How to eat healthy? Consider that you are also feeding your microbes!

Author: Prof Jens Walter, Principal Investigator, APC Microbiome Ireland, University College Cork

Many of us want to eat healthy for a variety of reasons; to shed extra pounds, to get more fit and energetic, and, most importantly, to live a long and healthy life without chronic diseases. However, how to eat healthy is no simple task. There is an uncountable amount of nutrients to focus on and foods to choose from, and these food components do not work in isolation. If you lower your carbohydrate intake, you do this by eating either more fat or protein, which will then have its own short- and long-term consequences for health. Contemporary nutrition research is, therefore, increasingly focused on whole diets and dietary patterns. But here again, the question of which diet is most beneficial is not an easy one to answer, as the effects of different diets are multi-facetted and long-term effects are often insufficiently understood. Effects further differ among individuals depending on their genetic predisposition, physiological state, and health status. There are hundreds of different opinions on the internet on what constitutes a healthy diet. Even among nutrition experts disagreements remain, exemplified for example by the controversial scientific debates around the ‘Carbohydrate Insulin Model’ in causing obesity, or the value of classifying foods according to the degree by which they are processed to combat obesity.

Healthy Eating from a Microbiome Perspective

In my (very biased) opinion, the gut microbiome can provide an important perspective in our quest for what constitutes a healthy diet. Throughout my career as a microbiome researcher, I was exposed to and inspired by work that established the important health implications of interactions between diet and the gut ‘microflora’ (what it was called in the day). Early in my career, I became intrigued by older studies that linked the low prevalence of colon cancer in Japan when compared with the USA to detrimental effects of the western diet on the microflora. Interestingly, colon cancer rates in Japanese immigrants to the US were just as high as in other Americans, and Japan has since seen a steep rise in colon cancer over the last 50 years with the introduction of western fast food. Already 50 years ago, scientists implicated interactions between gut bacteria and saturated animal fat in the development of colon cancer, a connection that has since been validated. A little bit later, work by Ian Rowland and others established how metabolic activities of the gut ‘microflora’, and its toxic and carcinogenic metabolites, can cause colon cancer. This work demonstrated, among other things, that dietary fat and the bacterial fermentation of proteins results in detrimental metabolites, while saccharolytic fermentation is beneficial. These findings remain highly relevant as it is possible to reduce the negative effects of proteolytic fermentation by supporting saccharolytic fermentation with dietary fibre (through lowering the pH), connections nicely summarised more recently by Katri Korpela.

Advancing Healthy Eating through the Microbiome

After 2000, the ‘microflora’ became the ‘microbiota’ and then the ‘microbiome’, and the field virtually exploded. In the lab of Jeffrey Gordon, work by Fredrik Bäckhed and Peter Turnbaugh established how pathologies in diet-induced obesity models were microbiome dependent, and Ruth Ley showed that the evolution of mammals was profoundly impacted by diet-microbiome-host interactions. In Scotland, Harry Flint and colleagues elucidated the mechanisms by which dietary fibre and other food components impacted microbiota composition and metabolism. Using human nutritional trials, the group established that low-carbohydrate, high-protein diets led to high levels of amino acid fermentation with increased concentrations of detrimental metabolites (such as N-nitrosamines), suggesting a less favourable gut environment with respect to colon cancer risk. Work from several other groups established that the bacterium Bilophila (which, as the name implies, ‘loves’ bile) was the causal link between saturated fat and gut inflammation. The Sonnenburg lab and several other research groups showed that refined modern diets are evolutionary misaligned with the human gut microbiome. Low intake of dietary fibre essentially starves the microbiome, reducing microbiome diversity and forcing microbes to target mucins to satisfy their nutritional needs, leading to the degradation of the mucus layer in the gut. This reduces the integrity of the mucosal defence and results in microbial encroachment to the intestinal lining, inflammation, and several immunological and metabolic pathologies in mice. Many research groups, some from the APC Microbiome Ireland, have contributed to this important research area and established the importance of diet to maintain a ‘healthy’ gut microbiota. Together with several acclaimed nutrition researchers, I have recently published a review on what we think constitutes healthy eating from a microbiome perspective in the journal Cell Host & Microbe that is available open access: https://pubmed.ncbi.nlm.nih.gov/35679823/. We also published a lay article with the Biocodex Microbiota Institute that is freely available: https://www.biocodexmicrobiotainstitute.com/en/pro/gut-microbiome-determinant-healthy-eating. I refer interested readers to these resources, but in summary, national dietary guidelines from around the world, such as Canada’s Food Guide and the Healthy Eating Guidelines in Ireland, provide consistent dietary recommendations that are overall microbiome compatible.

Diet-Microbiome Interactions and Nutrition Controversies

However, some inconsistencies exist between dietary recommendations, as well as some controversies within the nutrition literature. We argue that a mechanistic understanding on diet-microbiome interactions can inform discussion of nutrition controversies and advance healthy eating. For example, there are inconsistencies and controversies on the inclusion of dairy products in a healthy diet and the strict exclusion of processed meats. As I write above, there is a long history of microbiome research that links saturated animal-based fats with carcinogenic metabolites and pro-inflammatory microbes (e.g. Bilophila). Microbiome research, therefore, supports a stricter exclusion of animal-based saturated fat, meaning the strict exclusion of processed meats and a reduction of high-fat dairy products such as butter, cream, and cheese. Lower fat varieties are likely beneficial, especially when fermented (e.g. yoghurt). Findings from microbiome research also caution the long-term use low-carb, high protein and fat diets, as their effects on gut microbiota metabolism are likely detrimental. Microbiome-based considerations also suggest that there might be value in going beyond what is recommended in dietary guidelines for some nutritional components. For example, given that humans and their microbiomes have evolved with very high amounts of dietary fibre, it is likely beneficial to consume dietary fibre at levels higher than the 25-38 grams of fibre that are currently recommended in dietary guidelines.

‘Eat food. Not too much. Mostly plants.’

Obviously, what constitutes a healthy diet is complex, and this blog can only provide some simple and likely oversimplified recommendations. It is also important to consider that the effect of diet will depend on the physiological state and health of an individual, might differ between geographic locations and human cultures, and patients often require specialized diets. Furthermore, most studies show substantial inter-individual variation in how humans respond to diet. The gut microbiome is likely to contribute to some of this variation, which is an area of active research, and several companies are now offering personalized nutrition advise based on microbiome analyses. The jury is still out on the value of such personalized dietary advice based on microbiome configurations. However, from the limited amount of publications in this space, I would conclude that in healthy individuals, the beneficial effects of plant-rich diets recommended in most dietary guidelines, which are quite consistent among trial participants, are relatively larger than what has been shown for personalized dietary advice. I would say that if one were looking for a simple rule to follow, microbiome science as a whole is in support of Michael Pollan’s seven-word advice on healthy eating: ‘Eat food. Not too much. Mostly plants.’ So simple, but so hard to do!