Gut Microbes
A new study from Washington University School of Medicine in St. Louis shows that beneficial gut microbes thrive when fed specific fiber types. The researchers developed artificial food particles that allow them to measure how different fiber types are processed by human gut bacteria as the fibers transit through the mouse intestine. The artificial food particles consist of magnetic beads with fiber molecules coating the surface. Different colored fluorescent labels allow the researchers to track which fiber type is attached to which bead. [Michael Patnode]

Scientists at Washington University School of Medicine in St. Louis have identified components of dietary fiber that encourage the growth and metabolic activity of gut microbes linked with good health. The results from studies in mice colonized with human microbiota, provide new insights into how gut microbial species compete and cooperate for fiber components, and could ultimately help scientists to develop micobiota-directed foods (MDFs) that will selectively increase the abundance of beneficial gut microbes.

“We are in the midst of a revolution in food science—where the naturally occurring molecules present in various food staples are being identified using advanced analytic tools,” said Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser distinguished university professor and director of the Edison Family Center for Genome Sciences & Systems Biology, who headed the research. “The resulting encyclopedias of food ingredients are providing an opportunity to understand how gut microbes are able to detect and transform these ingredients to products they use to satisfy their own needs, as well as share with us. Cracking the code of what dietary ingredients beneficial microbes covet is a key to designing foods that enhance health.” The Washington University School of Medicine team, working with colleagues in the United States, France, and Saudi Arabia, reported their studies in Cell, in a paper titled, “Interspecies Competition Impacts Targeted Manipulation of Human Gut Bacteria by Fiber-Derived Glycans.”

Increasing evidence indicates that the microbial communities in our guts impact on how our bodies function, and this has spurred work aimed at developing microbiota-directed approaches to improving health. A strategy based on MDFs is an “obvious choice,” the authors stated, “as diet has pronounced rapid effects on microbial community configuration.”

Eating plant polysaccharides as dietary fiber has been linked with multiple health benefits, but typical Western diets lack fruits, vegetables, whole grains, and legumes that are high in fiber. In fact, humans largely depend on gut microorganisms to digest fibers in the diet, the authors continued. And while fibers actually comprise diverse and complex molecular components, its not known which of these are used by gut bacteria to benefit health. As the authors noted, “Achieving a better understanding of the mechanisms by which human gut bacterial species interact with dietary polysaccharides, and with one another, should facilitate development of fiber-based interventions that establish, restore, and/or sustain health-promoting microbiota functions.”

“Fiber is understood to be beneficial,” Gordon commented. “But fiber is actually a very complicated mixture of many different components. Moreover, fibers from different plant sources that are processed in different ways during food manufacturing have different constituents. Unfortunately, we lack detailed knowledge of these differences and their biological significance. We do know that modern Western diets have low levels of fiber; this lack of fiber has been linked to loss of important members of the gut community and deleterious health effects.”

In an effort to understand which types of fiber promote different types of beneficial microbes in the human gut, and the nature of their active ingredients, the researchers screened 34 types of fiber provided by a food company. Some of these were purified from byproducts of food manufacturing, including fruit and vegetable peels that are thrown out during processed food production.

The researchers colonized germ-free mice with gut microbes that are found in a typical healthy human gut, and sequenced the microbial genomes to provide a catalog of their genes. Groups of mice containing model human gut microbiomes were then fed a Western-type high-fat, low-fiber diet, and were used to screen the effects of 144 diets containing different types and amounts of the fiber supplements on the microbial communities. The investigators monitored the effects of the added fibers on the abundance of the different types of microbes, as well as their protein expression. “Microbes are master teachers,” Gordon said. “The microbial genes that respond to the different fibers provided an important clue as to what kinds of molecules in a given type of fiber a given community member preferred to consume.”

This graphical abstract depicts an in vivo approach which explains the mechanism by which gut microbes metabolize dietary fibers and paves a path towards the development of microbiota-directed foods that provide metabolic benefits to the host. [Patnode et al./Cell]

The experimental approach allowed the investigators to carry out a comprehensive, high-resolution proteomics study of all changes to bacterial proteins in response to the different fiber types. Combining the results with genetic screens the investigators were able to identify particular fiber sources, their bioactive molecular components, and the bacterial genes that increased when diets were supplemented with different fibers. They focused on analyzing genes in Bacteroides species, because members of this bacterial group contain dietary fiber-metabolizing genes that are not present in the human genome.

“Our screen identified food-grade fibers that selectively affected different species belonging to a group of bacteria known as Bacteroides, explained first study author, Michael L. Patnode, PhD, a postdoctoral researcher in Gordon’s lab. “Our experiments showed that in pea fiber, the active molecular constituents included a type of polysaccharide called arabinan, whereas in citrus pectin recovered from orange peels, another type of polysaccharide called homogalacturonan was responsible for expansion of the bacteria.”

The results indicated that some Bacteroides species in a microbial community directly compete with each other to consume components of dietary fibers, while others defer to their neighbors. Understanding these relationships is important for developing foods that are optimally processed by different microbial populations that live together in the gut, according to the researchers.

The next stage was to dissect the identified relationships further. The researchers developed fluorescently labeled artificial food particles composed of different types of magnetic microscopic glass beads, to which they bound different types of carbohydrates from the different fibers. The nutrient-containing particles were then fed to mice colonized with microbial communities containing defined combinations of Bacteroides species. The food particles were recovered after passing through the animals’ intestines, and the amount of polysaccharide remaining on the particles’ surfaces was measured.

“These artificial food particles acted as biosensors, allowing us to decipher how inclusion or omission of Bacteroides influenced the community’s ability to process the different polysaccharides present on the different beads,” Patnode said. “We were excited to see how these ‘biosensors’ could be used to assess the processing of particular fiber components by particular bacterial species.”

By feeding these particles to mice that either carried or did not carry a dominant fiber-consuming species, the authors found that subordinate species effectively waited in line to step up and consume the fiber. “We had suspected there might be competition going on among the different strains and that some would be stronger competitors than others,” Patnode added. Proteomics analyses and genetic screens confirmed that there was a hierarchy of fiber consumption among the species present in these model bacterial communities.

“Here, we identify dietary fibers and constituent bioactive components that increase the fitness of targeted Bacteroides (B. thetaiotaomicron, B. vulgatus, B. caccae, and/or B. cellulosilyticus) in vivo …” the authors concluded. “Our approach identified bioactive components in compositionally complex fibers that impact specific members of the microbiota. Obtaining this type of information could inform efforts to enrich for these active components through judicious selection of cultivars of a given food staple, food processing methods, or existing waste streams from food manufacturing.”

Gordon noted that as well as being used as biosensors to define the functional capabilities of a person’s microbial community, the nutrient-containing artificial food particles could also help food scientists develop methods for producing more nutritious foods containing different combinations of health-promoting bioactive fiber components. “It’s important to understand how the presence of a particular organism affects the dining behavior of other organisms—in this case, with regard to different fibers,” he concluded. “If we are going to develop microbiota-directed foods aimed at providing benefits to human health, it’s important to find ways to determine which food staples will be the best source of nutrients and how the microbiota will respond.”

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