A soil bacterium may help protect the gut during chemotherapy and antibiotics

A soil bacterium could help protect the gut in some of its most vulnerable moments – from chemotherapy to chronic disease – by triggering the intestine’s own repair mechanisms, according to new findings from researchers at the University of Copenhagen.

Benjamin Jensen, now Associate Professor at the Department of Biomedical Sciences, University of Copenhagen, first came across Methylococcus capsulatus more than a decade ago during his PhD, when he was discussing whether climate-friendly foods might also influence the immune system with colleagues in Norway.

“There was an old gas station company that used it to get rid of the methane while they were extracting the oil,” Jensen recalls.

Its ability to turn methane from natural gas into digestible protein led to the development of M. capsulatus as animal feed – a solution with both climate-related benefits and unexpected effects on animal health.

To test this idea, Jensen and his team turned to a set of complementary mouse models designed to mimic people whose gut lining is under attack – during chemotherapy, after antibiotics or in chronic inflammatory bowel disease.

Across these models, in experiments presented in Nature Communications, the team found that M. capsulatus helps to rebuild the intestinal lining and dampen inflammation in mice by shifting immune activity – two processes that often break down among people undergoing treatment or living with chronic disease.

“What we think this can do is repair the gut when it is failing – closing ulcers and restoring the lining,” Jensen says – something current treatments often struggle to achieve.

Umami bacteria that soothe the gut

Jensen and his team used a commercially available animal feed made from a microbial lysate of M. capsulatus – essentially broken bacterial cells, dried into a powder. The result is nutrient-dense with a “very strong umami flavour” but contains no live bacteria. “It is just like other protein supplements – you could imagine sprinkling it on your cereal for breakfast,” Jensen explains.

The researchers fed the microbial lysate, dubbed M. capsulatus Bath (McB), to these mouse models.

In one line of evidence, using a model of colitis, “we basically disrupted the large intestine of mice” using chemical irritants to mimic the breakdown of the intestinal lining affecting people with the disease. While mice fed a normal diet eventually “succumbed” to the disease, Jensen said those receiving McB were “largely protected – they showed a much healthier gut and were more resistant to the disease.”

In a second, very different model, in mice receiving chemotherapy, McB relieved mucositis, a punishing side-effect in which the protective lining of the gut becomes inflamed and damaged.

“Often, it leads to dose reductions of the chemotherapy, which can make treatment less effective and prolong the course in patients.”

“We think this could be a form of supportive care – not treating the cancer per se but mitigating side-effects so that patients may be able to stay on treatment and potentially receive more effective doses.”

And in a third model, mice taking antibiotics were spared the diarrhoea that often follows treatment when given McB.

Work locally – in the gut

But how does this soil bacterium actually soothe the gut in all these different situations? Across the models, they found that the microbial lysate activates a hormonal pathway called GLP-2, which plays a key role in how the gut repairs itself.

GLP-2 is a sister hormone to the better-known GLP-1 but serves a different purpose, Jensen explains. In addition to its diabetes-related effects through increased insulin secretion, GLP-1 affects how quickly food moves through the digestive tract, Jensen says. “When you do not have as many bowel movements, you feel full for longer, so you eat less.”

Instead, GLP-2 appears to trigger the birth of new intestinal cells – a process that is often suppressed during treatment, when therapies targeting rapidly dividing tumour cells also slow renewal in the gut, where cells divide rapidly.

GLP-2 also seems to stimulate the production of mucus. “It is very important as a protective lubricant in the gut, so that stool moving through the intestine does not get stuck. At the same time, it helps protect against the millions of bacteria naturally living in our intestines – bacteria we very much want to keep there, but not crossing the epithelial barrier.”

There are several GLP-2 drugs on the market, but these are typically only prescribed to people with short-bowel syndrome, Jensen says. That is because these drugs are delivered via injection, leading to effects around the body, and there is concern that the boost to cell proliferation that is so helpful in the lining of the gut could potentially increase the risk of cancer in the intestine or other tissues.

But eating McB may help place these GLP-2 initiators exactly where we want them – on the intestinal lining rather than out in the bloodstream. “We do not want this to go into circulation. We want to work on the gut barrier, to work locally in the gut,” he says.

Calming the immune response without shutting it down

The team also uncovered a second, parallel mechanism across the models, likely involving the immune system. T cells act as the enforcers of the immune system, identifying and attacking invading pathogens – part of a normal inflammatory response. But sometimes the mechanism that turns off this response goes haywire, meaning that inflammation persists and T cells begin attacking the body’s own tissues.

Even in chronic inflammatory conditions such as inflammatory bowel disease, avoiding treatments that would tamp down the inflammatory system across the body is important.

“If you get an infection in the liver, you would like those cells to be able to fight off that pathogen,” Jensen explains. “If you do not have inflammation at all, you die within three to four days, because it is impossible to live without having an effective immune response.”

Consistently across the models, mice fed McB had higher levels of regulatory T cells, which help to switch off inflammation once a threat has passed in both the small and large intestine.

“We call it a tolerogenic immune profile, and that is very important,” Jensen says. Without a hyperactive immune response, the mice consistently recovered faster, alongside signs that the tissue could repair itself more effectively, they found.

From mice to potential treatments

Jensen says he does not envision sprinkling the savoury McB powder on dinner plates in cancer wards. “The doses we used are not directly translatable,” he says. “You would have to change at least 20% of your diet to this bacterial lysate, which is really difficult to convince people to do.”

Instead, the researchers hope to isolate the specific molecules in the lysate responsible for these effects and produce a pill with the same therapeutic effects.

“Two or three years from now, we should have a very strong candidate that has been validated in animal models,” he says. “Within four or five years, there could be a candidate ready for human testing.”

If the findings translate to humans, such treatments could become a lifeline for people with debilitating conditions such as inflammatory bowel disease. “Even the best treatments we have for irritable bowel disease only help approximately 50% of patients,” Jensen explains.