Real time measurements of intestinal gases: a novel method to study how food is being digested

Researchers in Wageningen (The Netherlands), have been able to identify for the first time, how gut microorganisms process different types of carbohydrates by measuring in real time the intestinal gases of mice. This is not only a novel method to understand how food is digested but could also tell us more about the role of gut microorganisms in gut health.

Intestinal gases

The intestinal microbiota is a diverse and dynamic community of microorganisms which regulate our health status. The advancement of biomolecular techniques and bioinformatics nowadays allows researchers to explore the residents of our intestines, revealing what type of microorganisms are there. However, studying only the microbial composition of an individual provides limited insights on the mechanisms by which microorganisms can interact with the rest of our body. For example, far less is understood about the contribution of the gut microorganisms in the production of intestinal gases such as hydrogen, methane and carbon dioxide through the breakdown of food and how these gases affect the biochemical pathways of our bodies.

Intestinal gases consist mostly of nitrogen, and carbon dioxide, which originate primarily from inhaled air. Hydrogen and methane though, are produced as by-products of carbohydrate fermentation (break down), by intestinal microorganisms. However, not all carbohydrates are digested in the same way. For instance, food with simple sugars can be rapidly absorbed in the small intestine unlike complex carbohydrates such as fibers, which reach the colon where they are digested by the colonic microbiota.

Lower_digestive_system

Measuring hydrogen in mouse intestines

To study these interactions and gain knowledge on how microorganisms process carbohydrates, the research team led by Evert van Schothorst from the Human and Animal Physiology Group of Wageningen University (WU) in collaboration with the WU-Laboratory of Microbiology fed mice two different diets with the same nutritional values but with different types of carbohydrates (1). The first diet contained amylopectin, a carbohydrate which can be digested readily in the small intestine while the second diet contained amylose, a slowly digestible carbohydrate that is digested by intestinal microorganisms in the colon.

Animals fed the easily digestible carbohydrates showed minimal production of hydrogen whereas the group fed with the complex carbohydrates presented high levels of hydrogen. Moreover, the two groups were characterized not only by distinct microbial composition (different types of bacteria present) but also distinct metabolic profiles (short chain fatty acids), suggesting that the type of carbohydrate strongly affects microbial composition and function.

The importance of hydrogen

Hydrogen consumption is essential in any anoxic (without oxygen) microbial environment to maintain fermentative processes. In the intestine it can be utilised through three major pathways for the production of acetate, methane and hydrogen sulphide. These molecules are critical mediators of gut homeostasis, as acetate is the most predominant short chain fatty acid produced in mammals with evidence suggesting a role in inflammation and obesity (2). Methane, which is produced by a specific type of microorganisms, called archaea, has been associated with constipation related diseases, such as irritable bowel syndrome(3) and also recently with athletes’ performance (4)! Finally hydrogen sulphide is considered to be a toxic gas, although recent findings support the notion that it also has neuroprotective effects in neurodegenerative disorders such as Parkinson and Alzheimer diseases (5).

To the best of our knowledge, this is the first time that food-microbiota interactions have been studied continuously, non-invasively and in real time in a mouse model. Hydrogen is a critical molecule for intestinal health and understanding its dynamics can provide valuable information about intestinal function, and deviations in conditions such as Crohn’s disease or irritable bowel syndrome (IBS).

Further reading

1. Fernández-Calleja, J.M., et al., Non-invasive continuous real-time in vivo analysis of microbial hydrogen production shows adaptation to fermentable carbohydrates in mice. Scientific reports, 2018. 8(1): p. 15351.

https://www.nature.com/articles/s41598-018-33619-0

2. Perry, R.J., et al., Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature, 2016. 534(7606): p. 213

3. Triantafyllou, K., C. Chang, and M. Pimentel, Methanogens, methane and gastrointestinal motility. Journal of neurogastroenterology and motility, 2014. 20(1): p. 31.

4. Petersen, L.M., et al., Community characteristics of the gut microbiomes of competitive cyclists. Microbiome, 2017. 5(1): p. 98.

5. Cakmak, Y.O., Provotella‐derived hydrogen sulfide, constipation, and neuroprotection in Parkinson’s disease. Movement Disorders, 2015. 30(8): p. 1151-1151.

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We know that high-energy food (rich in refined sugars and fats) is addictive and can lead to an eating addiction and obesity. Addiction is a very severe disorder with chronic and relapsing components. People who suffer from addiction show compulsivity, persistence to seek the reward (food), and high motivation to overconsume in some cases.

Food Addictions in People and MiceTo study eating addiction, we have developed a mouse model that shows persistence to eat, high motivation for palatable food and resistance to punishment in obtaining the food. We have tested these three characteristics in several genetically identical animals and selected two extreme groups: Mice that are vulnerable to eating addiction and mice that are resilient to it.

Mice have more than 25,000 genes in their genome, and they can be turned on or turned off (‘expressed’ or ‘not expressed’) depending on certain needs or circumstances.

We are now investigating the activation status of a certain type of genes, the ones encoding the so-called microRNAs that are very important as they are involved in regulating the function of other genes. An alteration in the status of one of these genes can have numerous downstream consequences.

In particular, our studies highlighted several microRNA genes that are involved in multiple brain functions, like synaptic plasticity (variation in the strength of nerve signaling) or neuronal development. Now we will test these alterations in patients to try to find convergent abnormalities.

All this work is being done at the Department of Genetics, Microbiology & Statistics (Universitat de Barcelona) and at the Neuropharmacology lab at the Universitat Pompeu Fabra, both based in Catalonia.

Co-authored by Bru Cormand, Judit Cabana, Noelia Fernàndez

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