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Microbiome-modifying foods with specific combinations of plant fibers
Researchers at Washington University School of Medicine in St. Louis have identified prototype snack ingredients that have been formulated to consciously alter the gut microbiome in ways that can be linked to health. The scientists translate results from animal models and have shown in two pilot studies on humans with overweight participants that snacks containing combinations of specially selected fiber types influence elements of the microbiome that are involved in the metabolism of fiber components. This shift in the microbiome has been linked to changes in groups of blood proteins that are biomarkers and regulators of many facets of physiology and metabolism. These blood proteins have shifted in ways that could improve long-term health.
The study will be published on June 24 in the journal Nature.
“Poor nutrition is an urgent and complex problem worldwide that is driven by many factors, including an oversupply of high-fat and low-fiber foods in typical Western diets,” said the study’s lead author, Jeffrey I. Gordon, MD, who is Dr. Robert J. Glaser Distinguished University Professor and Director of the Edison Family Center for Genome Sciences & Systems Biology at Washington University School of Medicine. “As snacks are a popular part of the Western diet, we are working to develop a new generation of snack formulations that people enjoy eating and that support a healthy gut microbiome that affects many aspects of well-being.”
The human gut is home to a microbiome made up of tens of trillions of microbes that contain millions of different genes that perform functions not provided by the roughly 20,000 protein-coding genes in the human genome. According to the researchers, the nutritional value of food is determined in part by the products of the food’s unique metabolism through the gut microbiome. Gordon and his colleagues focus on characterizing which food components interact with which components of the gut microbiome and how this interaction shapes various features of human biology. The aim is to usher in a new era in nutritional science that will produce affordable, more nutritious foods from sustainable sources that can be used to treat or prevent various forms of malnutrition – be it malnutrition or obesity in children or adults.
The high-fat, low-fiber diet consumed in the US and other western countries does not support a diverse and healthy gut microbiome. In addition, a high-fiber diet is linked to a lower risk of chronic conditions such as cardiovascular disease, type 2 diabetes, and obesity. However, fiber consists of complex and diverse mixtures of biomolecules, many of which the human body cannot break down on its own. The nature of these blends depends on the source of the fiber and how it is processed when incorporated into food. Previous work by Gordon’s team identified specific plant fibers that were affordable and available in large quantities from sustainable sources – such as from peel, bark, and peels that would otherwise be thrown away – that enhanced the performance of certain beneficial gut microbes that are underrepresented in many overweight people Adults on Western diets.
In this new report, the researchers analyzed data from subjects who participated in two studies who were overweight or obese who were given meals that mimicked a typical Western diet. These diets were complemented by one of three fiber-containing snack prototypes. One contained fiber made only from peas. Another contained a combination of pea fiber and inulin (a fiber found in a number of fruits and vegetables, including wheat, onions, bananas, asparagus, artichokes, and chicory root). A third snack contained pea fiber and inulin, as well as fiber from the pulp of orange and barley bran. The snacks were developed in collaboration with Mondelēz International, a global snack food company.
In the first study, participants ate the high-fat, low-fiber meals for 10 days before adding a pea-fiber snack to their diet for two weeks, followed by two weeks in which participants continued the high-fat, low-fiber diet without the fiber snack . A similar design was used in the second study, but supplementation was with the snack, which contained both pea fiber and inulin, and after a washout period, the snack contained four components of fiber: pea, inulin, orange, and barley bran.
The researchers analyzed the patients’ gut microbiome during different phases of the study, as well as the levels of more than 1,300 proteins in their blood. Gordon and his colleagues found that many of the components of the microbiome that responded to and processed the various snack fiber prototypes in the study participants were the same as those found in their previous experiments with gnotobiotic mice colonized with human gut microbes. responded to the same fibers. Gnotobiotic mice are born and raised in sterile conditions so the nature of the gut microbes can be tightly controlled for scientific studies. In addition, they found that combining four different fibers, the snack had a broader effect on microbiome genes, which encode the metabolic machinery needed to extract nutrients from the fibers, when compared to the single-fiber or two-fiber snacks . These results confirmed the use of their preclinical models as a way to expedite the screening and selection of fibers for incorporation into food prototypes.
Researchers developed data mining approaches that enabled them to identify statistically significant changes in certain groups of microbiome genes and relate them to changes in the concentrations of groups of blood proteins involved in a remarkably wide range of physiological processes that range from energy metabolism – including glucose metabolism – to immune responses, blood clotting and blood vessel function, as well as to the biology of bones and nerve cells.
“We were encouraged to see the effects of these fiber snacks on the gut microbiome and human physiology itself in these relatively brief studies,” said lead author Omar Delannoy-Bruno, PhD, member of the interdisciplinary team that carried out this work.
Co-author Michael J. Barratt, PhD, associate professor of pathology and immunology and executive director of the Center for Gut Microbiome and Nutrition Research at Washington University, said, “These pilot studies were not designed to test whether the fiber snacks were can produce significant long-term changes in body weight or frequently measured biomarkers of cardiometabolic health. Therefore, the benefits of these interventions need to be explored in larger, longer clinical trials. In addition, these small studies were conducted under strictly controlled diet conditions. An important next step will be to study the effects of the fiber snacks on participants who can eat as usual. “
Gordon added, “With a better understanding of the effects of different types of fiber on components of the microbiome, we hope we can deliver a snack that people want to eat while also contributing to healthier diets, especially for those who might otherwise may have limited access to nutritious foods. “
This work was funded by grants from the National Institutes of Health (NIH) grants number DK078669, DK70977, and UL1-TR002345, and Mondelēz International. Controlled nutrition studies in human subjects were overseen by members of the Clinical Science Research Core of the Nutrition Obesity Research Center (NORC), supported by NIH grant P30 DK056341. Plasma proteome datasets were generated by the Washington University School of Medicine Genome Technology Access Center, which is supported in part by NIH Grants P30 CA91842 and UL1TR002345. Additional assistance has been provided through NIH Grants R25GM103757, T32GM007067, and T32HL130357. Gordon received a Thought Leader Award from Agilent Technologies.
Gordon is a co-founder of Matatu Inc., a company that characterizes the role of diet and microbiota interactions in animal health. Other authors report that they are co-founders of Phenobiome Inc., a company engaged in the development of computational tools for predictive phenotype profiling of microbial communities, as well as Evolve Biosystems, interVenn Bio, and BCD Bioscience – companies involved in the characterization of glycans and the development of carbohydrate applications for human health. Three co-authors are members of Mondelēz International.
A patent application relating to the fiber snack formulations described in this report has been filed and published (WO 2021/016129).
Delannoy-Bruno O, et al. Evaluation of microbiome-directed fiber snacks in gnotobiotic mice and humans. Nature. 06/24/2021.
The 1,500 faculty physicians at Washington University School of Medicine are also the medical staff for the Barnes-Jewish and St. Louis Children’s Hospitals. The School of Medicine is a leader in medical research, teaching, and patient care and consistently ranks among the best medical schools in the country according to the US News & World Report. The School of Medicine is affiliated with BJC HealthCare through its affiliation with Barnes-Jewish and St. Louis Children’s Hospital.