Humans are the only species that cook their food, and studies in mice and in humans by scientists at the University of California, San Francisco (UCSF), and Harvard University have now shown for the first time that eating raw vs cooked food can have a fundamental impact on the microbial communities that naturally live in the gut. The researchers suggest that their results could have implications for strategies to optimize microbial health, and also provide new insights into how cooking may have altered evolution of the gut microbiome during human prehistory.

“It was exciting to see that the impact of cooking we see in rodents is also relevant to humans, although interestingly, the specifics of how the microbiome was affected differed between the two species,” commented Peter Turnbaugh, PhD, an associate professor of microbiology and immunology and a member of the executive leadership of the UCSF Benioff Center for Microbiome Medicine. “We’re very interested in doing larger and longer intervention and observational studies in humans to understand the impact of longer-term dietary changes.” Turnbaugh and colleagues reported their findings in Nature Microbiology, in a paper titled, “Cooking shapes the structure and function of the gut microbiome.”

Diet outweighs even host genetics as a “critical determinant” of variation in the structure and function of our gut microbiota, the authors explained. Studies over recent years have demonstrated that many aspects of human health are influenced by the ecological health of the microbial communities that live in and on us. However, they continued, while researchers are working to better understand how our environments and behaviors can impact on and encourage healthier microbiomes, the effects that cooking might have on how diet impacts microbiome structure and function hasn’t been investigated to any degree.

“Our lab and others have studied how different kinds of diet—such as vegetarian versus meat-based diets—impact the microbiome,” said Turnbaugh. “We were surprised to discover that no one had studied the fundamental question of how cooking itself alters the composition of the microbial ecosystems in our guts.” Yet it could be an important consideration, the authors suggested. “Heat alters the physicochemical properties of foods in ways that could impact the gut microbiome.”

For their study reported in Nature Microbiology—which results from a seven-year collaboration between Turnbaugh and Harvard evolutionary biologist Rachel Carmody, PhD—the researchers examined the impact of cooked vs raw diet on the microbiomes of mice. Animals were fed diets of raw meat, cooked meat, raw sweet potatoes, or cooked sweet potatoes. The researchers selected these foods because it has already been shown that cooking changes the nutrients and other bioactive compounds in both meat and tubers.

To the researchers’ surprise, whether the mice were fed raw or cooked meat had no discernible effect on their gut microbes. In contrast, diets containing raw vs cooked sweet potatoes significantly altered the composition of the animals’ microbiomes, as well as patterns of microbial gene activity and critical metabolites produced by the microbes. “Cooking impacted the gut microbiome differently on meat versus tuber diets,” the investigators noted. “The gut microbiomes of mice fed raw and cooked meat were similar in composition and transcriptional profile … By contrast, gut microbial community structure on the cooked tuber diet were fundamentally distinct.”

To confirm their findings the researchers then tested diets containing a more diverse array of cooked and raw vegetables. Carrying out what Turnbaugh referred to as a “mad scientist experiment,” they fed the mice an assortment of raw and cooked sweet potato, white potato, corn, peas, carrots, and beets, and again saw differences in gut microbiota. They linked the microbial changes they saw were down to two potential key factors. First, cooking can influence the uptake of starch in the small intestine and so reduce the amount reaching the colon, which is where the majority of microbial communities reside. Second, cooking could denature antimicrobial compounds that are either present naturally in raw food or which have been introduced through modern farming methods, and so limit their bioactivity and impact on gut bacterial species. “We were surprised to see that the differences were not only due to changing carbohydrate metabolism but also may be driven by the chemicals found in plants,” Turnbaugh said. “To me, this really highlights the importance of considering the other components of our diet and how they impact gut bacteria.”

The researchers also noticed that raw diets caused mice to lose weight. Wondering whether this weight loss was a result of changes to the animals’ microbiomes, the team transplanted the altered gut microbiomes into mice that were fed on a regular diet of mouse chow. However, rather than resulting in the animals losing weight, the microbiome transfer was associated with the otherwise normally fed animals putting on extra fat. The authors say they are still investigating this seemingly paradoxical finding.

In collaboration with colleagues at the U.S. Department of Energy’s Joint Genome Institute in Walnut Creek, Turnbaugh’s team then performed a detailed analysis of the chemical changes that cooking produced in each of the plants that they had fed to the mice. Their analyses resulted in a shortlist of compounds that might help to explain how these diets impacted the animals’ microbiomes, which the authors are further evaluating.

In a subsequent set of experiments to determine whether raw and cooked diets can similarly affect microbiome changes in humans, the researchers partnered with a professional chef—also a Harvard graduate student—who prepared experimentally comparable raw and cooked menus for a group of eight adult volunteers. The participants tried each diet for three days each in random order, then submitted stool samples for researchers to analyze their microbiomes. The results confirmed that the distinct diets did lead to significant gut microbiota alterations. “It was exciting to see that the impact of cooking we see in rodents is also relevant to humans, although interestingly, the specifics of how the microbiome was affected differed between the two species,” Turnbaugh said. “We’re very interested in doing larger and longer intervention and observational studies in humans to understand the impact of longer-term dietary changes.”

Understanding how diet impacts the microbiome has important implications for how our gut microbes influence weight gain and other aspects of human health, Turnbaugh commented. The study also raises questions about how human-associated microbes have evolved over thousands of years to adapt to our culinary culture, and whether this adaptation could have important implications for modern health. “Taken together, our results show that cooking plants rich in low digestibility starch, a routine part of daily life, can have profound impacts on the gut microbiome, consistent with recent in vitro data,” the authors concluded. “The observation that everyday foods disrupt gut bacterial physiology when consumed raw raises opportunities for mining the human diet for therapeutics and prompts a polypharmacological view of the interactions between the gut microbiome and dietary small molecules. Finally, these results emphasize that humans and our microbiomes were both affected by the adoption of habitual cooking, perhaps helping to explain accelerated gut microbial change in the human lineage and encouraging steps toward a microbiome-informed understanding of human evolution.”

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