Gut Microbes Shape How Many Calories We Really Absorb, New Model Suggests
Key Takeaways:
- Researchers at Arizona State University have developed a mathematical model, DAMM, that links human digestion with gut microbial metabolism to estimate how much energy the body actually absorbs from food.
- In a controlled diet study, people following a typical Western diet absorbed approximately 116 more calories per day than those following a high-fibre “microbiome-enhancer” diet, and participants on the higher-fibre plan did not report feeling hungrier.
- Short-chain fatty acids produced by gut bacteria supplied an average of around 140 calories per day, roughly 7.4% of total usable energy, a contribution that conventional food-label calculations do not explicitly measure.
Rethinking the number on the label
The calorie count printed on food packaging might appear to be a simple measure of how much energy a person will gain from eating it. However, that figure does not necessarily reflect the calories the body actually absorbs. One reason for this is that digestion involves far more than the breakdown of food by the body alone – it also relies on the trillions of microorganisms living within the digestive system.
Researchers at Arizona State University (ASU) have developed a mathematical model to explore this often overlooked aspect of digestion. Known as DAMM, short for digestion, absorption and microbial metabolism, the model tracks how food moves through the digestive tract, how much energy the body absorbs directly, and how gut microbes process whatever remains. It also estimates which products of digestion are absorbed and which leave the body as waste.
By accounting for the relationship between diet, human digestion and gut bacteria, the researchers hope to improve understanding of obesity, diabetes and other metabolic disorders. With further development, the approach could eventually help healthcare professionals design diets tailored to individual patients.
“Digestion is not just a human process – it is a collaboration between our bodies and trillions of microbes living in the gut,” said Professor Rosa Krajmalnik-Brown. “DAMM gives us a powerful new way to quantify how those microbial partners contribute to human health and energy balance, and also point at the importance of properly feeding our gut microbes.”
Professor Krajmalnik-Brown is director of ASU’s Biodesign Center for Health Through Microbiomes and a professor in the university’s School of Sustainable Engineering and the Built Environment.
The research team also included ASU Professor Bruce Rittmann, director of the Biodesign Swette Center for Environmental Biotechnology and a Regents Professor of environmental engineering, alongside first author Taylor Davis, an ASU graduate research assistant. Scientists at the AdventHealth Translational Research Institute in Orlando, Florida, also collaborated on the project.
The findings were published in PLOS One.
Why traditional calorie counts miss part of the picture
For more than 100 years, scientists have relied on a system based on Atwater parameters to estimate how much energy people can obtain from food. This method assigns average calorie values to each gram of fat, carbohydrate and protein, and then uses those values to calculate the total energy available.
While this approach is practical and widely used, it cannot fully explain what happens during digestion. In particular, it does not account for how different foods nourish gut bacteria, or how those bacteria transform undigested material into substances the body can use for energy.
Short-chain fatty acids offer an important example. These compounds are produced when microbes in the colon break down fibre and other food components that pass through the upper digestive tract without being absorbed. Some of these fatty acids can then enter the bloodstream and provide additional calories.
To better understand these interactions, the researchers built on an earlier controlled diet study that investigated how the gut microbiome influences human energy balance. The gut microbiome refers to the vast community of bacteria and other microorganisms that inhabit the digestive system.
A high-fibre diet led to 116 fewer calories absorbed per day
In the clinical study, healthy adults followed one of two carefully designed eating plans. The first was a microbiome-enhancer diet containing substantial amounts of fibre and resistant starch, made up of less processed foods and foods with a larger particle size. Resistant starch is a type of carbohydrate that escapes much of the usual digestion in the small intestine, allowing it to reach the colon, where microbes can break it down.
The second eating plan resembled a typical Western diet, with lower amounts of fibre and resistant starch, made up of more processed foods with a smaller particle size.
Although both diets were designed specifically for the study, participants absorbed noticeably different amounts of energy. Those following the Western diet absorbed approximately 116 more calories per day than those following the fibre-rich diet.
Perhaps just as notably, participants following the higher-fibre eating plan did not report feeling hungrier.
The findings suggest that the amount of energy people obtain from food depends partly on its composition and on how it moves through the digestive system. Differences in food processing, fibre content and microbial activity can all influence the final outcome.
For healthcare professionals supporting patients with their diet and weight, findings such as these highlight how food quality and composition – not just calorie totals – may shape energy balance. Understanding the evidence behind nutritional advice is a central theme of The College of Contemporary Health’s Nutrition & Weight Management Essentials CPD course, which supports clinicians in applying nutrition science to everyday practice.
“What is truly unique about the DAMM model is that it quantitatively links human metabolism to the metabolism of the microorganisms in the colon in a way that matches the results from the clinical study and provides fundamental insight into how the microbial community works in partnership with the human host,” Professor Rittmann said.
Gut bacteria can supply about 140 calories a day
The DAMM model offers a more detailed way of following the energy contained in food from the moment it enters the digestive system.
First, it examines the protein, carbohydrate and fat content of a person’s diet and estimates how much usable energy is absorbed in the upper gastrointestinal tract.
It then tracks the remaining material as it moves into the colon. Here, gut microbes break down nutrients that escaped earlier digestion, producing compounds such as short-chain fatty acids. The body can absorb some of these compounds through the colon and use them as an additional source of energy.
The model also accounts for methane production by certain microorganisms known as methanogens, which generate methane as part of their metabolism.
According to the researchers’ calculations, short-chain fatty acids absorbed from the colon supplied an average of approximately 140 calories per day. This represents around 7.4% of the total usable energy obtained from food.
More broadly, the model estimated that roughly 85% of usable energy came from the upper gastrointestinal tract, while approximately 15% came from the lower gastrointestinal tract, where microbes play a particularly important role.
These findings highlight why traditional calorie calculations cannot fully describe human digestion. A meaningful share of the energy available to the body is influenced by microbial processes that conventional food-label calculations do not explicitly measure.
DAMM outperformed the conventional approach
When the team compared DAMM’s predictions with actual measurements from the controlled diet study, the model produced estimates that were closer to the observed calorie absorption than those generated using the conventional Atwater approach.
The older method generally underestimated how many calories participants absorbed. By incorporating microbial metabolism, DAMM provided a more accurate estimate of the energy obtained from the different diets.
How fibre changes the calorie equation
One of the model’s most revealing features is its ability to account for differences between diets.
The microbiome-enhancer diet delivered more fibre and other fermentable material to the colon. This gave gut microbes additional substances to break down, increasing their production of short-chain fatty acids.
DAMM predicted this increase, consistent with the pattern observed in the controlled clinical trial. Participants following the microbiome-enhancer diet had higher levels of short-chain fatty acids in measurements taken from their blood serum and faeces.
These compounds are significant because they illustrate how closely microbial activity and human metabolism are connected. Gut bacteria can transform food components that would otherwise pass straight through the digestive system into molecules the body can absorb and use for energy.
However, producing more of these compounds does not necessarily mean absorbing more calories overall.
In fact, participants following the microbiome-enhancer diet absorbed fewer net calories than those following the Western diet, even though the higher-fibre diet supported greater microbial activity and increased short-chain fatty acid production.
This apparent contradiction becomes easier to understand when the different stages of digestion are examined separately. Although gut microbes can generate additional usable energy, the amount absorbed directly from food in the upper digestive tract also matters.
DAMM helps researchers distinguish between these contributions. It estimates how much energy the body extracts before food reaches the colon, how much energy microbes produce from the remaining material, and how much is ultimately absorbed or eliminated.
Towards more personalised diets and better nutrition
By bringing human digestion and microbial metabolism together within a single mathematical framework, the researchers have created a tool that could help explain why different diets have different effects on the body’s energy balance.
The approach may eventually improve scientific understanding of how diet influences obesity, diabetes and other metabolic conditions. It also raises the possibility of designing nutrition plans that consider not only the nutrients in food, but also how those nutrients interact with the microbes living in each person’s gut.
For now, the model provides a research framework rather than a ready-to-use method for prescribing personalised diets. Further studies will be needed to determine how well it performs across different populations, eating patterns and microbiome compositions.
The researchers also expect the model to become more sophisticated as scientists uncover further detail about how microorganisms and the human body exchange nutrients and energy.
“The DAMM model is more than just a tool for characterizing diet,” Davis said. “It’s a framework designed to evolve. As we discover more on how diet, metabolism and the microbes interact, the new insights can be incorporated into the model, allowing it to grow with us as we learn.”
CCH insight
Research like the DAMM model shows that the conversation around diet and weight is moving beyond simple calorie counting towards a fuller understanding of food composition, fibre and the gut microbiome. If you support patients with nutrition and weight management, our Nutrition & Weight Management Essentials CPD course can help you translate emerging evidence into confident, practical advice.
Explore Nutrition & Weight Management Essentials →
Source: PLOS One
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Gut Microbiome May Shape Responses to GLP-1 Therapies in Obesity and Type 2 Diabetes
Key Takeaways:
- The gut microbiome may contribute to why people respond differently to GLP-1 receptor agonists, although causality remains unproven
- GLP-1 therapies and associated weight loss can alter gut microbial composition, but findings are inconsistent
- Dietary and behavioural changes during treatment are likely key drivers of microbiome shifts rather than direct drug effects
Emerging link between the gut microbiome and GLP-1 treatment response
A recent review published in the Canadian Journal of Physiology and Pharmacology highlights growing interest in the role of the gut microbiota in shaping responses to glucagon-like peptide-1 receptor agonists, commonly referred to as GLP-1 RAs. These medications are widely used in the management of people living with type 2 diabetes and those living with overweight or obesity.
The analysis suggests that gut microbial communities and their metabolites may contribute to the variability observed in treatment responses. At the same time, GLP-1 receptor agonists may themselves influence the composition of the gut microbiota. This bidirectional relationship positions the microbiome as both a potential contributor to treatment variability and a possible future target for more personalised metabolic therapies.
The gut microbiome as a regulator of metabolic health
There is increasing evidence that gut microbes play an active role in metabolic regulation. Preclinical studies using faecal microbiota transplantation have demonstrated that microbial communities can transfer traits such as glucose regulation and body mass. However, findings in human studies have been less consistent.
Despite the widespread use of GLP-1 receptor agonists, research exploring their interaction with the human gut microbiome remains limited. This is particularly notable given the considerable variation in how individuals respond to these treatments. Differences in microbial composition may partly explain this variability, although a definitive causal relationship has not yet been established.
In the review, researchers examined potential interactions between GLP-1 therapies, diet, gastrointestinal symptoms, body weight, and gut microbial composition.
Interactions between GLP-1 signalling and gut microbes
GLP-1 is a naturally occurring hormone that regulates appetite and blood glucose levels by binding to the GLP-1 receptor. It is released by L-cells in the intestine following nutrient intake. Because this release occurs in the lower intestine, GLP-1 operates in close proximity to the gut microbiota, raising the possibility of direct interaction.
Microbial metabolites such as bile acid derivatives and short-chain fatty acids can influence endogenous GLP-1 secretion and activity. These findings suggest that gut microbes may play a role in modulating GLP-1 signalling pathways. However, direct evidence demonstrating that microbial composition determines treatment response to GLP-1 receptor agonists in humans remains limited.
GLP-1 therapies may also indirectly affect the microbiome through changes in appetite, gastrointestinal motility, and dietary intake.
Clinical effectiveness of GLP-1 receptor agonists and variability in response
GLP-1-based therapies including liraglutide, semaglutide, and tirzepatide are now well established in the treatment of type 2 diabetes and obesity. Clinical trials have demonstrated significant weight loss outcomes:
- Tirzepatide – approximately 11.9–17.8% greater weight loss than placebo over 72 weeks
- Semaglutide – approximately 12.4% greater weight loss over 68 weeks
- Liraglutide – approximately 8.0% weight reduction compared with placebo over 56 weeks
Despite these results, individual responses vary widely. Differences in the gut microbiome have been proposed as one potential contributing factor, although this remains an area of ongoing investigation.
Microbiome changes associated with GLP-1 therapies
GLP-1 receptor agonists may influence gut microbial composition in people living with type 2 diabetes and obesity. Historically, obesity has been associated with a higher Firmicutes-to-Bacteroidetes ratio. Some studies suggest that weight loss is linked to increased microbial diversity and a greater abundance of beneficial genera such as Akkermansia.
Clinical observations include:
- Increased Akkermansia levels after six weeks of liraglutide therapy
- Increased levels of Bacteroidota, Actinobacteriota, and Proteobacteria following 12 weeks of semaglutide
- A reduction in Firmicutes in some cohorts
However, these findings are based on a limited number of heterogeneous studies. Many have involved people living with type 2 diabetes who were also taking other medications such as metformin, which is known to independently influence the gut microbiome.
GLP-1 receptor agonists, when combined with lifestyle modification, can lead to approximately 8–20% body weight reduction over several months to one year. Nevertheless, reported microbiome changes remain inconsistent. Some studies show increased diversity, while others report minimal or no significant changes.
Dietary changes during treatment and their microbiome impact
Evidence suggests that observed microbiome shifts may largely reflect downstream effects of weight loss and metabolic improvement rather than direct drug–microbiome interactions.
GLP-1 therapies are associated with changes in eating behaviour, including reduced appetite, increased satiety, and altered taste perception. People using these medications often improve their dietary patterns, with reduced consumption of refined grains, processed foods, beef, and sugar-sweetened beverages. Caloric intake may decrease by approximately 16–39%.
In 2025, organisations including The Obesity Society, American College of Lifestyle Medicine, American Society for Nutrition, and Obesity Medicine Association issued clinical guidance emphasising the importance of nutritional assessment and management of gastrointestinal side effects during GLP-1 therapy.
This guidance recommends prioritising nutrient-dense foods such as vegetables, fruits, whole grains, lean proteins, seeds, and nuts, while limiting refined carbohydrates, sugar-sweetened beverages, red and processed meats, fast foods, and highly processed snacks. Given the strong influence of diet on gut microbial composition, these dietary changes are likely to play a significant role in shaping the microbiome during treatment.
Future directions and research priorities
The review concludes that current evidence points towards behavioural and dietary changes, alongside weight loss, as the primary drivers of microbiome alterations observed during GLP-1 receptor agonist therapy.
However, the gut microbiome remains a promising area for future research. Microbiome profiling could eventually help predict treatment response more accurately in people living with obesity and type 2 diabetes.
Future studies should include:
- Larger and more diverse populations
- Longitudinal monitoring of microbiome changes
- Inclusion of people living with obesity who do not have diabetes
- Detailed tracking of dietary intake, gastrointestinal symptoms, and treatment adherence
Emerging therapies such as oral GLP-1 receptor agonists and new agents like orforglipron may offer further insight into direct interactions between medications and gut microbes, particularly as orally administered drugs come into direct contact with the gastrointestinal tract.
Understanding these relationships may ultimately support more personalised and effective approaches to obesity and diabetes care.
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