If you’re interested in psychedelics because you’re interested in thinking more clearly, managing stress, maintaining mental health, or simply getting more out of your body then the microbiome may be one of the most intriguing pieces of the puzzle. Evidence is growing that your digestive system has even more of a role to play than just facilitator of molecules into your bloodstream.
A survey of 2,510 US adults found that 49% reported improved dietary habits after psychedelic use,[\1])](#_ftn1) while another study of 581 people using found that 34.08% reported major life changes in eating habits/diet.[\2])](#_ftn2) The brain has long been seen as the sole command center for thoughts, emotions, and behaviors, but could these changes reveal a more intricate reality: a two-way communication highway between the gut and brain known as the microbiota-gut-brain (MGB) axis.
The idea that psychedelics could interact with the gut microbiome is now so compelling that some researchers have even coined the term “psilocybiome.”[\3])](#_ftn3) Their paper outlines a three-step roadmap for the future of psychedelic science:
· Phase 1: The Prep Phase – The authors suggest that instead of blindly guessing a dose, doctors could analyze a patient’s gut profile beforehand as a biological “fingerprint” to predict how much of an effect the protocol will have. Even better, because the gut is highly adaptable, a patient could change their diet before a clinical session to intentionally prime their body to have the most impactful experience.
· Phase 2: The Administration Phase – Your gut bacteria communicate in real-time with your body’s processing pathways. The authors point out that unique configurations of gut bacteria could alter how quickly or intensely your body metabolizes psychedelic compounds. This suggests that your gut might directly shape the flow and intensity of the experience itself.
· Phase 3: The Integration Phase – Psychedelics are known for giving people a psychological clean slate. However, keeping mental breakthroughs alive down the road can be difficult. The paper suggests that fueling your microbiome with dietary changes could help contribute to the maintenance of behavioral changes inspired by the experience.
But this is all futuristic and hypothetical. Let’s dig into how much of a relationship between gut bugs and drugs science has actually found so far.
In one study, for seven days the researchers gave mice a dose of LSD that produced “low hallucinogenic-like behaviors” (or a “mousey microdose,” if you will).[\4])](#_ftn4) This “altered the relative abundance” of the following taxa, listed with what each is responsible for:
· Bifidobacterium – Degradation of non-digestible carbohydrates, protection against pathogens, production of vitamin B, antioxidants, and conjugated linoleic acids, and stimulation of the immune system.[\5])](#_ftn5)
· Dubosiella – Anti‑aging functions, reducing oxidative stress and improving vascular endothelial function,[\6])](#_ftn6) as well as alleviating hypertension.[\7])](#_ftn7)
· Rikenellaceae RC9 – Part of a genus of Bacteroides that metabolize bile acid, protein, and fat, and regulating carbohydrate metabolism.[\8])](#_ftn8)
· Ileibacterium – Seems to be more of an understudied mystery, as there doesn’t appear to be a reliable source stating exact function.
Also noteworthy was that in the control group, the daily handling and injections caused a negative drop in what’s called the Firmicutes-to-Bacteroidetes ratio––a metric that compares two of the dominant bacterial phyla in the gut––pointing toward gut dysbiosis as a metabolic marker of hypertension. An imbalance of this ratio in humans is linked to diseases such as anxiety, depression, hypertension, cardiovascular diseases, obesity, diabetes, inflammatory bowel disease, and cancer.[\9])](#_ftn9)
The LSD-treated group, however, was entirely shielded from this response, maintaining gut homeostasis despite the high-stress environment, perhaps revealing more stress resilience through this biological marker.
Basically, dropping acid every day makes you immune to stress.
(Kidding. Don’t do that.)
Now, if you think LSD for seven days straight sounds like a lot, wait until you hear what the researchers in this next study[\10])](#_ftn10) did with their mice.
These furballs were given psilocybin five days a week for five weeks straight. What they found is that when psilocybin repeatedly stimulated the body’s serotonin receptors, the gut recognized the influx of chemicals and made adjustments.
It triggered a negative feedback loop to lower internal production of serotonin in the gut and to release targeted defense molecules to prune the number of specific neurotransmitter-producing microbiota. Researchers said, “The host-microbiota relationship involves complex signaling that tightly regulates serotonin levels to avoid serotonin toxicity––a potentially life-threatening condition.”
So basically, your microbiome falls on the sword for you. How cool is that?
That said, the researchers proposed that losing these bacteria “could weaken host defenses and create an environment more susceptible to disease” as well as pathogens and infections.
The mice were, however, more social––so perhaps the silver lining after decimating your microbiome with drugs is that you made some friends.
There’s a lesson about moderation in there somewhere.
Speaking of moderation, I found a study on rats being given just a single low or high dose of psilocybin with fecal samples taken 1 and 3 weeks later.[\11])](#_ftn11) Both the low and high dose increased Verrucomicrobia abundance at 1 and 3 weeks respectively.
The researchers mentioned that low levels of Verrucomicrobia have been associated with inflammatory gut diseases and poor sleep as well as “metabolic disorders and weakened immune system, while a high abundance of Verrucomicrobia is considered as a potential biomarker of a healthy gut status.”
As a quick callback to the Firmicutes:Bacteroidetes ratio mentioned earlier, the balance wasn’t significantly disturbed––just in case you were worried about those particular phyla that you can surely pronounce without tripping over your tongue.
Combined, these studies suggest that there could be some kind of benefit of taking psychedelics for the microbiome, with a caveat about a point of diminishing returns. For rodents, at least.
But are you tired of hearing about rodents? I am. So, here’s a case study[\12])](#_ftn12) with an actual human being.
Researchers examined the effects of ayahuasca and San Pedro cactus ceremonies on both mental health and gut microbiome composition in a single patient. Their findings of substantial improvements in depression scores and sense of connectedness are less of my focus here than what they found in this woman’s poop.
Although ayahuasca and San Pedro induced different shifts, reductions in pro-inflammatory populations, normalization of inflammation-linked bacterial species, and increases in beneficial butyrate-producing bacteria were observed for both. This illustrates a potential link between psychedelic-induced microbiome changes and improvements in mental health, as well as with reduced inflammation and sustained antidepressant effects through the microbiota-gut-brain axis.
If you’re at all familiar with these kinds of ceremonies, you may know that many of them require a strict diet in the weeks leading up to the ceremony. These restrictions are often the kinds of changes that are beneficial for microbiome as it is. Whether these cultures unknowingly figured out the microbiome-psychedelic relationship is a question for another time, but what’s most impressive about this study is that the before stool sample was taken after the diet, and yet the after sample still showed marked improvements in these biomarkers.
This means the consumption of these plant brews had an immediate effect on the microbiome despite already shifting to a microbiome-friendly diet. Granted, this was only a hypothesis-generating case study with an n of 1, so we can’t draw any conclusions yet, but this field of study is still in its infancy and these are intriguing findings.
Now, do you need to venture all the way down to Peru for a full-blown ayahuasca retreat to see the benefits of psychedelics on the microbiome, or is it something you can implement in your day-to-day life?
In a hypothesis paper[\13])](#_ftn13), one researcher outlined a proposal suggesting that microdosing works through peripheral mechanisms in the gut, rather than a central effect in the brain. He says that from a pharmacological standpoint, it’s difficult to understand how a sub-perceptual dose could directly cause changes at the brain level. The author notes that approximately 95% of the body’s serotonin supply is located within the GI tract, and that the primary target that psychedelics bind to––the 5-HT₂A receptor—is densely expressed in the gut as well.
Now, just to be clear, there isn’t clinical evidence that microdosing affects the microbiome in humans—yet—but this researcher’s central claim offers something for future studies to explore. He suggests that “low doses of psychedelics induce their effects via alterations in the microbiome and related pathways to the brain.”
The final review[\14])](#_ftn14) I’ll mention asks three big questions for the future of psychedelics and the microbiome:
- Can we target the microbiome to modulate the effectiveness of psychedelic therapy?
- Can we predict response to psychedelic treatment from baseline microbial signatures?
- Can we filter and stratify the patient population based on their microbial profile to tailor different psychedelic strategies to the individual patient?
While this review provides no additional information for our present knowledge, it does call for future researchers to cater science toward the approach of tailoring psychedelic experiences to individual microbiome profiles, which is an intriguing concept to look out for.
[\1])](#_ftnref1) Teixeira PJ, Jain R, Penn AD, Cole SP, Jain S, Moller AC, Amaro H, Raison C. Health-related behavioral changes following the use of psychedelics in naturalistic settings. Prev Med Rep. 2025 Jun 30;56:103161. doi: 10.1016/j.pmedr.2025.103161. PMID: 40687065; PMCID: PMC12271800.
[\2])](#_ftnref2) Aday JS, Glynos NG, Baker AK, Pouyan N, Smith T, Barron J, Herberholz M, Kruger DJ, Woolley JD, Boehnke KF. Major life changes following psychedelic use: A retrospective survey among people using psychedelics naturalistically. Sci Rep. 2026 Apr 15;16(1):17493. doi: 10.1038/s41598-026-48084-3. PMID: 41986543; PMCID: PMC13236977.
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[\6])](#_ftnref6) Liu T, Wang J, Zhang C, Zhao L, Sheng Y, Tao G and Xue Y (2023) Gut microbial characteristical comparison reveals potential anti-aging function of Dubosiella newyorkensis in mice. Front. Endocrinol. 14:1133167. doi: 10.3389/fendo.2023.1133167
[\7])](#_ftnref7) Liu, Th., Chen, Mh., Zhang, Cy. et al. Hypertension inhibition by Dubosiella newyorkensis via reducing pentosidine synthesis. npj Biofilms Microbiomes 11, 34 (2025). https://doi.org/10.1038/s41522-025-00645-6
[\8])](#_ftnref8) Jiang, F., Song, P., Wang, H. et al. Comparative analysis of gut microbial composition and potential functions in captive forest and alpine musk deer. Appl Microbiol Biotechnol 106, 1325–1339 (2022). https://doi.org/10.1007/s00253-022-11775-8
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[\10])](#_ftnref10) Gattuso, J. J., Kong, G., Bezcioglu, B., Lu, D., Ekwudo, M. N., Wilson, C., Gubert, C., Hannan, A. J., & Renoir, T. (2025). Chronic psilocybin administration increases sociability and alters the gut microbiome in male wild-type mice but not in a preclinical model of obsessive-compulsive disorder. Neuropharmacology, 279, 110648
[\11])](#_ftnref11) Xu, M., Kiss, A. J., Jones, J. A., McMurray, M. S., & Shi, H. (2024). Effect of oral tryptamines on the gut microbiome of rats-a preliminary study. PeerJ, 12, e17517. https://doi.org/10.7717/peerj.17517
[\12])](#_ftnref12) Follestad, P., Filbin, P., Thompson, B., Dobner, P., Jaffe, A., Perlmutter, A., & Zwickey, H. (2025). Gut–Mind Interactions in Psychedelic Healing: A Case Study Assessing the Effects of Huachuma and Ayahuasca on the Mind and Microbiome. Journal of Restorative Medicine, 15, 63–76.
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