Non-SCFA microbial metabolites associated with fiber fermentation and host health

Grant, Erica T.; De Franco, Hélène; Desai, Mahesh S.

doi:10.1016/j.tem.2024.06.009

Cited by 2 publications

(1 citation statement)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may align with prior human studies reporting that epilepsy is associated with deficient levels of SCFA-producing bacteria, which are further reduced by KD therapy to promote seizure control 16,22,48 . Beyond SCFAs, several other carboxylic acid metabolites, neurotransmitters, vitamins, and bile acids are also modulated by fiber fermentation 49,50 . This suggests that the fiber effects on seizure resistance may not be mediated by common SCFAs , but rather by other non-SCFA metabolites generated by fiber fermentation or indirect effects of fiber fermentation on the microbiome and host.…”

Section: Discussionmentioning

confidence: 99%

Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice

Özcan,

Yu,

Dinh

et al. 2024

Preprint

View full text Add to dashboard Cite

The gut microbiome is emerging as an important modulator of the anti-seizure effects of the classic ketogenic diet. However, many variations of the ketogenic diet are used clinically to treat refractory epilepsy, and how different dietary formulations differentially modify the gut microbiome in ways that impact seizure outcome is poorly understood. We find that clinically prescribed ketogenic infant formulas vary in macronutrient ratio, fat source, and fiber content and also in their ability to promote resistance to 6-Hz psychomotor seizures in mice. By screening specific dietary variables for their effects on a model human infant microbial community, we observe that dietary fiber, rather than fat ratio or source, drives substantial metagenomic shifts. Addition of dietary fiber to a fiber-deficient ketogenic formula restores seizure resistance, and supplementing protective ketogenic formulas with excess dietary fiber further potentiates seizure resistance. By screening 13 fiber sources and types, we identify distinct subsets of metagenomic responses in the model human infant microbial community that correspond with increased seizure resistance in mice. In particular, supplementation with seizure-protective fibers enriches microbial representation of genes related to queuosine biosynthesis and preQ0biosynthesis and decreases representation of microbial genes related to sucrose degradation, which is also seen in seizure-protected mice that are fed fiber-containing ketogenic infant formulas. Overall, this study reveals that different formulations of clinical ketogenic diets, and dietary fiber content in particular, differentially impact seizure outcome in mice, likely through modification of the gut microbiome. Understanding interactions between dietary components of the ketogenic diet, the gut microbiome, and host susceptibility to seizures could inform novel microbiome-guided approaches to treat refractory epilepsy.

show abstract

Section: Discussionmentioning

confidence: 99%

Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice

Özcan,

Yu,

Dinh

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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

Grant,

Parrish,

Boudaud

et al. 2024

Microbiome

View full text Add to dashboard Cite

Background 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. Results Broad-scale metabolomics analysis of cecal contents revealed that fiber deprivation consistently reduced the concentrations of microbiota-produced B vitamins. This phenomenon was not always explained by reduced biosynthesis, rather, metatranscriptomic analyses pointed toward increased microbial usage of certain B vitamins under fiber-free conditions, ultimately resulting in a net reduction of host-available B vitamins. Broad immunophenotyping indicated 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 microbially produced B vitamins and restored immune homeostasis. Conclusions Our findings highlight the potential to use defined fiber polysaccharides to boost microbiota-derived B vitamin availability in an animal model and to regulate local innate and adaptive immune populations of the host.

show abstract

Non-SCFA microbial metabolites associated with fiber fermentation and host health

Cited by 2 publications

References 82 publications

Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice

Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice

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

Contact Info

Product

Resources

About