The anti-inflammatory effects of fermented foods

Research in recent years has clearly shown that the hundreds of billions of bacteria that colonize our digestive system (what we call the microbiota) play several very important functions in maintaining good health. The essential role of intestinal bacteria is mainly linked to their fermentation activity: in the absence of oxygen (as is the case in the colon), microbial metabolism uses molecules that have resisted digestion (dietary fibre, for example) as a source of energy and at the same time produces several metabolites that can greatly influence several physiological parameters, both at the level of the intestine and of the organism as a whole.

The nature of what we eat has a huge influence on the type of bacteria that make up the microbiota and, consequently, on the different compounds that are produced by the fermentation activity of intestinal bacteria. This is particularly evident when comparing the effects of a diet known to have beneficial effects on health (rich in plants with little or no animal-based foods) with those of a Western-style diet (rich in meat and ultra-processed foods, but deficient in plants), which is associated with an increased risk of several chronic diseases (Figure 1). While a high intake of plants (and therefore fibre) allows the establishment of a diversified microbiota, whose fermentation activity generates several molecules essential for the adequate control of metabolism, in particular short-chain fatty acids (SCFA) and certain peptides such as GLP-1 (the molecule that led to the discovery of the anti-obesity agents Ozempic and Mounjaro), fibre deficiency forces the microbiota to turn mainly to proteins and fats as a source of energy and leads to the production of several molecules that destabilize the intestinal mucosa (see the legend of Figure 1 for more details on the phenomena involved).

Figure 1. Influence of diet on microbiota composition and activity and its impact on metabolism. A. Establishing a healthy microbiota, characterized by a high diversity of bacterial species, typically requires a diet high in plant fibre and low in animal fats and proteins. Indigestible complex carbohydrates (polysaccharides) are metabolized by the large intestinal microbiota and fermented to produce a wide range of compounds and promote the formation of a thick protective mucus layer. Microbial production of short-chain fatty acids (SCFAs) provides an additional energy source for intestinal cells (colonocytes) and causes a decrease in pH that favours the growth of beneficial species. SCFAs (acetate, butyrate, and propionate) can also bind to certain receptors to stimulate the secretion of GLP-1 (glucagon-like peptide-1) and peptide YY (PYY), two molecules that contribute to an increase in energy expenditure, a reduction in food intake, and an improvement in glucose metabolism and insulin secretion. Butyrate is also metabolized by β-oxidation (the fatty acid degradation pathway) in intestinal cells, and this oxygen consumption helps maintain an optimal anaerobic environment for the survival of several beneficial bacterial species. B. A diet rich in animal-based foods and ultra-processed products, but low in fibre (like the modern Western diet), induces an imbalance in the composition of the microbiota (dysbiosis). Fibre scarcity forces bacteria to turn to protein breakdown products (peptides and amino acids) and fats as an energy source, which generates several by-products of fibre breakdown such as branched-chain fatty acids (BCFAs) (such as 2-methyl butyrate, isobutyrate, and isovalerate), amines (such as trimethylamine, which can be converted to TMAO, a proatherogenic molecule), malodorous gases (H₂S), and traces of phenols, indoles, and ammonia. Combined with decreased SCFA production, these molecules increase colonic pH and promote the production of secondary bile acids, a risk factor for cancer. Overall, these changes in the microbial environment cause a loss of mucus layer tightness that allows certain molecules from pathogens (e.g. lipopolysaccharides (LPS)) to come into contact with immune cells and thus trigger a low-grade systemic inflammatory response. This inflammation, combined with a reduction in GLP-1 and PYY levels caused by the decrease in SCFA production, can induce insulin resistance and an increase in blood glucose. Adapted from Fan and Pedersen (2021).

One of the main consequences of this disruption of the microbiota balance by the modern Western diet is the creation of conditions conducive to the development of a chronic inflammatory climate. This is well highlighted by certain studies that have examined the impact of a drastic change in the eating habits of certain populations. A good example comes from a study that compared the effect of the typical diet of African-Americans to that of inhabitants of rural areas of Africa (the two populations have common origins, which minimizes the influence of genes on the observed effects). For two weeks, 20 African volunteers consumed a typical American diet (high in fat and low in fibre), while 20 African-American volunteers were given an African diet (high in plants and fibre and low in fat). The results are quite spectacular: for the Africans, eating like a typical American quickly led to a major change in their intestinal health, with a loss in the diversity of beneficial bacteria and an increase in inflammation. Conversely, African-Americans, whose colons were in poor health to begin with (presence of polyps, inflammation, pathogenic bacteria), saw their condition improve very quickly by eating more fibre, with an increase in microbiota diversity and a reduction in mucosal inflammation. Another study of Southeast Asian refugees living in America (the Hmong of Laos and the Karen of Myanmar) also showed a marked decline in the diversity of the microbiota of these immigrants, with a particular decrease in the bacteria involved in the digestion of fibre and an increase in those that contribute to inflammation.

In short, if a diet rich in plants is superior to one based on a high intake of animal products, it is largely because it provides optimal conditions for the metabolism of intestinal bacteria. Microbial strains well adapted to these conditions tend to outnumber other members of the community, which leads to changes in the overall composition of the microbial community and positively selects bacteria that generate a wide range of products with several positive impacts on health, particularly in terms of reducing chronic inflammation.

Fermented products: a food microbiota
The fermentation process at work in the intestine is comparable to that used for thousands of years by humans to produce a very large number of fermented foods, whether alcoholic beverages (wine, beer), milk derivatives (yogurt, cheese, kefir), various vegetable preparations (sauerkraut, kimchi), or legumes (miso, tempeh). All these foods (and several hundred others, depending on the culinary cultures of different countries) have in common the fact that they are the result of the fermentation activity of one or more microorganisms that modify the composition of the original food and generate a new product, with new properties:

• Increased shelf life through the microbial production of organic acids, antibacterial substances, or ethanol.
• Creation of new flavours and textures that allow for diverse dining experiences.
• Increased nutritional value and quality of food through the production of bioactive molecules (vitamins, phytochemicals, bioactive peptides).
• Modifications to the food matrix that make foods more digestible, for example by reducing the levels of certain less digestible molecules (lactose for intolerant people) or by eliminating certain toxins.
• Presence of live microorganisms (probiotics) that can positively influence the function of the gut microbiota.

Historically, fermentation has been mainly used to improve the shelf life of foods: the production of acids (lactic, acetic, propionic), bacteriocins (peptides with antibacterial properties), or ethanol by microbial metabolism reduces the risk of contamination by various opportunistic microorganisms and helps maintain food safety over longer periods. However, beyond this preservation function, increasing evidence indicates that fermentation also leads to changes in food composition that can have several positive health benefits (Figure 2).

Figure 2. Mechanisms involved in the health benefits of fermented foods. In addition to the nutritional contributions of the basic constituents of these foods (proteins, carbohydrates, lipids), several fermented foods contain live microorganisms (probiotics) that are resistant to stomach acidity and can temporarily integrate the microbiota and increase its diversity. The transformation of foods by fermentation can also lead to an improvement in their nutritional value (for example, through the synthesis of vitamins) as well as the generation of biologically active compounds called postbiotics (bioactive peptides, polyphenols, organic acids, oligosaccharides). The interaction of these compounds with the intestinal microbiota, the intestinal epithelium, or the host immune system (dendritic cells, lymphocytes, macrophages) can positively modulate several physiological parameters. Adapted from Marco et al. (2021).

This is particularly true for certain fermented foods that contain live microorganisms, commonly called probiotics: at the beginning of the 20th century, the Ukrainian biologist Elie Metchnikoff (Nobel Prize in Medicine in 1908) suggested that the high consumption of yogurt rich in certain lactobacilli (Lactobacillus delbrueckii) was responsible for the exceptional longevity of the population living in the Balkans compared to that of the inhabitants of other European countries. A high intake of probiotics is certainly not the only phenomenon responsible for this increase in life expectancy, but the fact remains that a large number of studies carried out since that time suggest that the regular consumption of foods containing probiotics could indeed play an important role in maintaining good health.

Many studies (see here and here, for example) have shown that microorganisms present in fermented foods can survive the acidic conditions of the stomach and reach the colon where they can represent up to 1% of the local bacteria, depending on the type of bacteria and dietary habits. Although it is unlikely that these microorganisms from fermented foods will establish themselves long-term in the intestine, they are nevertheless metabolically active and short-term colonization could therefore be sufficient to synthesize bioactive compounds beneficial for health, especially if fermented foods are consumed regularly.

The positive influence of fermented foods on the composition and function of the microbiota could have important repercussions on immune function. Approximately 70% of the cells of the human immune system are located in the digestive system, and it is well established that the microbiota plays an absolutely essential role in the formation and proper development of these cells, both for the innate immune system (macrophages, among others) and the adaptive immune system (B and T lymphocytes). Repeated exposure to microorganisms present in fermented foods could therefore help “educate” the immune system to develop the ability to distinguish microorganisms that must be tolerated (such as beneficial bacteria) from those that must be eliminated (pathogens, viruses, protozoa, etc.). The deficiency in fermented foods, typical of the diet of most industrialized countries, could therefore harm the optimal development of immunity and thus increase the risk of inappropriate immune reactions such as chronic inflammation and autoimmune diseases.

Anti-inflammatory effects
A recent study suggests that the beneficial effects of fermented foods on the microbiota and inflammation may even be greater than those associated with a high-fibre diet.

The study, called FeFiFo (for Fermented and Fibre-rich Food), involved 36 healthy individuals divided into two groups. The researchers asked one group to increase their fibre intake, while the other group was asked to increase their fermented food intake. The study was divided into four phases: a 3-week pre-intervention phase (to serve as a baseline), a 4-week phase during which individuals began to increase their consumption of their respective foods, a 6-week phase during which individuals maintained a high consumption of their respective foods, and a 4-week phase during which individuals consumed whatever they desired.

Analysis of blood and fecal samples collected throughout these phases revealed that the addition of fermented foods caused a significant increase in bacterial diversity and a parallel reduction in several markers of inflammation. Interestingly, this increase in diversity does not appear to be due to the consumption of microbes from fermented foods, as the percentage of bacteria in the microbiota from these fermented foods remained below 6% throughout the study. Rather, it appears that the consumption of these fermented foods promoted the establishment of new members of the microbial community that were previously underrepresented.

In this study, the positive effects of fermented foods on microbial diversity and inflammation reduction were greater than those observed following an increase in fibre intake, possibly because the duration of the study was not long enough for the changes in the microbiota induced by fibre to become significant enough to be detected. Regardless, the results of this study clearly show that the addition of fermented products to one’s diet represents a rapid and effective way to improve the composition and function of the microbiota and reduce chronic inflammation.

Cardiovascular effects
Chronic inflammation is a major risk factor for all chronic diseases, particularly cardiovascular diseases, suggesting that regular consumption of fermented foods may positively influence heart and vascular health.

Most studies that have looked at this issue have examined the impact of dairy products such as yogurt and cheese, the main fermented foods consumed by Western populations.

In a meta-analysis of 29 prospective cohort studies involving nearly 1 million participants, total dairy consumption was found to have no significant impact on total mortality or cardiovascular disease incidence, consistent with several data showing that milk can be considered a “neutral” food, with no major positive or negative effects. On the other hand, consumption of fermented dairy products (mainly cheese, as well as yogurt) was associated with a slightly lower risk (about 5% for each 50 g daily portion) of total mortality and cardiovascular disease. The Prospective Urban Rural Epidemiology (PURE) study, involving 136,384 participants across 21 countries and 5 continents, showed that higher consumption of total dairy products (>2 portions/day versus none) was associated with a significantly lower risk (16%) of cardiovascular disease, with this effect being largely related to yogurt consumption. Similar cardioprotective effects associated with dairy consumption have also been observed in studies from Finland and Australia. High combined consumption of fermented dairy products has also been associated with reduced body weight as well as a lower risk (15%) of diabetes, two important risk factors for cardiovascular disease.

Back to the roots
Although the underlying mechanisms remain to be better understood, the data that are currently available suggest that the inclusion of fermented products in one’s diet can provide health benefits, particularly in terms of reducing chronic inflammation. In a way, this is a simple way to compensate for the major loss of microbial diversity caused by the many changes to our lifestyle over the last few centuries, in particular increased hygiene, widespread use of antibiotics, consumption of sterile processed foods, and urban life without close contact with nature. The analysis of ancient excrement residues dating back 2,000 years or from indigenous populations with a traditional lifestyle indicates that the composition of our current microbiota is very different and much less diverse. It has been proposed that the disappearance of certain bacterial strains with essential roles in the control of metabolism and immunity could be contributing to the increase in several chronic diseases currently affecting people in rich countries. Restoring at least part of this microbial diversity by consuming fermented foods could therefore mitigate the negative impact of the modern lifestyle causing a high incidence of these diseases.