Diet-derived peptides mediate the effects of dietary protein source on gastrointestinal health

Integrated Assessment of the Functional Activity of the Gut Environment and Metabolic Profiles in Rats Fed an Insect-Based (Tenebrio molitor) Diet

Edible insects are increasingly proposed as sustainable protein sources in animal nutrition, yet their effects on gut microbial function, intestinal safety, and systemic metabolism require comprehensive evaluation. This study investigated the impact of a diet containing 35% Tenebrio molitor meal on the functional activity of gut environment and host metabolic profiles in rats, in comparison with diets containing chicken hydrolysate or a standard laboratory diet. Female Wistar rats were fed the experimental diets for 60 days, after which fecal short-chain fatty acids (SCFAs), microbial enzyme activity, fecal water genotoxicity, and liver and spleen metabolomes were assessed. Rats fed the T. molitor diet exhibited significantly lower fecal concentrations of major SCFAs, including acetate, butyrate, valerate, and branched-chain fatty acids (BCFAs), indicating altered colonic fermentation. Both β-glucosidase and β-glucuronidase activities differed significantly between groups and were highest in the T. molitor group. β-Glucuronidase activity also decreased over time, whereas no significant group vs. time interaction was observed. Fecal water genotoxicity decreased markedly in the T. molitor group over time. Untargeted UHPLC–HRMS metabolomics revealed pronounced diet-dependent differences in metabolite profiles. In the liver, the insect-based diet was associated with the enrichment of glycerophospholipid metabolism, primary bile acid biosynthesis, and pyrimidine metabolism pathways, as well as lower abundance of metabolites assigned to riboflavin- and phenylalanine-related pathways. In the spleen, diet-associated differences involved metabolites assigned to lipid-related pathways, including glycerophospholipid, linoleic acid, and steroid-related metabolism, as well as nucleotide-associated pathways. These findings support further evaluation of complete insect-based formulations and highlight specific metabolic pathways that should be considered when evaluating the safety and physiological implications of insect-based feeds.

Gut microbiome-metabolome interactions during varied low-carbohydrate food consumption.

Low-carbohydrate (LC) foods have been associated with weight loss, insulin resistance, and reduced inflammation. Gut microbes may drive these effects by changing the host's immune and metabolic state, yet the optimal replacement strategies (e.g., protein vs. fat) and the biochemical impacts are still uncertain. Thus, we conducted a randomized cross-over study in canines (n = 35) using a high-carbohydrate food for 4 wk, followed by two 5-wk intervals of LC foods replacing carbohydrates with fat or protein. Feces and blood samples collected after each interval underwent metabolome profiling, as well as shotgun metagenomic and metatranscriptomic sequencing from feces. We observed strong associations between food and overall fecal and serum chemical and gut microbial composition. Bifidobacterium spp. were significantly reduced during consumption of either LC food, whereas many species from Firmicutes increased. In addition to broad taxonomic changes, we also found that several microbially associated metabolites (tryptophan derivatives, secondary bile acids, and short-chain fatty acid fermentation) shifted in abundance in response to differing LC foods. Broadly, we also identified a strong trend toward decreased amino acids in the feces of dogs fed LC foods, particularly the high fat food. Coupled with decreased fecal dipeptide levels and increased fecal ammonia, these findings indicate a broad metabolic shift within the gut microbiome, potentially toward protein catabolism. Together, the data suggest that diverse carbohydrate replacement strategies induce extensive gut reprogramming, with some changes dependent on whether carbohydrate energy was replaced with fat or protein.

Digestion-resistant proteins support the healthy metabolite profiles associated with plant-based diets.

Plant-based diets are associated with both positive health outcomes and a diverse gut microbiome. Such diets alter the microbiome's metabolic outputs, including increasing phenylalanine-derived phenols associated with beneficial health outcomes (hippuric acid and 3-phenylpropionate), while decreasing tyrosine-derived phenols considered uremic toxins (phenol sulfate and p-cresol sulfate). The mechanisms linking plant eating to these phenol metabolites are not known. Plant-based foods are fiber and phytochemical rich. They also contain proteins that are resistant to host digestion and thus reach the gut microbiome. Here, we show that fiber and digestion-resistant protein work in concert to shift the phenol profile by altering gut microbiome nutrient supply. Through isotope-tracing studies, we reveal that host secreted proteins are a source for phenol sulfate and p-cresol sulfate, while digestion-resistant dietary protein is the source for hippuric acid and 3-phenylpropionate. Fiber decreases bacterial digestion of host secreted proteins (e.g., mucins) and thus suppresses tyrosine-derived phenol sulfate and p-cresol sulfate, whose levels correlate with the mucin-digesting bacterial family Oscillospiraceae. Digestion-resistant dietary protein increases bacterial access to phenylalanine and thereby boosts phenylalanine-derived hippuric acid and 3-phenylpropionate. Thus, digestion-resistant plant protein modulates microbiome metabolism and, together with fiber, supports healthy metabolite profiles associated with plant-based diets.

Sucrose-free low-fat diet induces metabolic dysfunction through gut dysbiosis and colonic inflammation in mice

Low-fat diets are widely promoted as health-protective; however, the consequences of removing sucrose within a low-fat dietary framework remain unclear. Here, we investigated the effects of a sucrose-free low-fat diet (SF-LFD) compared with a sucrose-containing low-fat control diet (C-LFD) in mice (n=6/group) over 16 weeks. Despite unchanged body and liver weights, SF-LFD feeding resulted in impaired glucose tolerance, reduced insulin sensitivity, and broad alterations in circulating metabolic hormones, including elevated C-peptide, incretins, ghrelin, and resistin, as well as reduced fasting insulin. 16S rRNA sequencing revealed that SF-LFD markedly disrupted gut microbial diversity and composition, with depletion of short-chain fatty acid–producing commensals, including Lactobacillus murinus and members of the Lachnospiraceae family, and enrichment of taxa associated with inflammatory or stress-adapted states, including Helicobacter ganmani, Odoribacter splanchnicus, and Alistipes species. This dysbiosis was accompanied by pronounced colonic inflammation characterized by crypt architectural disruption, loss of goblet cells, submucosal expansion, increased CD3+ T-cell and F4/80+ macrophage infiltration, and robust upregulation of inflammatory mediators, including Il1b, Il6, Ccl2, Rorγt, and Tbx21. SF-LFD feeding induced hepatic microvesicular steatosis, lobular inflammation, recruitment of F4/80+ and CD11c+ immune cells and increased hepatic expression of IL1b and IL6. Together, these findings suggest that sucrose elimination from a low-fat diet disrupts gut microbiota, impairs metabolic homeostasis, and promotes gut and liver inflammation, revealing an unrecognized dietary trigger of metabolic dysfunction.

Effects of dietary fiber on the intestinal humoral immune response via interactions with the microbiota 2260105

The Western diet, rich in fats and low in fermentable fibers, has been associated with a range of immune-mediated inflammatory diseases. Dietary fiber is the main energy source for gut bacteria, promoting a rich microbial diversity. We have previously demonstrated that microbiota changes induced by a low-fermentable fiber diet (LFF) impair the development of several intestinal T cell populations. However, the importance of dietary fiber for the intestinal humoral immune system is less understood. Secretory IgA (sIgA) is essential for maintaining gut microbiota homeostasis. Here, we show that sIgA is significantly reduced in the small intestinal and fecal contents of mice fed a low fiber diet compared to mice fed a standard chow (SC). IgA secretion by PC is not impaired, as shown by ELISA of culture media from sorted IgA+ PC from SC and LFF-fed mice. However, flow cytometry and ELISpot assays revealed that low IgA levels are due to a reduction in numbers of small intestinal lamina propria IgA+ PC in LFF-fed mice, while other isotypes are not affected. Using T cell deficient mice, we demonstrate that LFF diet reduces T-dependent, but not T-independent, sIgA. Future studies will elucidate how changes in the microbiota and dietary fiber result in the loss of IgA+ PCs. To this end, time-stamping of PC will allow to track survival and turnover rate in LFF and control mice. These results provide insight into the interactions between fiber, the microbiota, and B cell responses, and further our understanding on how diet modulates the mucosal immune response. 5R01DK129950 Mucosal and Regional Immunology (MUC)

Effects of dietary γ-aminobutyric acid supplementation on growth, feed intake, and intestinal health of the juvenile Chinese mitten crab (Eriocheir sinensis) fed with high plant protein diets