From mouse to man: translating findings in mouse study into a human cohort (Luxembourgish Fiber Cohort: Lux-FiCo)

In many nations with a Western-style diet, the average consumption of dietary fiber is roughly half of the recommended daily intake of 25 or 38 g/day for women or men respectively. The decline in fiber consumption parallels an increase in prevelance of diseases such as colorectal cancer, multiple sclerosis, and cardiometabolic diseases. This explanation for this association could rest in the trillions of commensal microorganisms that inhabit the gut and carry out functions that support human health. For example, fiber-degrading bacteria convert host-indigestible dietary fibers into short chain fatty acids, which provide energy for colonic cells, support mucus production, and modulate the immune system. Previously, we have used a mouse model with a defined human gut microbiota to show that removal of fiber from the diet favors proliferation of bacteria that degrade the gut's protective mucin lining (Desai et al., 2016, Cell). We seek to translate these findings to humans using a 2x2 crossover study among healthy adults. Forty participants will be randomly assigned to a low- or high- fiber dietary intervention and then, following a washout period to reverse any changes, switched to the other diet type. We will also administer questionnaires, obtain basic anthropomorphic measures, and collect biological samples (blood, urine, and stool). When fed a low-fiber diet, participants are expected to exhibit and increased abundance of mucin-degrading bacteria in their stool and increase in mucolytic enzymes. We will identify bacteria by sequencing the V4 region of the 16S rRNA gene and will further characterize their functional properties using culture-based methods and enzymatic assays. We will measure inflammatory markers using CyTOF to assess whether these diets exert detectable changes in host immune function. Finally, we will see whether the observed changes can be linked to host genetics. The data generated will be used to improve understanding of the impact of a Western-style, low fiber diet on the structure and function of gut microbial communities.