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“The chronic disease epidemic in industrialized societies has been paralleled by the rapid ‘‘westernization’’ of the microbiota in developing countries.”

There is growing consensus that the epidemic of non-communicable chronic diseases, including metabolic syndrome, cardiovascular disease, Parkinson and Alzheimer disease and colon cancer are largely driven by chronic systemic immune activation. The epidemic has gradually unfolded during the past 75 years with accelerating industrialization affecting food production and processing, and dramatically changing lifestyles. As I have discussed in detail in The Gut Immune Connection, while an increasing percentage of the US population has gotten sicker from these diseases, the enormous healthcare expenditures thrown at these problems in the form of colon cancer screening, coronary bypass surgery, blood pressure and cholesterol medications is keeping people alive and functional and has even led to an increase in life expectancy. The chronic disease epidemic in industrialized societies has been paralleled by the rapid ‘‘westernization’’ of the microbiota in developing countries and in US immigrants coming from other parts of the world, with reduction and loss of microbial functions and taxa accompanied by deteriorating, markers of host health, obesity and rising inflammatory markers typical in industrialized populations.

Changes in dietary habits, in particular a reduction in the ratio between plant-based (a variety of fresh fruits and vegetables) and animal-based (meat, dairy, and eggs) paralleled by a decrease in the consumption of dietary fiber, and an increase in the amount of ultra-processed foods with high sugar/low fiber content and chemical additives have been identified as a major factor in these global changes in health. In addition to the low consumption of fermented foods, the decrease in the amount and variety of dietary fiber (referred to as microbiota-accessible carbohydrates (MACs)) in the diet has generally been considered an important cause of the decrease in diversity and richness of the gut microbiota, and even the loss of certain taxa.

“While there has been a significant increase in the popularity of probiotic supplements and pills, the consumption of a wide variety of fermented foods has been lagging behind.”

Another less often mentioned aspect of the standard American diet (SAD) when compared to Asian or European diets is the limited consumption of naturally fermented foods, such as fermented dairy products, Kimchi, Kombucha or Sauerkraut which contain microorganisms often – and falsely referred to as probiotics. Fermented foods are those made through colonization of food components with microbes and resulting enzymatic conversion. Live microbes present in traditional fermented foods and beverages such as kombucha, yogurt, kefir, sauerkraut, kimchi, and many pickled foods typically do not meet the required evidence level for probiotics (“live microorganisms which when administered in adequate amounts confer a health benefit on the host”). While there has been a significant and continuing increase in the popularity of probiotic supplements and pills, the consumption of a wide variety of fermented foods as part of the regular American diet has been lagging.

In view of our incomplete understanding of the complexity of the gut microbiome and the absence of specific non-dietary interventions as treatment options for the most common chronic diseases, the integration of the gut microbiota into human biology, and dietary manipulation of gut microbes has the potential to improve many aspects of human health. Despite growing promotion in the media and by functional medicine practitioners of “anti-inflammatory diets”, a key question for scientists is whether diets that target the gut microbiome by increasing its diversity and richness can attenuate systemic inflammation in healthy individuals (not only in cells or mouse models) and reduce the prevalence of some of our most common diseases. Another question is whether there are broad, non-personalized dietary recommendations based on microbiota-host interactions for improved health across populations.

“…the study aimed to determine what role a diet high in fiber compared to a diet high in fermented foods play in gut microbial composition and function, as well as in the presence of systemic inflammatory markers.”

I have recently reviewed the pivotal study from the Sonnenburg Lab at Stanford University (Wastyk et al. Cell 2021;184:1-17) which was published the prestigious scientific journal Cell. They reported results from a well-designed study that aimed to determine what role a diet high in fiber compared to a diet high in fermented foods play in gut microbial composition and function, as well as in the presence of systemic inflammatory markers.

The investigators used a 17-week randomized, prospective study (18 participants per study arm) combined with measurement of many microbiome parameters and inflammatory markers in the blood to identify diet-specific effects. Blood and stool samples were collected longitudinally along a 3-week baseline period, followed by a 4- week ramp up phase during which participants gradually increased intake of their respective diets, then a 6-week maintenance phase where they maintained a high level of consumption of either fiber or fermented foods, and finally a 4-week “choice” period where they could maintain their respective diet to their desired extent. While participants’ gut microbiota at baseline did not differ between the two arms, both groups successfully increased their consumption of fiber or fermented foods respectively.

Fiber-rich foods were categorized into fruits, vegetables, legumes, grains, nuts and seeds, and other, and total fiber consumption increased from an average of 21.5 ± 8.0 g per day at baseline to 45.1 ± 10.7 g per day at the end of maintenance phase. (The American Heart Association recommends a daily fiber intake of 25-30 g/day, while the actual intake among adults in the United States averages a mere 15 grams a day). Fermented foods were grouped into yogurt, kefir, fermented cottage cheese, fermented vegetables, vegetable brine drinks, kombucha, other fermented non-alcoholic drinks, and other foods and total fermented food consumption increased from 0.4 to 6.0 servings per day.

“The high fiber diet did not increase microbial community diversity and richness, and even more surprising, inflammatory markers in the high fiber group on average remained unchanged.”

There is extensive preclinical and clinical evidence that a fiber rich diet is associated with increased gut microbial richness and diversity, in particular of microorganisms that have the enzymes to break down complex carbohydrates or MACs into short chain fatty acids, in particular butyrate (Sonnenburg ED and Sonnenburg JL. Cell Metab 2014;20:779-86). Butyrate has anti-inflammatory effects mediated by specific receptors on cells in the gut-associated immune and endocrine systems and throughout the body. As expected, the high fiber diet shifted the MAC-processing capacity and metabolic output of the microbiota, as reflected by the increase in these microbiota-produced fiber metabolizing enzymes. However, surprisingly, the increase in fiber metabolizing enzymes was not paralleled by an overall increase microbial community diversity and richness, and even more surprising, a battery of inflammatory markers in the high fiber group on average remained unchanged. However, the study identified subgroups of individuals based on their baseline, pre-study microbiome composition, and these subgroups included two low inflammation and one high inflammation cluster. The low inflammation group showed higher microbial diversity compared to the high inflammation group, as well as greater prevalence of beneficial microbes including Coprococcus, Ruminococcus and Anaerostipes, whereas Akkermansia was enriched in the high inflammation cluster. These findings were consistent with an earlier study which demonstrated that a dietary intervention of increasing soluble fiber, was less effective in reducing markers of systemic inflammation in individuals with lower microbiome richness. In other words, if you don’t have the required microbes to break down the fiber molecules into beneficial metabolites, the benefits of a plant-based diet may be less than if you start out with a diverse population of microbes.

“… the observed increased diversity in the fermented food group likely involved gut ecosystem remodeling rather than an immediate reflection of consumed quantities of microorganisms.”

On the other hand, the high-fermented-food diet steadily increased microbiota diversity and decreased systemic levels of inflammatory markers. Interestingly, the observed increase in microbiota diversity in the high-fermented-food-diet arm was not primarily due to the microbes consumed with the fermented food (as is commonly assumed), but rather a result of shifts in or even new additions to the existing microbial ecosystem. These findings suggest that the regular consumption of fermented foods has an indirect effect on microbiota diversity and different from the effects of fiber, apparently overcoming the colonization resistance of the microbial ecosystem and rendering it receptive to the incorporation or increased representation of previously undetected strains within the gut. Remarkably, and contrary to the well-known observation that ingested probiotic supplements disappear from the gut within 48 hours after stopping the probiotic pill intake, this diversity increase was sustained during the study period when participants were allowed to choose the number of fermented foods (“choice” period), when fermented food intake was higher than baseline but lower than at the end of maintenance. These findings strongly suggest that increased diversity likely involved gut ecosystem remodeling rather than an immediate reflection of consumed quantities of microorganisms contained in the fermented food diet.

“As fermentation of food has been practiced for tens of thousands of years, consuming fermented foods may offer an effective way to reintroduce evolutionarily important interactions between the gut and its microbiome.”

Fermented foods which have been a regular component of diets in most parts of the world (kombucha, fermented dairy products, kimchi, and Sauerkraut) have only recently gained popularity in the US as reports of potential health benefits in animal models and humans have emerged (Dimidi et al., 2019; Villarreal-Soto et al., 2020). Several studies have linked the consumption of fermented foods with weight maintenance and decreased risk for non-communicable chronic diseases. A recent longitudinal study of a subset of American Gut Project participants found differences in microbiota composition and fecal metabolome among fermented food consumers versus non-consumers (Taylor et al., 2020). As fermentation of food has been practiced to conserve food for tens of thousands of years, giving our human genes sufficient time to adapt to fermentation-associated microbes, consuming fermented foods may offer an effective way to reintroduce evolutionarily important interactions between the gut and its microbiome.

Before making premature conclusions about the relative health benefits of a fermented food-rich diet over a fiber-rich diet, several potential limitations of the study need to be considered. Importantly, high-fiber consumption did appear to increase stool microbial carbohydrate-degrading capacity, and altered short chain fatty acid production, indicating that fiber induced microbiome remodeling and change in function was occurring within the study time frame, but this was not accomplished through an increase in gut microbial composition. The study did not contain a control group without any dietary intervention, and the number of participants in each study arm was limited. Furthermore, participants in the high fiber group started out with a higher average fiber consumption than the US population. The two study groups may have differed in other factors that are known to influence the gut microbiome, such as physical exercise, stress and emotional factors and sleep.

Furthermore, there appear to be subsets of individuals with a unique gut microbial composition which respond differently to a high fiber diet intervention. As suggested by the authors, it is possible that the relatively short duration of the study was not sufficient to allow for the recruitment of new taxa to the microbiota in the high fiber diet group, which could be an indication that exposure to new microbes was limited within the urban environment of participants, due to increased hygiene, less exposure to microbes from soil and animals, and limited sharing of microbes between individuals. Fiber-induced microbiota diversity increases may be a slower process than fermented food induced increases, requiring longer than the 6 weeks of sustained high consumption achieved in this study.

“What are the conclusions of this and previous studies for the health-conscious consumer?”

What are the conclusions of this and previous studies for the health-conscious consumer, navigating through the jungle of recommendations for the most effective “anti-inflammatory” diet and the best cocktail of probiotic supplements?

1. A regular diet high in a variety of plant-based and in fermented foods is optimal for the health of the gut microbiome, a reduction of systemic immune activation and a reduction of some of the most common chronic diseases.
2. An increase in the regular intake of a variety of fermented foods has a rapid and persistent beneficial effect on the health of the gut microbiome and on systemic immune function.
3. It is conceivable that the combination of a diet rich in fermented foods (causing persistent increases in richness and diversity), with a diet rich in varied plant-based products (increasing MAC production) results in a synergistic effect on reducing systemic immune activation.
4. Consuming your cocktail of pro and prebiotic supplements while consuming the Standard American Diet, depleted in fiber and fermented foods, is unlikely to give you the health benefits that you strive for, while the addition of evidence-based pre and probiotic supplements to a healthy largely plant-based diet, may be the best way to improve your gut microbiome and reduce systemic inflammation.

* This post was originally published on July 27, 2021 and has been updated with new information.