Stool From Type 2 Diabetes Patients Disrupts Gut Muscle and Nerves in Mice

Type 2 diabetes does not stay confined to blood sugar. As many as 75 percent of people with the disease report gut symptoms like bloating, constipation, or delayed stomach emptying, and researchers have long struggled to explain why. A new study from the University of Idaho, published in Neurogastroenterology & Motility, points to a surprisingly direct culprit: filtered stool from people with prediabetes and type 2 diabetes contains molecules that can damage gut muscle and nerve activity on contact, at least when transplanted into mice.

Filtered Diabetic Stool Disables Gut Muscle Contractions

The researchers, led by Onesmo Balemba at the University of Idaho, collected stool samples from 49 adults, some healthy, some with prediabetes, and some with confirmed type 2 diabetes, then filter-sterilized them into what the team calls postbiotic stool filtrates, or PSFs. These filtrates were applied directly to lab-cultured segments of healthy mouse intestinal muscle. Filtrates from people with prediabetes or type 2 diabetes sharply reduced how strongly the tissue contracted, while filtrates from healthy donors did not. The prediabetic and diabetic samples also caused visible swelling and sloughing of muscle cells, a sign of direct tissue damage rather than a subtle chemical nudge.

Filtered stool from people with type 2 diabetes cut the contraction strength of healthy gut muscle tissue by nearly half in a lab dish.

Why It Matters for the Majority of Diabetics With Gut Complaints

Gastrointestinal symptoms are one of the most common, and most dismissed, complications of type 2 diabetes. A systematic review and meta-analysis puts gastroparesis, delayed stomach emptying, at close to 10 percent of diabetic patients overall, with broader digestive symptoms affecting a much larger share. With 589 million adults living with diabetes worldwide as of 2024, even a modest slice of that population experiencing microbiome-driven gut damage represents millions of people whose digestive symptoms may have a mechanical, not just metabolic, explanation. Researchers increasingly describe a "microbiota-enteric nervous system axis" in which gut bacteria and their byproducts talk directly to the nerve network that controls digestion, and this study gives that idea a concrete, testable mechanism.

Testing Whether Human Stool Chemistry Translates Into Mice

Beyond the dish experiments, the team gavaged filtrates from type 2 diabetic and healthy human donors directly into the stomachs of healthy mice, three times a week for eight weeks. To track nerve activity in real time, they used genetically engineered mice whose cholinergic gut neurons, the ones that drive peristalsis, glow under a microscope when active. Mice that received diabetic filtrates developed slower gut transit, altered defecation rates, and unusually hyperactive gut neurons compared to mice given healthy filtrates. Pretreating the filtrates with a protease inhibitor or heating them to denature proteins blunted the damage, which points to enzymes and other heat-sensitive molecules in diabetic stool as the likely culprits rather than a single stable toxin.

The Effects Showed Up Almost Entirely in Male Mice

Not every result held up across sexes, and the study is upfront about it. Male mice given diabetic filtrates developed glucose intolerance and the hyperactive nerve signaling described above; female mice largely did not, even though their gut transit slowed similarly. Filtrates from healthy male donors also boosted nerve cell density in the stomach and colon of recipient male mice, an effect diabetic filtrates blocked, but this benefit never appeared in mice that received female donor filtrates, healthy or not. The authors can only speculate why, pointing to estrogen's known anti-inflammatory effects as one candidate explanation. It is also worth being direct about what this study is and is not: it is a mouse experiment using human stool chemistry as an input, not a demonstration that this damage occurs inside a living human gut, and the exact molecules responsible remain unidentified.

What Comes Next: Naming the Molecules

The Idaho team says its next step is identifying the specific proteases and other compounds responsible, since a broad-spectrum protease inhibitor only partially restored gut muscle function, meaning more than one type of molecule is likely involved. They also plan to look at nitrergic neurons, a separate class of gut nerve cells already known to be damaged in diabetes, to see whether the same postbiotic filtrates affect them the way they affect cholinergic neurons here.

References

1. Peter F. Voller, Cameron S. Bowen, Afiya Aunjum, et al. (2026). Postbiotic Stool Filtrates From Patients With Type 2 Diabetes Impair Mouse Intestinal Muscle Contractility Ex Vivo and Alter Enteric Cholinergic Neuronal Activity in Vivo. Neurogastroenterology & Motility. https://doi.org/10.1111/nmo.70401
2. Lianxin Li, Luyao Wang, Ruolan Long, Linrui Song, Rensong Yue (2023). Prevalence of gastroparesis in diabetic patients: a systematic review and meta-analysis. Scientific Reports. https://doi.org/10.1038/s41598-023-41112-6
3. Wang Tao, Yunfeng Yu, Danni Tan, et al. (2025). Microbiota and enteric nervous system crosstalk in diabetic gastroenteropathy: bridging mechanistic insights to microbiome-based therapies. Frontiers in Cellular and Infection Microbiology. https://doi.org/10.3389/fcimb.2025.1603442

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Frequently Asked Questions

Can a person’s gut bacteria really affect someone else’s digestion?

Yes, in a mechanistic sense demonstrated here: stool chemistry alone, without a live microbiome transfer, was enough to alter gut muscle and nerve function in another animal. Related work on [fecal microbiota transplantation in diabetic mice](https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30218-8) has shown gut bacteria composition can shift insulin sensitivity and gut hormone signaling in a recipient, supporting the idea that microbiome byproducts, not just the bacteria themselves, carry biological information across a gut barrier.

Why did the effects only appear in male mice?

The researchers do not fully know. They suspect sex hormones, particularly estrogen’s anti-inflammatory properties, may protect female mice from the same molecules that impair male gut nerves and glucose control. Confirming that will require follow-up studies that manipulate hormone levels directly rather than just comparing sexes.

Could this lead to a new treatment for diabetic digestive problems?

It is an early step, not a treatment. If the responsible molecules are identified and confirmed in people, they could become targets for drugs or dietary interventions aimed at protecting gut nerves in diabetes, or even biomarkers for which patients are at highest risk of digestive complications. That work has not been done yet.