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Anthamatten, L.

Publications and source records attributed to Anthamatten, L..

2 recordsLinked to original sources

Mapping gut bacteria into functional niches reveals the ecological structure of human gut microbiomes

Microbiomes are an essential contributor to the metabolic activity in the human gastrointestinal tract. The fermentation of otherwise indigestible nutritional components like dietary fibers relies on a complex interplay of metabolic pathways that are distributed across the individual bacteria. Yet, which of the bacteria are responsible for which parts of the distributed metabolism and how they should be grouped together is insufficiently understood. Here, we present the NicheMap, an approach to map the different bacterial taxa that make up the gut microbiome onto the different functional niches of microbial carbohydrate fermentation. Our approach uses in vitro measurements of bacterial growth and metabolic activity to identify which bacterial taxa are responsible for which metabolic function in the relevant complex context of whole human fecal microbiomes. We identified characteristic taxa selected for by a panel growth substrates representative of dietary components that are resistant to digestion by host enzymes. These characteristic taxa offer predictions of which bacteria are stimulated by the various components of human diet. We validated these predictions using microbiome data from a human nutritional supplementation study. We suggest a template of how bacterial taxonomic diversity is organized along the trophic cascade of intestinal carbohydrate fermentation. We anticipate that our results and our approach will provide a key contribution towards building a structure-function map for gut microbiomes. Having such a map on hand is an important step in moving the microbiome from a descriptive science to an interventional one.

microbiology↗

Co-cultivation is a powerful approach to produce a robust functionally designed synthetic consortium as a live biotherapeutic product (LBP)

The successes of fecal microbiota transplants (FMT) have provided the necessary proof-of-concept for microbiome therapeutics. Because of the many risks and uncertainties associated with feces-based therapies, defined microbial consortia that modify the microbiome in a targeted manner have emerged as a promising safer alternative to FMT. The development of such live biotherapeutic products has important challenges, including the selection of appropriate strains and the production of the consortia at scale. Here, we report on an ecology and biotechnology-based approach to microbial consortium design that overcomes these issues. We designed a nine-strain consortium that emulates the central metabolic pathways of carbohydrate fermentation in the healthy human gut microbiota. We show that continuous co-culturing the bacteria produce a stable consortium whose activity is distinct from an equivalent mix of individually cultured strains. Further, we showed that our function-based consortium is as effective as FMT in counteracting dysbiosis in a dextran sodium sulfate mouse model of acute colitis. We propose that combining a bottom-up functional design with continuous co-cultivation is a powerful strategy to produce robust, functionally designed synthetic consortia for therapeutic use.

microbiology↗