Skip to content
Open access

Microbiome-mediated Biotransformation of Human Lactoferrin (effera®) Enhances Epithelial Barrier Function in an Ex Vivo Adult Model

Aug 2026 · bioRxiv · 0 citations
Biology

TL;DR

It is demonstrated that microbial biotransformation enhances the biological activity of effera®, linking increased microbial metabolism with improved epithelial barrier integrity and modulation of inflammatory signaling.

Read PDF

Similar papers

Open access Jul 2026

Milk-delivered postbiotics from Bifidobacterium animalis subsp. lactis BB-12 modulate the gut microbiota-SCFA-immune axis in rats compared to probiotic delivery.

Despite growing interest in postbiotics as stable alternatives to probiotics, their efficacy when delivered through food matrices and their integrated effects on the gut microbiota-metabolite-immune axis remain poorly understood. This study investigated whether postbiotic-enriched milk derived from Bifidobacterium animalis subsp. lactis BB-12 can functionally modulate host-microbiota interactions in vivo, in comparison with probiotic milk and appropriate controls. Postbiotics, consisting of heat-inactivated bacterial cells and their metabolites, were generated by thermal inactivation (95 °C for 30 min) and incorporated into UHT milk at a level equivalent to cultures containing 109 CFU mL-1 prior to heat inactivation. Following a 28-day intervention in healthy rats, gut microbiota composition, cecal short-chain fatty acids (SCFAs), and systemic immune parameters were comprehensively evaluated. Postbiotic delivery through a milk matrix selectively reshaped gut microbial composition without altering overall diversity, indicating targeted ecological modulation. Notably, postbiotics reduced Bacteroidota abundance and shifted the Bacillota/Bacteroidota ratio toward a more balanced profile, accompanied by enrichment of taxa associated with carbohydrate fermentation and microbial cross-feeding. These compositional changes translated into a significant increase in SCFA production, particularly butyrate (p < 0.05), highlighting enhanced metabolic functionality of the gut microbiota. Importantly, postbiotic supplementation induced a systemic immune shift toward a Th1-oriented response, with increased IFN-γ and IL-2 levels and reduced IL-4, IL-13, and IgE, alongside elevated IgA, IgG, and IgM concentrations. Spearman correlation analysis confirmed strong functional links connecting specific microbial shifts to both SCFA profiles and cytokine modulations. In several parameters, postbiotic milk exhibited comparable or superior effects relative to probiotic milk. Collectively, these findings demonstrate that food-delivered B. lactis BB-12 postbiotics can reprogram the gut microbiota-SCFA-immune axis in vivo, supporting their potential as a stable, next-generation functional dairy strategy.

E. Akan, Esra Orenlili Yaylagul, Adem Yavaş et al. · 0 citations
Open access Aug 2026

Mushroom β-Glucan as a Novel Prebiotic: Enhancing Recovery of the Post-Antibiotic Gut Microbiota over 60 Days

Antibiotic-induced dysbiosis can cause persistent alterations in gut microbial composition and fermentative metabolism, yet the long-term role of mushroom β-glucan-based prebiotics in supporting post-antibiotic microbiota modulation remains poorly defined. To address this gap, the present study evaluated the modulatory effects of ColonX, a mushroom β-glucan-based formulation, during a 60-day in vitro simulation of post-antibiotic gut microbiota modulation. Quantitative PCR (qPCR) was used to monitor key bacterial groups, while UHPLC-DAD analysis was applied to characterize fermentation-derived organic acids. ColonX administration produced a selective, time-dependent increase in Bifidobacterium spp., with limited effects on Lactobacillus spp. and no stimulation of opportunistic bacteria such as Escherichia coli. This response became more evident after prolonged administration, suggesting progressive adaptation of the dysbiotic microbiota. Metabolomic analysis showed increased production of short-chain fatty acids and other fermentation-derived organic acids, indicating enhanced saccharolytic activity and functional metabolic remodeling. The accumulation of succinic acid further suggested ongoing microbial metabolic restructuring during recovery, while comparison with individual excipients indicated that resistant dextrin contributed to the fermentative response. Overall, this study addresses an important gap by linking prolonged mushroom β-glucan administration with both taxonomic modulation and functional metabolic recovery markers in a post-antibiotic dysbiosis model. These findings support ColonX as a promising nutraceutical strategy to promote gut microbiota restoration following antibiotic exposure.

Emanuel Vamanu, Laura-Dorina Dinu, E. Geană et al. · 0 citations
Jul 2026

In vivo absorption in mice and fecal fermentation by human gut microbiota: impacts on gut microbiota and short-chain fatty acids production.

BACKGROUND Current understanding of the biological activities and metabolism of raffinose remains limited. This study aimed to elucidate its digestive behavior and anti-allergic potential by integrating fluorescence imaging in mice, in vitro digestion simulation, human fecal fermentation, and RBL-2H3 cells detection. RESULTS The results showed that following oral gavage in mice, raffinose was primarily distributed in the gastrointestinal tract and reached the colon within 2-6 h. In addition, raffinose was hardly degraded during in vitro simulated gastric and intestinal digestion. Analysis of human fecal microbiota demonstrated that microbial richness and diversity were lower in food-allergic individuals than in healthy individuals. In the in vitro fermentation system using human fecal samples, raffinose supplementation increased short-chain fatty acid concentrations in the group involving fecal fermentation from healthy volunteers with raffinose. Furthermore, raffinose inhibited the growth of Escherichia-Shigella and Weissella. In the RBL-2H3 cell degranulation model, raffinose promoted cell proliferation, suppressed degranulation, and reduced the release of β-hexosaminidase and histamine, demonstrating its anti-degranulation capacity. CONCLUSION Our results verify that raffinose is indigestible in the upper gastrointestinal tract using a mouse model. It modulates gut microbiota and short-chain fatty acids in in vitro human fecal fermentation systems and produces anti-allergic effects in cell models. These findings provide a foundation for expanding the applications of raffinose in deep processing as a value-added functional product. © 2026 Society of Chemical Industry.

Jing Ma, Jian Yu, Zhen Liu et al. · 0 citations
Review Open access Jul 2026

1-Kestose as a Candidate Precision Bioactive Component: From GH32-Dependent Gut Microbiota Regulation to Human Health Enhancement

Gut microbiota dysbiosis is implicated in diverse intestinal and systemic disorders, and prebiotics offer a practical strategy to modify host–microbe interactions. This review evaluates 1-kestose as a candidate precision bioactive component by integrating its chemical structure, enzymatic production, gastrointestinal fate, GH32-dependent microbial utilization, human evidence, and qPCR-based response monitoring. Many commercial fructooligosaccharides contain molecules with different degrees of polymerization, complicating structure–function interpretation. In contrast, 1-kestose is a high-purity trisaccharide fructooligosaccharide and the shortest member of the inulin-type fructans. By comparing 1-kestose with long-chain inulin, we examine how fructan chain length may influence colonic fermentation kinetics, substrate availability, and tolerability. We then discuss the role of GH32 substrate specificity in the selective microbial utilization of 1-kestose and related fructooligosaccharides, particularly by bifidobacteria and representative butyrate producers. Next, we review the mechanistic rationale and preclinical evidence for co-administration of 1-kestose and long-chain inulin. Human intervention studies have evaluated 1-kestose across gastrointestinal, metabolic, immune-related, neonatal, oncological, and bowel-habit contexts, with emerging evidence of potential benefits. One healthy-adult trial has also evaluated co-administration with long-chain inulin, although direct comparative trials remain an important future priority. Finally, we propose a research framework that integrates high-purity 1-kestose, GH32-dependent microbial selectivity, and qPCR-based baseline stratification and response monitoring. Prospective, independently replicated trials are needed to establish clinical effectiveness and determine the value of biomarker-guided intervention and combination strategies.

Tadashi Fujii, Hideaki Takahashi, Eizaburo Ohno et al. · 0 citations
Open access Jul 2026

Microbiota-dependent biotransformation of apiin drives butyrate-associated protection against colitis.

Dietary glycosides represent an important class of microbiota-responsive food components with potential benefits for intestinal health, yet their biotransformation and functional mechanisms remain incompletely understood. Here, we investigated the protective effects of apiin (apigenin-7-O-apiosylglucoside), a naturally occurring flavone glycoside abundant in plant-based foods, against dextran sulfate sodium (DSS)-induced colitis. We demonstrate that apiin is resistant to host digestion but undergoes efficient microbial deglycosylation in the distal intestine, yielding the bioactive aglycone apigenin. Apiin administration was associated with alleviation of colitis severity, as evidenced by improved clinical and histopathological outcomes, reduced pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6), and restoration of intestinal barrier integrity. Integrative multi-omics analyses revealed that apiin reshaped gut microbiota composition and function, leading to enhanced production of the short-chain fatty acid butyrate. This metabolic shift was associated with G protein-coupled receptors (GPR41 and GPR43) and PPARγ signaling, as well as NF-κB-driven inflammatory responses. Importantly, fecal microbiota transplantation recapitulated the protective effects of apiin, confirming a microbiota-dependent mechanism. Collectively, our findings identify apiin as a microbiota-dependent pro-flavonoid whose colonic biotransformation into apigenin and butyrate-associated signaling may contribute to its anti-inflammatory activity.

Zhenning Guo, Meiqi Zhao, Yuwei Wu et al. · 0 citations
Open access Aug 2026

Lactoferrin Hydrolysate Mitigates Azoxymethane/Dextran Sulfate Sodium–Induced Colon Cancer by Modulating Gut Microbiota and Microbial Metabolites

Colon cancer is one of the most common malignant tumors worldwide and is associated with high morbidity and mortality. Conventional treatments are typically administered at advanced stages and often lead to severe adverse effects. Therefore, developing safe and effective nutritional interventions from natural food sources is of great importance for the prevention and management of colon cancer. Dairy-derived protein hydrolysates have received increasing attention as functional food components due to their biological activities and favorable safety profiles. In this study, lactoferrin (LF) was hydrolyzed using alkaline protease to obtain lactoferrin hydrolysate (LFH). LFH was administered to mice with azoxymethane/dextran sulfate sodium-induced colon cancer to evaluate its protective effects. LFH markedly alleviated colonic tissue injury, reduced serum levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, and decreased the expression of tumor markers CEA, CA19-9, as well as the proliferation marker Ki-67, thereby inhibiting tumor progression. At the molecular level, LFH downregulated key genes in the Wnt/β-catenin pathway, including c-Myc, β-catenin, and Cyclin D1. Furthermore, LFH upregulated pro-apoptotic genes Bax, caspase-9, caspase-3, and p53, while downregulating anti-apoptotic genes Bcl-2 and Bcl-xl, suggesting enhanced apoptotic responses in tumor cells. LFH also significantly improved gut microbiota composition by reducing harmful bacteria such as Bacillus, Enterorhabdus, and Odoribacter, while increasing beneficial genera including Ruminococcus and Eubacterium_siraeum_group. Correspondingly, LFH elevated several gut microbial metabolites such as Chrysogine, Agmatine, 5′-Deoxy-5-Fluorocytidine, and Glutamyl-γ-Glutamate. Overall, this study provides new insights into the biological effects of LFH on colon cancer and supports its potential application in the development of LFH-based functional foods.

Han-Jun Jiang, Xue Deng, Jing Yang et al. · 0 citations

We use cookies to run the site and, with your consent, for analytics and to show ads. See our Cookie Policy.