Dietary fibers boost gut microbiota-produced B vitamin pool and alter host immune landscape

Abstract

Dietary fibers can alter microbial metabolic output in support of healthy immune function, however, the impact of distinct fiber sources and immunomodulatory effects beyond short-chain fatty acid production are underexplored. In an effort to discern the effects of diverse fibers on host immunity, we employed five distinct rodent diets with varying fiber content and source in specific-pathogen-free, gnotobiotic (containing a 14-member synthetic human gut microbiota), and germ-free mice. Broad-scale metabolomic analysis of cecal contents showed a reduction in microbiota-produced B vitamins during fiber deprivation. Fiber deprivation shifted the ratio of transcripts corresponding to bacterial enzymes involved in B vitamin synthesis versus downstream utilization, resulting in a net reduction of host-available B vitamins. Broad immunophenotyping identified that the local gut effector immune populations and activated T cells accumulate in a microbiota-dependent manner. Supplementation with the prebiotic inulin recovered the availability of microbial-produced B vitamin and restored immune homeostasis. Our findings highlight the biotechnological potential of defined fiber polysaccharides to boost microbiota-derived B vitamin availability to the host and regulate local innate and adaptive immune populations, which may have critical implications for immune homeostasis in a variety of diseases.

Maternal diet and gut microbiome composition modulate early‐life immune development

“…To this point, Lubin et al demonstrated that restricting the microbiome to a pre‐weaning community halts immune development and increases susceptibility to Salmonella infection (Lubin et al , 2023), reflecting the need for a functionally balanced synthetic community to elicit normal immune development. As with other gnotobiotic models, the 14SM immune profiles typically represent an intermediate between GF and SPF colonization states in adulthood, potentially due to low diversity, low bacterial density and/or absence of specific immunogenic bacteria such as segmented fillamentous bacteria (Parrish et al , 2022b). Addition of new members may be a promising approach to refine these models, although it remains difficult to completely recapitulate SPF immune profiles (Afrizal et al , 2022).…”

“…All parental mice were maintained on the FR diet, which is a standard rodent chow (SAFE ® R04, Augy, France), until 2 weeks after the oral gavage. After this period, the parental mice designated as FF were switched to the custom FF chow, which is a modified version of Harlan TD.08810 diet and is manufactured by the same vendor as the FR diet, as previously reported (Parrish et al , 2022b). Mice were maintained on the FF diet for at least 20 days prior to setting breeding pairs and the respective diets were administered ad libitum for the remainder of the study.…”

Maternal diet and gut microbiome composition modulate early life immune development

“…Detailed compositions of the fiber-rich (FR) and fiber-free (FF) diets used in this study are as previously reported (Parrish et al , 2022c). Gnotobiotic FR mice were fed a standard rodent chow (SAFE®R04, Augy, France).…”

“…Gnotobiotic FR mice were fed a standard rodent chow (SAFE®R04, Augy, France). The FF diet is a modified version of Harlan TD.08810 diet, manufactured by the same vendor as the standard chow, as previously reported(Parrish et al , 2022b).…”

Diet-driven differential response ofAkkermansia muciniphilamodulates pathogen susceptibility

“…Bacterial DNA was extracted from fecal pellets by phenol-chloroform extraction, as previously described (Steimle et al , 2021). Total RNA was extracted from the host mesenteric lymph nodes, colonic tissue, or cecal contents at 3 DPI, as previously described (Grant et al , 2023; Parrish et al , 2022). RNA integrity was determined using an Agilent 2100 Bioanalyzer system and the RNA was stored at –80°C until further analysis.…”