Methanogenic archaea are increasingly being recognized as functional players in the gut’s ecosystem, rather than merely producers of gas. A tightly controlled human feeding study suggests that methanogen levels may even identify patients whose colonic microbiota are particularly efficient at extracting energy from fiber-rich diets.

The findings have implications not only for deeper understanding of the gut microbiome but also for understanding the potential role of methanogens in calorie absorption, and they may help shed light on why high-fiber diets do not always result in weight loss.

During digestion, certain gut microbes ferment fiber into short-chain fatty acids (SCFAs) that the body uses for energy, and in doing so, they produce hydrogen. Too much hydrogen pauses the microbes’ activity, thus interfering with the body’s digestion of fiber, said senior author Rosa Krajmalnik-Brown, PhD, center director and professor, Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, Arizona, told Medscape Medical News.

That’s where methanogens come in. These microbes consume hydrogen and produce methane as a byproduct. Because the body itself can’t produce methane — only the microbes can — methane could serve as a biomarker signaling efficient microbial production of SCFAs and could provide clues to metabolism and energy absorption, Krajmalnik-Brown said.

A Rigorous Approach

The study, published online in The ISME Journal, is a secondary analysis of a 2023 study conducted by the same researchers that aimed to quantify and better understand the contribution of microbes to energy extraction, Krajmalnik-Brown said.

The initial study, conducted at the AdventHealth Translational Research Institute, Orlando, Florida, utilized a crossover diet design consisting of two isocaloric diets: the Western diet (WD) and the microbiome enhancer diet (MBD), which contained more whole foods, fiber, and resistant starch and fewer processed foods than the WD.

The 17 participants (mean age, 30.8 years; 47.1% women) were randomly assigned to consume the WD or MBD for 22 days, 11 as outpatients and 11 as inpatients. They then crossed over to the other diet for an identical 22-day period.

Participants received a low dose of nonabsorbable, nondigestible polyethylene glycol (PEG) with each meal. PEG concentration in fecal samples, together with chemical oxygen demand, were used to calculate mean daily fecal energy losses.

During the inpatient periods, the researchers used whole-room indirect calorimetry — a method in which each participant lived inside a sealed room that measured their body’s metabolism and continuous methane output for a 6-day period.

“The whole-room approach enables the capturing of methane that the body emits as breath and gas over a continuous period,” Krajmalnik-Brown said. “We knew exactly what each participant was eating, and we were able to quantify their energy and energy extraction.”

The study found that consuming the MBD increased the quantity of microbes compared with consuming the WD. Additionally, the MBD provided more energy to the microbes. And the larger quantity of microbes led to greater production of SCFAs, such as butyrate, “which is beneficial for the gut,” she said.

For the current study, the research team focused specifically on methane-producing microbes and investigated their role in hydrogen consumption, SCFA production, and host energy absorption, said first author Blake Dirks, PhD, a graduate research assistant at the Biodesign Center for Health Through Microbiomes.

“There are people who produce a great deal of methane or people who produce very little or no methane at all, without much in-between, which is interesting because that’s not what we usually see with microbes, where we usually see a more even distribution among people,” he said.

Methane Levels Offer Insights

The current analysis found that roughly half of the participants were high methane producers. These patients exhibited increased levels of the SCFA propionate in their blood, but not in their stool, suggesting a faster rate of SCFA uptake than in their counterparts who produced less methane, the authors wrote.

A microbiome network analysis found that the high methane producing participants have a greater abundance of bacteria that break fiber into smaller polysaccharides that other bacteria consume or ferment to produce SCFAs, Dirks said.

“We feel there may be a trophic chain where fiber-degrading bacteria break [fiber] down, and fermentation then produces carbon dioxide and hydrogen, and then the methanogens consume the hydrogen, which in turn encourages more fermentation and fiber degradation,” he said.

Almost all patients absorbed fewer calories on the MBD than they did on the WD, the researchers found. But the high methane producers extracted significantly more metabolizable energy from the MBD food than their counterparts who produced less methane, Dirks said.

This finding indicates that methane levels could shed light on how efficiently people metabolize fiber into energy and help explain why different people get different amounts of calories from the same foods.

Study participants were “relatively healthy,” and it is unknown how the MBD might affect other populations, such as those with obesity, diabetes, or other medical conditions, Dirks said.

Precision Nutrition

High-fiber foods, such as legumes, are generally considered to be components of a healthy diet. For example, the widely recommended Mediterranean Diet features more legumes and other high-fiber foods than the typical WD. However, a common complaint is that foods high in fiber can increase bloating and flatulence.

Methanogenesis may indeed “lead to bloating and it’s not comfortable but — at least based on our data and on information in healthy people — it’s not a process I would recommend trying to avoid,” Krajmalnik-Brown said.

Moreover, people’s concerns about excessive flatulence from consuming beans may be “exaggerated,” according to a study comparing consumption of beans, black-eyed peas, and canned carrots (control).

Dirks said the team’s research needs to be conducted in a larger population. He hopes that doing so will expand the findings and place them into context — particularly the interaction of methanogens with other microorganisms in the human large intestine — and that this understanding will ultimately result in finding interventions to improve people’s gastrointestinal (GI) and metabolic health.

The aim is to figure out how to personalize any intervention that is designed to enhance the composition of the gut microbiome, said Karen Corbin, MD, a spokesperson for the Obesity Society of America, lead author of the 2023 study, and a co-author of the current paper.

In this “precision nutrition” approach, the microbiota could be “remodeled” to optimize human energy balance, which could help to prevent weight gain and even promote weight loss and weight-loss maintenance, Corbin said. “This is a huge open field of possibility to optimize human health,” she added.

The Complexity of Methanogens

Gut microbes “play important roles in harvesting nutrients from the food we eat and making them available to the host,” said Ruchi Mathur, MD, director of the Diabetes Program, Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai, Los Angeles. They can “break down complex starches and fibers that the human host can’t break down, turning them into compounds like SCFAs that can be used as energy sources.”

She said that research she’s involved in shows that microbes in the small bowel, where nutrient harvesting occurs, “appear to play more important roles in weight gain and the development of obesity. We recently showed that the profiles, or patterns, of bacteria present in the small bowel shift progressively in people of normal weight, people who are overweight, and people who have obesity.”

The role of methane is complex, said Mathur, whose research also suggests that higher methane producers may have impaired glucose tolerance when challenged with a high carbohydrate load and may have a higher susceptibility to hyperglycemia.

“Methanogens love fatty foods, and their populations increase dramatically in individuals consuming high-fat diets,” said Mathur, who is also a professor of medicine at UCLA. “This leads to creating further calorie availability and absorption, which can lead to further weight gain, as well as insulin resistance and ultimately diabetes. We have shown that if you reduce methanogen levels in individuals with prediabetes and obesity, you can improve total cholesterol and insulin levels, bringing them closer to normal levels.”

Although Mathur’s research demonstrated that methane is increased in subjects with obesity, “the role of treatment has yet to be defined in these patients,” she said.

Methane plays a role in GI symptomatology, Mathur pointed out. It is a gasotransmitter in the gut and has been associated with a phenotype of constipation — particularly in those with constipation-predominant irritable bowel syndrome. A breath test that uses a substrate of lactulose or glucose can be administered in the patient’s home and mailed in for results, providing a “diagnostic basis for outlining a treatment plan that can include dietary interventions and medications, which may include therapies to address the underlying microbial changes that contribute to the symptoms,” she said.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Krajmalnik-Brown, Dirks, and Corbin reported no relevant financial relationships. Mathur is the founder of the breath testing company Gemelli, which tests for methane, hydrogen, and hydrogen sulfide on the breath.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).