasite, and nobody has studied what it does to mood, cognition, or immune aging later on. But I mention these studies because chances are, you and your loved ones will experience the wrath of one GI illness or another.

In 60 people with bacterial gut infections, microbiome diversity was lower and antibiotic-resistance genes were more abundant during infection than after recovery.

Meaning the infection is already doing some of what we fear from the treatment. You don't get a pristine gut by declining the antibiotic. You get a longer infection in some cases, plus whatever damage it's doing while you wait.

With Cyclospora, the parasite, intestinal inflammation, repeated diarrhea, a narrower diet, and TMP-SMX all change the gut at once, and we can't separate them with the data we have. This is frustrating, but if you're suffering from symptoms, a commercial stool profile can't tell you whether the problem is persistent infection, temporary lactose intolerance, post-infectious IBS, or something else.

During recovery from a GI illness, I'd start with fluid, salt, and enough food, then widen the diet as appetite returns. Lactose, large amounts of sugar, alcohol, caffeine, and high-fat foods may be harder to tolerate for a while. A temporary intolerance isn't a reason to cut dairy, gluten, legumes, raw produce, and every fermentable carbohydrate for months.

I wouldn't make a generic probiotic a fallback. A review of the better-controlled acute-diarrhea trials found little or no effect on whether diarrhea lasted at least 48 hours. Same problem as before: “probiotic” isn't one intervention.

I know this is where most people reach for a probiotic anyway. The logic is intuitive and I have used it myself: an infection and an antibiotic both disturbed the gut, so put some bacteria back. Just in case.

Somebody actually tested that. In a 2018 study in Cell, healthy volunteers took a course of antibiotics and were then split three ways.

The probiotic group did worst. Their native microbiome came back more slowly and less completely than the group that did nothing at all. The group that got their own bacteria back recovered within days.

The authors open the paper by noting that probiotics are "widely prescribed for prevention of antibiotics-associated dysbiosis." Then they found the prescription working against the thing it was prescribed for.

In the lab, substances secreted by the Lactobacillus appeared to be part of why the native bacteria struggled to re-establish.

So saying "it can't hurt" is cheap and has little evidence to support it, and some evidence showing it can actually do harm.

None of which makes probiotics useless. It makes them a precise intervention just like everything else: a named strain, for a named condition, where somebody ran the trial.

The implicated iceberg is out of stores. I'm ordering salads again.

If you unfortunately fall ill despite all efforts (as I certainly have several times!): wait out the brief illness (unless you are pregnant, immunocompromised, etc. in which case see a healthcare professional), test if symptoms last or return, treat what turns out to be an infection, and stop treating it as an infection once it's gone.

Keep eating plants. Treat according to your individual situation.

Keep learning,

Hillary Lin, MD

P.S. The eating-around-training guide I promised last issue is live: What to Eat Before, During, and After a Workout, organized by session type and length.

A CareCore beta invitation: I'm opening CareCore to a few more beta testers. If you'd like to try an early version and tell me what feels clear or confusing, sign up for beta access. I'm reviewing responses slowly and won't be able to invite everyone at once, but hope to have a more general launch this fall so keep an eye out 👁️

The Biology of Mental Health: Inflammation, Gut Health & Your Brain's Hidden Powers (Part 2)

In this episode, I get into how inflammation and the gut actually reach the brain, and what it changes clinically when you stop treating it as "it's in your head."

Watch on YouTube | Subscribe to The Longevity Show

🩸 Human immune cells enter the brain in middle age. Blood immune cells move in and settle as microglia, a change researchers did not see in mice or monkeys.

🐭 Male mice lived 23% longer with less valine. Cutting the amino acid extended median lifespan, while mTORC1 went up rather than down.

🪜 Six flights of stairs a day stood out. Across 480,000 people, stair climbers were 39% less likely to die of heart disease.

🧠 Estrogen-only HT was linked to 39% lower dementia odds. The study followed 21,462 women and also found less Alzheimer's pathology at autopsy.

🦋 A thymus hormone restored an immunotherapy response. Thymulin made tumors responsive to anti-PD-L1 again by reducing age-related inflammation.

☀️ Belly fat plus low vitamin D was linked to 123% higher mortality. The combined risk was higher than either finding alone.

💉 Retatrutide lowered A1c by 2.0 points. Ninety percent of patients reached the target, compared with a 0.8-point drop on placebo.

⏱️ A clock built to grade drugs, not people. “Pasta” predicts how a compound may shift aging before a human trial.

💊 A gene network flagged old drugs for new aging research. Mapping hallmark genes identified existing drugs that may move aging in either direction.

If someone you love is currently throwing out perfectly safe vegetables, forward them this issue.

Science of Skin Summit, September 17-20, Austin, TX. Speaking on AI in dermatology and skin and hair as windows into biological age.

MVMNT Longevity Summit, September 22-23, Coronado, CA. Leading a session on turning longevity data into clinical action.

Livelong Women's Health Summit, September 25-26, Hilton Midtown, New York City. Joining the expert faculty on AI-driven personalized medicine.

Science of Skin Longevity Summit, February 19-21, 2027, Scottsdale, AZ. Speaking on AI in precision diagnostics and joining the peptides panel.

These partners help support The Longevity Letter:

🐟 Seatopia: sustainable seafood checked for microplastics and mercury. Code HILLARYLINMD for $20 off your first order.

⏱️ Timeline: Urolithin A, studied for mitophagy and muscle mitochondrial biology. The 20% discount applies through the link; there is no code.

🍺 ZBiotics: a probiotic designed to break down acetaldehyde when you drink. Code CARECORE for 10% off.

🧲 CoreViva: whole-body MRI screening for people weighing early-detection tradeoffs. Code CARECORE for $200 off.

🧬 GlycanAge: glycan-based immune age testing with personalized recommendations.

For physician-guided biological age testing, start on the testing page. Options include epigenetic age testing with a consultation, as well as organ-specific proteomic and SystemAge assessments when they fit the question.

Have a question or topic you want covered? Reply to this email.

Was this forwarded to you? Subscribe here to get The Longevity Letter in your inbox.