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Probiotics for pain: eating “good bacteria” to reduce systemic inflammation (Member Post)

 •  • by Paul Ingraham
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Probiotics are pills full of living microorganisms that, in theory, can improve the health of the larger and more diverse community of wee beasties in our bellies, which can in turn help our general health… and maybe, possibly, relieve chronic pain as well? Fingers crossed!

This post explores microbiome science and the implications for pain patients with the sassy skepticism you’ve come to expect from the salamander’s domain.

The conclusion is nuanced. There is no clear 👍🏻 or 👎🏻 for this topic.

As large as our community of bacteria is, by the way, it’s a myth that our bacterial hitchhikers outnumber our own cells ten-to-one — we’re not quite that gross — but they do match us one for one!1) We each have a fully fledged ecosystem in our GI tracts, the gut flora, a dense jungle of diverse micro-critters. “Gut health” refers to the health of that ecosystem of thousands of species.2 Thousands!

The clinical significance of poor gut health (dysbiosis)

If the gut microbiome gets out of whack — if the circle of life down there gets a bit scribbly, formally known as dysbiosis — that seems to have some consequences. Digestive consequences at the least: gas, diarrhea, constipation, pain, and so on.

But grumbly guts might be the least of your worries.

At worst, poor gut health is a driver of disease, even psychological illness (“gut-brain axis”). More literally than “you are what you eat,” you actually are what lives your intestines. It may be impossible to be healthy in general with a muddled gut flora — and that may even be somewhat common, modern diets being a bit of a junk food hellscape.

A scanning electron microscope view of Lactobacillus acidophilus, a common denizen of the gut & a bacterial species with even more of a relationship (a much older one) with Homo sapiens than cows or chickens. Image by Mogana Das Murtey & Patchamuthu Ramasamy, CC BY-SA 3.0, via Wikimedia Commons / colorized, caption removed.

Legitimate science and a bonanza of junk science and snake oil

Junk food is not the only junk we consume regularly: we also live in an era of unprecedented bullshit and hype about every conceivable aspect of health, and the microbiome revolution has been a magnet for cranks and quacks.

It’s been a particular boon for naturopaths, a profession that was thriving on nutrition claims and supplement sales long before there were headlines about gut health. There’s an eyebrow-raising story right here in Vancouver this week about a naturopath who was selling fecal transplants — very closely related to probiotics — basically by harvesting poop from family members.3 To cure autism, no less. 🙄

The legitimate research on this topic so far has mostly been correlative (looking for smoke rather than fire) and preclinical (precious little study of how to actually help people by tinkering with their microbiomes).4 And yet many papers about gut health have already strongly influenced medicine (and quackery).

There does seem to be a robust expert consensus that the microbiome is an important part of our health.5 But can we fix it? Is this stuff ready for the clinic? Let alone self-treatment with supplements?

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“Just add bacteria”: poop bugs in pills to the gut rescue?

Enter probiotics. Let’s be clear here: these are actual intestinal bacteria in a gel-caps. Poop bugs in pills.

They aren’t quite exactly “poop” themselves, but they are a major poop ingredient. The theory is that they are like helpful, hard-working immigrants, new citizens that diversify the intestinal workforce, stabilize its economy. They are often described as “good bacteria,” as though they just cannot help but clean the place up.

See also: pre-biotics — Prebiotics are not bacteria, despite the nearly identical term. They are bacteria food, to encourage the growth of “good bacteria.” It’s like getting a birdfeeder if you want birds in your yard. (And what’s to stop “bad” bacteria from eating the food, like squirrels raiding the birdfeeder? Shhh, don’t ask awkward questions!)

But probiotics are mostly just extra bacteria of the species typically found in large numbers in a healthy gut. The idea is quite simplistic. It’s like trying to improve the health of a jungle by introducing more monkeys… because healthy jungles have lots of monkeys. But is “just add monkeys” actually helpful to a sick jungle? Probably not — ecology is more complicated than that. And, similarly, “just add bacteria” is hardly a guaranteed recipe for gut health salvation either.

Less cynically, the bacteria in probiotics are indeed typical citizens of healthy microbiomes, and it’s definitely not crazy to think that adding more of them might be a normalizing force.

But we have only barely begun to understand how the microbiome even works, let alone how to manipulate it therapeutically. Just flooding your tubes with an assortment of common gut tenants is definitely a wee bit of a hail mary pass. Even if it does work for some people, it is also going to fail for many others, because by nature the composition of the microbiome is highly individual, as unique as a fingerprint — it’s one of the things that makes us who we are, and everyone is different… so “you’re mileage may vary.”

Probiotics science in general

According to the studies, sometimes probiotics do seem to help some health problems. The evidence is generally “promising” — a word that strikes pessimism into heart of any good science junky, because “a promising treatment is the larval stage of a disappointing one.”6 Very few “promising” treatments for anything ever actually get validated.

But there’s less promising and there’s more promising, and the science of probiotics really does seem to be on the happier end of that spectrum, especially for abdominal and digestive distress (like irritable bowel syndrome). So that’s nice.

Not so much for other kinds of pain though — and that’s the focus of this article.

Probiotics for pain: why exactly?

Not so much for other kinds of pain though — and that’s the focus of this article. It’s not entirely if or how gut health affects chronic body pain disorders.7 Many people with chronic pain try probiotics, especially if they have unexplained pain (the worse and weirder your pain, the more open-minded people get). The general idea is that gut stuff seems to drive all sorts of inflammatory stuff (as a well-informed friend of mine put it). So:

poor gut health
⬇️
systemic inflammation?
⬇️
higher vulnerability to many kinds of pain?

“Inflammation” is basically synonymous with “immune system activity,” and poor gut health is analogous to a chronic infection. So a complex immunological reaction is certainly plausible, which is probably how the microbiome affects general health in the first place. And we already know that anything that’s good for gut health is probably good for the rest of our health, and a “rising tide lifts all boats.”

That’s about as specific as the rationale can get, but it’s enough to work with. Using probiotics as a general health tonic is not an unreasonable strategy for desperate patients trying to solve an extremely nasty problem,8 … but it is a crapshoot, make no mistake.

The science of probiotics for pain (is very, very limited)

I won’t be able to cite much evidence on this topic, because very few probiotics trials are relevant to pain.

There is some research on probiotics for treating rheumatoid arthritis, which might be relevant to other common painful problems. If probiotics can calm down the 800-lb gorilla of an inflammatory arthritis, it might also plausibly have an effect on back pain or fibromyalgia. But a 2017 review in Clin Rheumatol was a classic more-study-needed paper: a bit of a signal in the noise (a common inflammatory biomarker was reduced), but clinically? Meh! Probiotics didn’t actually affect the disease.9 In 2022, a review in Nutrients wasn’t even really in the “promising” category:10

Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies' heterogeneity [apples-to-oranges data] do not allow us to propose them to patients with inflammatory arthritis to control their disease.

Meanwhile, a prominent and authoritiative website says, “If you have an inflammatory type of arthritis, probiotics may be especially important”! That “may be” is doing an awful lot of heavy lifting there. 🙄

Probiotics side effects and harms

The probiotics arm of the supplements industry seems as premature as anything I’ve ever seen in this business: a commercial empire rapidly grown from one seed of truth. It’s an obvious “gold rush” to sell probiotics to consumers for every imaginable condition. And we all know that gold rushes can get a bit ruthless and fuel all kinds of shenanigans.

It’s problematic even if we assume that the products all contain what they say they contain, which hardly seems like a safe bet in that barely-regulated industry.11

Remember, these are bacteria, and they can grow out of control and become an infection like any other organism. It’s not likely, but it’s certainly possible.

And bacteria also poop chemicals! Chemicals that may be toxic or just kind of biochemically random. Your microbiome is basically a drug factory. Bacteria produce all kinds of compounds, and that is a major reason why it is relevant to our general health, but that sword has another edge.

Infusions of various common gut bacteria are unlikely to be a serious problem — there’s no known public health disaster unfolding — but on the other hand the supplements industry is also hard at work “innovating” and producing new products with new claims. Quality control could slip.

Reckless overdosing is also a risk. “More is better” thinking is pervasive in healthcare, and plenty of people have made this mistake. I’ve gotten one reader anecdote about excessive probiotics just causing substantial diarrhea, rather than helping IBS.

Probiotics bottom lines

Significant harm from probiotics may be unlikely, but so is significant benefit for most pain patients. I see no specific scientific reason to think that probiotics are going to be useful for patients with any kind of chronic pain (other than irritable bowel syndrome).

Meanwhile, there are clearly safer (and probably cheaper) alternatives, such as live foods (e.g. yogurt, kefir) or even just a substantial diversification of diet.

But I can also see good scientific reasons for some patients to try them — ideally favouring simpler products from well-known brands (which have more to lose from a product disaster). The links between gut health and inflammatory diseases are compelling, and the fairly strong promising-ness of the general research is enough to justify cautious experimentation when the stakes are high.

Notes

  1. Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016 08;14(8):e1002533. PubMed #27541692 ❐ PainSci #52035 ❐

    You may have heard that the human body is infested with ten times as more bacterial hitchhikers than the number of our own cells, and even that they have equal mass. Happily, no, we are not quite that disgusting. There’s “only” about the same number of bacteria as the headcount for our own cells, and — because bacteria are quite a bit smaller than our cells — they weigh just a couple hundred grams on average.

  2. Ruth Ley, commenting on the 10th anniversary of the Human Microbiome Project (HMP, see Human Microbiome Project Consortium), for Nature.com:

    “The result the first comprehensive catalogue of a healthy US human microbiome: a full list of the genes in the microbes in the gut. The HMP showed that the gut’s cellular organisms consist of thousands of species, with a genetic footprint 150 times the size of the human genome. Eventually, this abundance led biologists to view the microbiome as an environmentally acquired ‘second genome’, hidden in the human host.”

  3. Lindsay, Bethany. “Naturopaths ‘not bound by science,’ lawyer argues in B.C. hearing on fecal transplants for autism..” CBC.com. Jun 29, 2022.

    “Klop’s three nephews were the business’s only donors at the time of the complaint and clarified that the lab was in a ground-level unit of the building where the boys lived.”
  4. Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016 Dec;375(24):2369–2379. PubMed #27974040 ❐
  5. Lynch SV, Ng SC, Shanahan F, Tilg H. Translating the gut microbiome: ready for the clinic? Nat Rev Gastroenterol Hepatol. 2019 11;16(11):656–661. PubMed #31562390 ❐
  6. Bastian H. "They would say that, wouldn't they?" A reader's guide to author and sponsor biases in clinical research. J R Soc Med. 2006 Dec;99(12):611–4. PubMed #17139062 ❐ PainSci #51373 ❐

    The full quote:

    “A promising treatment is often in fact merely the larval stage of a disappointing one. At least a third of influential trials suggesting benefit may either ultimately be contradicted or turn out to have exaggerated effectiveness.”

  7. Ma P, Mo R, Liao H, et al. Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice. J Neuroinflammation. 2022 Jun;19(1):169. PubMed #35764988 ❐
  8. Anything good for your general health has the potential to help chronic pain. The specific cause of chronic pain may often be less important than general sensitivity and biological vulnerability to any pain. The biggest risk factors for pain chronicity are things like poor health, fitness, and socioeconomic status, inequality… and they overshadow common scapegoats like poor posture, spinal degeneration, or even repetitive strain injury. How can nothing in particular make us hurt? Because pain is weird, a generally oversensitive alarm system that can produce false alarms even at the best of times, and probably more of them when your system is under strain. See Vulnerability to Chronic Pain: Chronic pain often has more to do with general biological vulnerabilities than specific tissue problems.
  9. Mohammed AT, Khattab M, Ahmed AM, et al. The therapeutic effect of probiotics on rheumatoid arthritis: a systematic review and meta-analysis of randomized control trials. Clin Rheumatol. 2017 Dec;36(12):2697–2707. PubMed #28914373 ❐
  10. Sanchez P, Letarouilly JG, Nguyen Y, et al. Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022 Jan;14(2). PubMed #35057535 ❐ PainSci #52051 ❐
  11. The NIH says that “some probiotic products have been reported to contain microorganisms other than those listed on the label. In some instances, these contaminants may pose serious health risks.”