Oral Multienzyme Supplementation Alters Postprandial Plasma Nutrient Concentrations after a Mixed Meal in Healthy Middle-Aged and Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Journal of Nutrition · 2026-02-07

BACKGROUND: Age-related decline in digestive function increases malnutrition risk. Supplementing meals with digestive enzymes may improve macronutrient digestion and bioavailability in adults reaching older ages. OBJECTIVES: To assess postprandial plasma nutrient concentrations after co-ingestion of a mixed meal and a mixture of 6 enzyme preparations (ENZ), including proteases, lipase, amylase, and glucoamylase. METHODS: Thirty middle-aged and older adults (56 ± 11 y; 18 females, 12 males) ingested chicken, peas, potatoes, and butter (435 kcal; 34 g protein, 51 g carbohydrate, 11 g fat) with either ENZ or placebo (PLA) in a randomized crossover fashion. Blood samples were collected at baseline and throughout a 0-5 h postprandial period for measurement of plasma amino acid, insulin, glucose, and nonesterified fatty acid (NEFA) concentrations. Clustering of postprandial amino acid responses was conducted in MFuzz, and logistic regression for response groups was conducted in JMP 18.2.0 (JMP Statistical Discovery LLC). RESULTS: Plasma amino acid concentrations were not statistically different between treatments (PLA compared with ENZ) over the postprandial period (all P > 0.05). Leucine time to maximum concentration was significantly faster (P = 0.047) with ENZ (121.2 ± 55.9 min) compared with PLA (141.0 ± 49.2 min). Postprandial plasma glucose concentrations (P = 0.04) and total NEFA (P = 0.001) were higher with ENZ compared with PLA. Three distinct response patterns (clusters) were detected within and across all postprandial amino acid categories. Differences in habitual macronutrient intake and interactions between sex, lean mass, and BMI distinguished participants with an earlier time to maximum postprandial leucine concentration when consuming ENZ compared with PLA from those with stable responses. CONCLUSIONS: Multienzyme supplementation improved macronutrient digestion of a mixed meal in middle-aged and older adults. For plasma amino acids, this benefit was most pronounced in adults with lower BMI and higher lean mass, and the effect was sex-dependent. This study was registered at clinicaltrials.gov as NCT05211440.

Age-related Changes in Intestinal Sphingolipid Metabolism and Microbiota-dependent Lipid Absorption

Physiology · 2025-05-01 · 1 citations

Aging is a degenerative process linked to increased inflammation and dysfunction of the intestinal epithelial barrier, which may impact nutrient absorption in the rapidly growing elderly population. Emerging evidence suggests that disruptions in intestinal host-microbiota crosstalk sphingolipids (SLs) may precede the decline in immune function and intestinal nutrient absorption observed with aging, but the mechanisms associated with this disruption remain poorly defined. Given the pivotal role of intestinal SL in regulating lipid metabolism and inflammation, we propose that age-related inflammation and reduced barrier integrity are linked to alterations in host-microbiota SL metabolism. Here, we utilized Liquid Chromatography/Mass Spectrometry (LC/MS)-based lipidomics to identify colonic digesta lipid alterations with aging in C57BL/6 mice (young= 3-4 m.o. vs. aged= 18-20 m.o.). First, we revealed that gut SL metabolism is robustly altered with age, hallmarked by the accumulation of numerous SLs and ceramides (Cer). Next, we investigated small intestinal expression of fatty acid (FA) synthesis and trafficking genes ( Fasn, Acc2, Elovl6, Cd36 , ApoB ) but did not observe significant differences. However, among SL metabolism genes ( Sptlc1, 2, Cers2 ,4, 6, Kdsr , Degs1,2 ), Cers6 was significantly higher ( p <0.01) in small intestine of young mice, which may indicate a greater synthesis of barrier ceramides that declines with age. Further, higher accumulation of SLs in digesta are strongly associated with signs of immune cell infiltration like calprotectin ( p <0.0001) and ex vivo immune toll-like receptor TLR4 reactivity of intestinal mucosa ( p <0.05) and feces ( p <0.001). Given that aging is associated with reduced intestinal resilience, we examined the effect of broad-spectrum antibiotic cocktail (ABX) challenge in young and aged mice. Following a one-week of ABX, mice were allowed to recover for 1 week washout period. Expression of FA and SL metabolism genes in the ileum was unaltered by ABX treatment after washout. Despite this, ABX exposure led to a robust accumulation of digesta triglycerides (TG) in aged mice after washout, indicating a heightened lipid malabsorptive phenotype with aging. Moreover, ABX-induced TG accumulation in the colon of aged mice is associated with an inability to recover their microbiome structure and persistent TLR4 immunogenicity of the digesta. Our findings are in line with a previous aged germ-free (GF) mouse (vs. specific pathogen-free mice; SPF) lipidomic analysis by Tsugawa, et al. ( Nature Aging, 2024), which shows greater SL accumulation in small intestine tissue during aging, with non-glycosylated SLs dominating in SPF mice and glycosylated SLs in GF mice, highlighting the role of gut microbiota in intestinal lipid homeostasis. Altogether, we show that aging and ABX disrupt intestinal lipids which may underlie the chronic inflammatory milieu and reduced barrier integrity. Future studies are needed to understand how aging disrupts intestinal host-microbiota lipid metabolism and nutrient absorption. Funding was provided by Vision 20/20 at the University of Illinois Urbana-Champaign This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

155 Personalized nutrition from pets to humans.

Journal of Animal Science · 2025-10-01

Abstract Introduction: Gut microbiota have far-reaching influence on animal physiology and health, but high inter-individual variation in microbial composition presents challenges in harnessing their full metabolic potential to improve health outcomes. Understanding how the gut microbiota responds to dietary modifications across species offers valuable insight into host-microbiota interactions and microbial community dynamics, ultimately guiding strategies to optimize microbial synthesis of health-promoting and health-deteriorating metabolites. This talk explores comparative microbial structural and functional changes of dogs vs cats to various dietary fiber sources, identifies shared and unique microbial taxa involved in health-related metabolite production, and discusses the potential for applying insights from the field of human personalized nutrition to tailored companion animal diets. Methods: In a series of crossover trials, dogs and cats were fed species-appropriate diets formulated with ten distinct fiber sources, each for a two-week period. Fecal microbiome composition via 16S rRNA gene amplicon sequencing and metabolite profiles via gas chromatography were analyzed at the conclusion of each dietary intervention. Microbiome data processing and analyses were conducted with the QIIME2 software platform. Results: Marked differences were observed in microbiome composition between species. Interestingly, diversity metrics and microbial metabolic responses, such as short-chain fatty acid concentrations, were divergent across fiber sources within and between species. Differential abundance modeling identified shared and unique microbial taxa related to fecal metabolite concentrations, offering potential targets for interventions aimed at modulating gut microbiota for companion animal health. Conclusions: These results emphasize the importance of considering species-specific gut microbiome responses to dietary fibers when formulating companion animal diets. The identification of key microbial taxa associated with health-promoting metabolites offers exciting opportunities to develop more tailored, individualized dietary strategies for improving companion animal health. Future studies will test probiotic, prebiotic, and synbiotic interventions targeting the microbes and metabolic pathways identified in these studies utilizing a personalized nutrition approach.

Comparing and optimizing protein extraction methods with different lysis buffers for the analyses of human fecal microbiome via metaproteomics approach

Journal of Microbiological Methods · 2025-08-29

Metaproteomic analysis offers critical insights into gut microbiome function; however, efficient microbial protein extraction from fecal samples remains challenging due to the complexity of different types of bacterial cell walls in the microbiome. In this study, we systematically compared three representative detergent-based lysis buffers (sodium dodecyl sulfate_urea, dodecyl β-D-maltoside_urea, sodium dodecyl sulfate_ dodecyl β-D-maltoside_urea) for metaproteomics sample preparation. After multiple levels of analyses, we identified SDS_DDM_urea as the most efficient option for extracting diverse microbial proteins, peptides, and identifying microbial species. Applying this optimized method to samples from a community based dietary intervention study (Summer Harvest Adventure), we found minimal group-level microbial diversity shifts during this type of intervention, but substantial individual-specific variations reflected by metaproteomics results. Functional analyses also revealed microbial protein changes, especially proteins related to metabolic adaptations, including enhanced carbohydrate metabolism, amino acid biosynthesis, vitamin transport, and increased expression of membrane-associated proteins. Our results highlighted the personalized microbiome response to dietary interventions and underscored the importance of selecting appropriate protein extraction methods to accurately capture microbiome functional dynamics in microbiome analyses via metaproteomics.

Gut microbiota dysbiosis in a novel mouse model of colitis potentially increases the risk of colorectal cancer

American Journal of Physiology-Gastrointestinal and Liver Physiology · 2025-05-05 · 5 citations

Ablation of hnRNPI in intestinal epithelia modulates gut microbiota; causing dysbiosis. Increased ratio of fecal Paraclostridium bifermentans to Dubosiella sp. is a signature of inflammation in hnRNPI knockout mice. hnRNPI knockout exacerbated colitis from dextran sodium sulfate challenge in knockout mice. Bacterial metabolites produced by P. bifermentans and Dubosiella newyorkensis could impact colon health in mice. hnRNPI gene ablation exacerbates chemically induced inflammation and colitis; potentially increasing cancer risk.

Social stress worsens colitis through β-adrenergic–driven oxidative stress in intestinal mucosal compartments

Brain Behavior and Immunity · 2025-12-17 · 1 citations

Psychological stress is a known risk factor for inflammatory bowel disease (IBD), but the mechanisms linking stress to worsened disease remain unclear. Because distinct stress paradigms activate different neuroimmune circuits, it is critical to investigate model-specific effects. We examined how social stress primes the gut for heightened inflammation and whether this is mediated by specific neuroendocrine pathways, including α2-/β-adrenergic (sympathetic) or glucocorticoid/ corticotropin-releasing hormone receptor (CRHR1) (HPA axis) signaling. Mice were exposed to social disruption (SDR) stress and pre-treated with pharmacological antagonists targeting α2-adrenergic receptors (idazoxan), β-adrenergic receptor (β-AR) (propranolol), glucocorticoid receptor (mifepristone), or CRHR1 (antalarmin). Intestinal epithelial cell (IEC) gene expression and microbiota composition were assessed following SDR. To determine disease impact, SDR was combined with either Citrobacter rodentium infection or dextran sulfate sodium (DSS)-induced colitis, with interventions including the β-AR inhibitors and the NADPH oxidase inhibitor apocynin. SDR significantly upregulated expression of Dual oxidase 2 (Duox2), Dual oxidase maturation factor 2 (Duoxa2), and inducible nitric oxide synthase 2 (Nos2) in IECs (2- to 8-fold, p < 0.0001), effects reversed by β-AR blockade but not α2-adrenergic, CRH, or glucocorticoid inhibition. SDR also induced microbial dysbiosis, characterized by reduced α -diversity and compositional shifts, which was rescued by propranolol. Stress exacerbated disease severity in both infectious (C. rodentium) and chemically induced (DSS) colitis, amplifying colonic expression of Duox2, Nos2, and Ccl2, especially. Apocynin mitigated stress-induced ROS/RNS production and body weight loss even prior to colitis onset, reduced colonic expression of key oxidative enzymes, especially DUOX2, and alleviated both chemically and infectious colitis severity. These findings provide strong evidence that social stress sensitizes the gut to inflammation through β-adrenergic and NADPH oxidase-driven oxidative stress, highlighting potential therapeutic targets for mitigating stress-exacerbated IBD.

Communities, mysteries, and pathophysiologies – Are gut microbes key to a healthy mind?

Brain Behavior and Immunity · 2025-01-21

Prebiotic fructan chain length influences enteric microbiota-host GABAergic signaling and intestinal motility

The Journal of Nutritional Biochemistry · 2025-12-20

Dietary fiber ingestion serves as a critical regulator of intestinal motility and the structure and function of the enteric microbiome. Yet, the extent to which subtle structural differences among fibers modulate motility via microbiota-host interactions remains undefined. GABA is a microbial metabolite intimately related to microbial fructan fermentation and host intestinal motility. The purpose of this study was to investigate how fructan chain length influenced microbiota-host signaling underlying ileal and colonic contractions. Male and female mice were pair-fed diets containing no fiber (fiber-free diet, FFD) or the same diet containing cellulose (CELL, fiber control), short-chain fructooligosaccharides (scFOS), or inulin (INU) for 2 weeks. scFOS and INU similarly enhanced total microbial load (fluorescence in situ hybridization), relative abundances of GABA-synthesizing bacteria (16S rRNA sequencing), and luminal GABA concentrations (ELISA) in the ileum and colon versus FFD. Conversely, scFOS altered expression (Fluidigm qPCR) of more motility- and GABA-related genes than INU in the ileum, whereas INU altered expression of more motility and GABA-related genes than scFOS in the colon. Incubation of ileal segments with GABA potentiated contraction force in INU but not scFOS ex vivo. Conversely, incubation of colon segments with GABA repressed contraction force in scFOS, reducing them to levels observed in INU with or without GABA. Notably, GABA altered contraction forces only in female mice. Our study highlights dietary fructan chain length as a determinant of segment- and sex-specific GABA-mediated intestinal motility and creates a rationale and framework for investigation of how prebiotic fiber structures influence microbiota-host interactions and physiology.

Social stress worsens colitis through β-adrenergic–driven oxidative stress in intestinal mucosal compartments

bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-18 · 1 citations

Abstract Psychological stress is a known risk factor for inflammatory bowel disease (IBD), but the mechanisms linking stress to worsened disease remain unclear. Because distinct stress paradigms activate different neuroimmune circuits, it is critical to investigate model-specific effects. We examined how social stress primes the gut for heightened inflammation and whether this is mediated by specific neuroendocrine pathways, including α2-/β-adrenergic (sympathetic) or glucocorticoid/ corticotropin-releasing hormone receptor (CRHR1) (HPA axis) signaling. Mice were exposed to social disruption (SDR) stress and pre- treated with pharmacological antagonists targeting α2-adrenergic receptors (idazoxan), β-adrenergic receptor (β-AR) (propranolol), glucocorticoid receptor (mifepristone), or CRHR1 (antalarmin). Intestinal epithelial cell (IEC) gene expression and microbiota composition were assessed following SDR. To determine disease impact, SDR was combined with either Citrobacter rodentium infection or dextran sulfate sodium (DSS)-induced colitis, with interventions including the β-AR inhibitor propranolol and the NADPH oxidase inhibitor apocynin. SDR significantly upregulated expression of Dual oxidase 2 (Duox2) , Dual oxidase maturation factor 2 (Duoxa2) , and inducible nitric oxide synthase 2 (Nos2) in IECs (2- to 8- fold, p &lt; 0.0001), effects reversed by β-AR blockade but not α2-adrenergic, CRH, or glucocorticoid inhibition. SDR also induced microbial dysbiosis, characterized by reduced alpha-diversity and compositional shifts, which was rescued by propranolol. Stress exacerbated disease severity in both infectious ( C. rodentium ) and chemically induced (DSS) colitis, amplifying colonic expression of Duox2 , Nos2 , and Ccl2, especially. Apocynin mitigated stress-induced ROS/RNS production and body weight loss even prior to colitis onset, reduced colonic gene expression of key oxidative enzymes, and alleviated both chemically and infectious colitis severity. These findings provide strong evidence that social stress sensitizes the gut to inflammation through β-adrenergic and NADPH oxidase–driven oxidative stress, highlighting potential therapeutic targets for mitigating stress-exacerbated IBD. Highlights Social disruption (SDR) and restraint stress (RST) activate distinct neuroendocrine pathways, with SDR driving epithelial ROS/RNS pathways via β-adrenergic signaling. β-adrenergic blockade prevents SDR-induced epithelial priming, microbial dysbiosis, and colitis exacerbation. NADPH oxidase inhibition with apocynin mitigates stress-induced oxidative stress and disease severity across different colitis models. Findings identify β-adrenergic and redox pathways as therapeutic targets for stress-exacerbated IBD.

Nutrition Interventions in the Treatment of Gastrointestinal Symptoms during Cancer Therapy: A Systematic Review and Meta-analysis

Advances in Nutrition · 2025-07-22 · 8 citations

Modern cancer therapy is effective at reducing tumor burden and extending lifespan. However, cancer therapy also induces various gastrointestinal (GI) side-effects that are dose-limiting, reduce quality of life, and potentially lead to treatment failure. Standard medical nutrition therapy for patients undergoing cancer treatment focuses on preventing weight loss and malnutrition but not reducing GI symptoms. Therefore, the objective of this study was to assess efficacy of nutrition therapy to reduce GI side-effects during cancer treatment via systematic review and meta-analysis. A systematic search was conducted in Scopus and PubMed databases. A meta-analysis was performed on articles meeting inclusion criteria to estimate the pooled effect size on GI symptoms, separated by nutrition intervention type (nutrient supplementation, oral nutrition supplement, or dietary counseling). Further subgroup analyses were conducted based on cancer type, cancer therapy, and nutrient intervention. All statistical analyses were performed in Stata/MP version 17.0 using 2-sided tests with P < 0.05 as the threshold for statistical significance. A total of 15,556 articles were captured by the search algorithm, and 139 studies met inclusion criteria for meta-analysis. Articles reported 12 different GI symptoms, resulting in 151 total meta-analyses across symptom, cancer treatment, and nutrition intervention subtypes. Meta analyses indicated that collectively (all interventions combined), nutrient supplementation reduced nausea, vomiting, and diarrhea incidence (all P < 0.001). Oral nutrition supplements had no effects on GI symptoms (all P > 0.05). Dietary counseling reduced constipation and diarrhea incidence. Although 9 individual nutrient supplementation interventions reduced 8 symptoms, probiotic supplementation had some of the strongest effects on abdominal pain, vomiting, and diarrhea incidence. This meta-analysis supports implementation of specific medical nutrition therapies to treat GI symptoms during cancer therapy and identifies those requiring additional investigation. Given the large variation in responses within and across studies, future experiments should explore personalized nutrition-based strategies to optimize treatment efficacy. This study was register at PROSPERO as 549116.