What we eat affects the microbes that call our guts home and these in turn modulate our immune defenses. Our lifestyles in urban, industrialized societies are resulting in decreases in the diversity of our gut microbiomes and increases in inflammatory diseases.

“Gut inflammation and decreased gut microbial diversity are linked to stress, alcohol, and high-sugar diet among other causes. Low microbial diversity leads to an increase in gut permeability (aka leaky gut), which increases influx of lipopolysaccharide (aka endotoxin) from the gut. Studies have shown that a rise in circulating endotoxin levels precedes metabolic syndrome, weight gain, eventually leading to an elevated BMI with obesity, and diabetes,” said Vincent M. Pedre, MD, medical director of Pedre Integrative Health and author of the book Happy Gut.

Researchers at the Stanford School of Medicine have conducted a multiomics-based clinical trial to compare the effects of two dietary interventions—plant-based fiber and fermented foods—on the gut microbiome and the immune system in healthy adults.

Their findings published in the Cell article, “Gut-microbiota-targeted diets modulate human immune status,” showed fermented foods, more so that high-fiber foods, can increase gut microbial diversity and decrease gut inflammations.

Financial support for the study came from donations to the Center for Human Microbiome Research, Paul and Kathy Klingenstein, the Hand Foundation, Heather Buhr and Jon Feiber, Meredith and John Pasquesi, the National Institutes of Health, a Stanford Dean’s Postdoctoral Fellowship, a National Science Foundation Fellowship, the Institute for Immunity, Transplantation and Infection, and the Sean N. Parker Center for Allergy and Asthma Research.

In the clinical trial, 36 healthy adults were randomly assigned to a 10-week diet that included either fermented or high-fiber foods. The researchers analyzed blood and stool samples collected during a three-week pre-trial period, the 10 weeks of the diet, and a four-week period after the diet when the participants ate as they chose.

The trial shows eating foods such as yogurt, kefir, fermented cottage cheese, kimchi, fermented vegetables, vegetable brine drinks, and kombucha increases overall microbial diversity, with larger servings rendering stronger effects.

“This is a stunning finding,” said Justin Sonnenburg, PhD, associate professor of microbiology and immunology and senior investigator on the study. “It provides one of the first examples of how a simple change in diet can reproducibly remodel the microbiota across a cohort of healthy adults.”

Immune profiling studies that are part of the outcome parameters in the study show decreased activation of four types of immune cells in the fermented-food group along with decreased blood levels of 19 inflammatory proteins, including interleukin 6 (IL6) that is linked to rheumatoid arthritis, type-2 diabetes, and chronic stress.

“Microbiota-targeted diets can change immune status, providing a promising avenue for decreasing inflammation in healthy adults,” said Christopher Gardner, PhD, the Rehnborg Farquhar professor, director of nutrition studies at the Stanford Prevention Research Center, and co-senior author on the study. “This finding was consistent across all participants in the study who were assigned to the higher fermented food group.”

A high-fiber diet rich in legumes, seeds, whole grains, nuts, vegetables and fruits, did not decrease any of the 19 inflammatory proteins included in the study nor did it alter gut microbial diversity.

“We expected high fiber to have a more universally beneficial effect and increase microbiota diversity,” said Erica Sonnenburg, PhD, a senior research scientist in basic life sciences, microbiology, and immunology and co-senior author on the study. “The data suggest that increased fiber intake alone over a short time period is insufficient to increase microbiota diversity.”

Hannah Wastyk, a PhD student in bioengineering and Gabriela Fragiadakis, PhD, former postdoctoral scholar who is now an assistant professor of medicine at UC-San Francisco are co-first authors on the study.

Gardner said that a low microbiome diversity has been linked to obesity and diabetes. “We wanted to conduct a proof-of-concept study that could test whether microbiota-targeted food could be an avenue for combatting the overwhelming rise in chronic inflammatory diseases.”

While high-fiber diets have been associated with lower rates of mortality, fermented foods can help with weight maintenance and may decrease the risk of diabetes, cancer, and cardiovascular disease, earlier studies show.

The study shows on one hand that increasing consumption of fermented foods can rapidly alter the gut microbiome in the short-term and on the other hand, the limited change in the microbiome in the high-fiber group demonstrates a resilience of the human microbiome over short time periods.

The results also showed that greater fiber intake led to more carbohydrates in stool samples, pointing to incomplete fiber degradation by gut microbes. These findings are consistent with other research suggesting that the microbiome of people living in the industrialized world is depleted of fiber-degrading microbes. Despite stable microbial community diversity, the high-fiber diet increased microbiome-encoded carbohydrate active enzymes (CAZymes) that degrade glycans.

“It is possible that a longer intervention would have allowed for the microbiota to adequately adapt to the increase in fiber consumption,” said Erica Sonnenburg. “Alternatively, the deliberate introduction of fiber-consuming microbes may be required to increase the microbiota’s capacity to break down the carbohydrates.”

“There are many more ways to target the microbiome with food and supplements, and we hope to continue to investigate how different diets, probiotics and prebiotics impact the microbiome and health in different groups,” said Justin Sonnenburg.

The researchers also plan to conduct studies in mice to investigate the molecular mechanisms by which diets alter the microbiome and reduce inflammatory proteins, and test whether high-fiber and fermented foods synergize to influence the microbiome and immune system of humans. Another goal of the team is to examine whether the consumption of fermented food decreases inflammation or improves other health markers in patients with immunological and metabolic diseases, and in pregnant women and older individuals.

“The most important takeaway from this Stanford Study on dietary interventions and their effects on the gut microbiome is that in western societies with increased inflammation and loss of microbial diversity (due to overexposure to antibiotics, among other medications), a fermented foods diet (more so than a fiber-rich diet, which was previously believed) may be more valuable in countering these effects. This can translate into dietary recommendations that can move the needle in a positive direction for the millions of people suffering from inflammation and loss of microbial diversity,” said Pedre, who is unrelated to the current study and comments as an independent expert.

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