Chronic psychological stress contributes to functional disorder development, including irritable bowel syndrome (IBS). Although probiotics have shown potential in ameliorating these disorders, the precise mechanisms remain incompletely understood. The aim of this study was to elucidate the mechanism underlying the effect of Lacticaseibacillus paracasei strain Shirota (LcS) on the host anti-stress response in a colonic epithelial cell line. Expression of the stress hormone-degrading enzyme, 11 β-hydroxysteroid dehydrogenase type 2 (Hsd11b2), was suppressed by corticosterone and restored by LcS treatment. Fractionation of LcS culture supernatant revealed a derivative of carbamoyl phosphate as the key factor responsible for inducing Hsd11b2. Moreover, activation of acetylcholine receptor and inhibition of NF-κB p50 homodimer nuclear translocation were required to induce Hsd11b2 in colonic epithelial cells. These findings reveal a novel probiotic mechanism whereby an LcS metabolite triggers anti-stress responses, including Hsd11b2 induction, by modulating the acetylcholine and NF-κB pathways. This new mechanism by which probiotics can stimulate anti-stress effects in the colonic mucosa may contribute to IBS treatment.

While the immuno-modulatory effects of lactic acid bacteria (LAB) on conventional T cells are well documented, their effects on unconventional T cells, including gamma-delta (γδ) T cells, have not yet been fully characterized. Here, we show that LAB can generate regulatory γδ T cells by significantly increasing interleukin (IL)-10 production relative to stimulation with methicillin-resistant Staphylococcus aureus (MRSA), a pathogenic bacterial strain. This regulatory function subsequently attenuated inflammatory responses in intestinal epithelial cells and immune cells. Thus, LAB can induce regulatory functions in γδ T cells, which may contribute to the maintenance of intestinal health.

The intestinal environment, associated with various health benefits and disorders, including skin health, can be maintained by dietary fiber intake. Resistant maltodextrin (RMD), a water-soluble dietary fiber, improves the intestinal environment and provides various health benefits. However, its effects in humans remain unclear. Therefore, we examined the effects of ingesting 5 g of RMD per day for 8 weeks on the intestinal environment along with the possibility of concomitant skin function improvement in a randomized, double-blind, parallel, placebo-controlled study. The results showed that RMD increased fecal short-chain fatty acid (SCFA) levels and several bacteria known to be involved in SCFA production. It also alters the intestinal bacteria related to several diseases, such as inflammatory bowel disease. Furthermore, the amount of fecal SCFAs and skin moisture on the arms were correlated, indicating that RMD may improve skin health by promoting SCFA production. Overall, we demonstrate that continuous RMD intake partially alters the intestinal environment and potentially skin health.

The intestinal microbiota plays a crucial role in the onset of diarrhea and can be modulated through dietary changes. Shenling Baizhu powder (SLBZ) has been shown to regulate diarrhea. Thirty Kunming mice were randomly divided into a normal group (MCN), model group (MMD), and SLBZ group (MSLBZ). Diarrhea was induced by fatigue combined with a high-fat diet. After modeling, the MSLBZ group received 145.6 g/(kg·d) SLBZ for 7 days. Pathological examination of small intestine tissues, along with measurements of interleukin 6 (IL-6), interleukin 17 (IL-17), immunoglobulin A (sIgA), and mucin 2 (Muc2) levels, were conducted. The intestinal mucosa was extracted for high-throughput sequencing of 16S rRNA. In the MMD group, intestinal damage, lymphocyte infiltration, decreased sIgA, diarrhea, and a significant increase in Helicobacter were observed compared with the MCN group. After SLBZ treatment, the MSLBZ group exhibited improved body weight, reduced intestinal damage, decreased levels of IL-6, increased sIgA, and alleviated diarrhea. Compared with the MMD group, the abundance of Duncaniella freteri was significantly higher, while Helicobacter was markedly reduced. Correlation analysis showed that Duncaniella freteri was positively correlated with sIgA and Muc2 and negatively correlated with IL-6 and IL-17. SLBZ alleviates intestinal mucosal damage, reduces pro-inflammatory cytokines, enhances sIgA production, and restores the microbiota balance in mice with diarrhea.

In non-IgE-mediated food allergy, food protein-induced enteropathy (FPE) can be evoked by the Th2 response. Some reports show that either Th2-biased immune responses or gut microbial dysbiosis can exacerbate food-allergic gastrointestinal inflammation. Nevertheless, it remains unclear whether gut microbiota directly affect Th2-biased immune responses involving FPE. To address this issue, we used OVA23-3 × BALB/cA mice, which is an FPE-like model. Feeding the mice an egg-white diet (EW) induced excessive Th2-type immune responses in CD4⁺ T cells in the mesenteric lymph nodes (MLNs), resulting in weight loss and enteropathy. Firstly, we compared specific pathogen-free (SPF) OVA23-3 × BALB/cA mice with germ-free (GF) OVA23-3 × BALB/cA mice when fed an EW diet. Symptoms shown in SPF mice were attenuated in GF mice, suggesting that gut microbiota may contribute to exacerbating symptoms. Additionally, we orally administered broad-spectrum antibiotics (Abx) to OVA23-3×BALB/cA mice and analyzed the gut microbiota. Compared with a no-Abx administration group, we found that Abx administration significantly altered the alpha and beta diversity of the gut microbiota in EW-fed mice. The presence of Alloprevotella, Bacteroides, and Muribaculaceae was reduced to approximately 10%. Both weight loss and enteropathy in EW-fed mice were ameliorated after Abx administration. Furthermore, administration of Abx to the EW-fed group improved the Th1/Th2 balance in MLN cells and decreased the mRNA expression of IL-33 and the aryl hydrocarbon receptor in the jejunum. These results suggest that some members of the gut microbiota disturb Th1/Th2 responses in the MLN, by affecting the small intestinal epithelium, thereby exacerbating Th2-biased responses and inducing food-allergic enteropathy.

Listeria monocytogenes is a highly lethal foodborne pathogen that exhibits strain-dependent differences in virulence. Infection begins with traversal of the intestinal barrier through a two-step process involving adhesion to intestinal epithelial cells followed by intracellular invasion. In this study, Caco-2 cells were used to investigate these early infection events in 25 Japanese L. monocytogenes isolates (9 human clinical, 14 food-derived, and 2 environmental isolates) and 1 reference clinical strain (ScottA). We examined the genetic integrity of key adhesion- and invasion-related virulence genes (lap, fbpA, inlA, and inlB) and their relationships with adhesion and invasion phenotypes. Premature stop codons (PMSCs) were identified in inlA in 11 isolates and in inlB in 15 isolates. PMSCs in inlA were absent from all clinical isolates and predominantly found in serotypes 1/2a and 1/2c, which are rarely associated with clinical listeriosis. Also, three novel inlA PMSC variants were identified. Adhesion to Caco-2 cells was relatively uniform among isolates (5.87–6.88 log₁₀ colony-forming units [CFU]/mL), whereas invasion varied markedly (2.74–6.27 log₁₀ CFU/mL). Isolates carrying PMSCs in inlA consistently showed reduced invasion (<4 log₁₀ CFU/mL), whereas isolates lacking PMSCs exhibited significantly higher invasion (>5 log₁₀ CFU/mL). Western blot analysis confirmed the absence of full-length InlA in PMSC-containing isolates. Antibody-mediated inhibition of InlA produced a dose-dependent reduction in invasion, confirming the critical role of InlA in epithelial cell invasion. These findings demonstrate that the PMSCs in inlA are a key determinant of invasion capacity and may partly explain the serotype bias observed among human clinical isolates. Our results highlight the importance of virulence factor-based risk assessment for L. monocytogenes, rather than treating all strains as equally pathogenic.

Hyperuricemia (HUA) is widespread, and since conventional long-term treatments can be toxic, safer multi-target alternatives are required. Here, we tested a naturally derived synbiotic pairing of the uricolytic probiotic Lactobacillus gasseri SYP-B4432 with a polyphenol-rich Rumex hanus by. extract in a mouse model of hyperuricemia. In just five weeks of daily treatment, the combination reduced serum uric acid by 57.86%, suppressed serum xanthine oxidase activity by 14.31%, and restored the Bacteroidetes/Firmicutes ratio while lowering pro-inflammatory cytokines and attenuating renal histopathology. Importantly, no hepatic/renal impairment or body weight abnormalities were detected, confirming the safety of this intervention. Collectively, the probiotic–herbal duo alleviates HUA through the synergy of three modes of action: curtailing uric acid synthesis (via XOD inhibition), reshaping gut microbiota (to enhance UA excretion), and resolving renal inflammation (via cytokine modulation). This natural, safe, and multi-target synbiotic provides a clinically translatable strategy that may address the side effect limitations of conventional hyperuricemia drugs.

The gut microbiome is home to trillions of microorganisms, bacteria, fungi, parasites, and viruses, that coexist harmoniously in healthy individuals. However, disruptions to this balance, such as dietary changes, can lead to dysbiosis, affecting normal gut functions. With the recent urbanization of the Philippine countryside, western diets are becoming increasingly common and may alter the gut microbiome, predisposing even children to metabolic disorders. Hence, this cross-sectional study aimed to determine the association of a westernized diet with the gut microbiome profiles of school-aged children in rural and urban communities in Leyte, Philippines and assess their association with childhood obesity. Based on interviews, physical examinations, and dietary questionnaires, similar anthropometric traits were observed among the participants. Macronutrient analysis revealed that urban children consumed more fats and had higher total energy intakes, revealing a more westernized type of diet, while rural children had higher carbohydrate and fiber-rich intakes. This dietary contrast significantly influences the gut microbiome profile, with rural children having greater microbial diversity and higher levels of fiber-fermenting bacteria from the Prevotellaceae family, whereas urban children harbored more Bacteroides and Ligilactobacillus ruminis. Correlation analysis linked fat-rich diets with reduced abundances of fiber-fermenting bacteria, such as Succinivibrio and Segatella. Participants were also sub-grouped based on their BMI-for-age classification. The urban overweight-obese group exhibited a higher intake of dietary fats and a distinct microbiome profile characterized by taxa previously reported in obesity-associated gut communities. These findings suggest emerging risks for the gut health of Filipino children undergoing nutrition transition and may offer insights for shaping future nutrition initiatives that support their well-being.

This study aimed to investigate the intestinal microecological mechanisms underlying the effects of Sishen Pill (SSP) on diarrhea-predominant irritable bowel syndrome (IBS-D) with Spleen-Kidney Yang Deficiency Syndrome, thereby providing experimental evidence for clinical management. Murine models of IBS-D characterized by Spleen-Kidney Yang insufficiency were established in SPF-grade female Kunming mice by Folium senna-adenine gavage in conjunction with restraint-tail clamping. Experimental groups received SSP decoction or pinaverium bromide suspension. Intestinal morphological changes were assessed via Alcian blue staining. The concentrations of serum D-lactate and diamine oxidase were measured through enzyme-linked immunosorbent assay. The intestinal mucosal microbiota was analyzed using 16S rRNA gene sequencing. The model mice exhibited reduced anal temperatures, diarrhea, weight loss, intestinal mucosal barrier injury, and altered mucosal microbiota. SSP treatment alleviated these abnormalities, decreased serum D-LA and DAO levels, and improved the intestinal mucosal structure. Microbiota analysis identified Alkaliphilus as a potential genus associated with SSP intervention, while Streptococcus and Maribacter were correlated with intestinal barrier indicators. These findings suggest that SSP may improve IBS-D with Spleen-Kidney Yang Deficiency by modulating the intestinal mucosal microbiota and restoring mucosal barrier function.

Intestinal barrier dysfunction is a key pathological factor in various chronic diseases, including inflammatory bowel disease. This study compared the barrier-protective effects and mechanisms of two heat-treated plant-derived lactic acid bacteria (P-LAB) strains, Lactiplantibacillus plantarum LOC1 isolated from tea leaves and Lacticaseibacillus paracasei RO24 isolated from traditional Japanese pickles, using lipopolysaccharide (LPS)-stimulated intestinal epithelial cell models. Barrier integrity was evaluated in Caco-2 and HT29 cells by measuring transepithelial electrical resistance (TEER) and paracellular permeability to Lucifer Yellow, together with analyses of tight junction–related gene expression, inflammatory cytokines, and global proteomic profiling integrated with Ingenuity Pathway Analysis. LPS exposure significantly impaired barrier function in both cell lines. Pretreatment with either strain significantly suppressed LPS-induced increases in paracellular permeability, whereas TEER recovery was strain- and cell-line-dependent. L. plantarum LOC1 effectively restored TEER in Caco-2 cells, while L. paracasei RO24 exerted significant protective effects primarily in HT29 cells. Mechanistic analyses revealed distinct modes of action between the two strains. L. plantarum LOC1 showed broad anti-inflammatory activity and maintained the expression of JAM-A and occludin, representing a comprehensive barrier-protective strategy. In contrast, L. paracasei RO24 selectively preserved Claudin-1, Claudin-3, and Claudin-7, indicating a structural reinforcement strategy. Proteomic and pathway analyses confirmed reactivation of tight junction signaling by both strains. These findings indicate that heat-treated P-LAB strains can exert strain-specific protective effects on intestinal epithelial barrier function under the present experimental conditions.

The intestinal barrier plays a crucial role in host metabolic and immune homeostasis; however, its integrity can be disrupted by factors such as lipopolysaccharides, inflammatory cytokines, and oxidative stress. Although Bifidobacterium species are considered beneficial members of the gut microbiota, their strain-specific effects on epithelial barrier integrity and the underlying mechanisms remain incompletely understood. We investigated the protective effects of four heat-killed strains of bifidobacteria, B. pseudocatenulatum YIT 11057, B. adolescentis YIT 13021, B. bifidum YIT 10347, and B. breve YIT 4014, on intestinal barrier function using T84 monolayers, a widely used in vitro model of the intestinal epithelium that retains many colon-like properties. Among the tested strains, only B. adolescentis YIT 13021 (YIT 13021) consistently protected against barrier disruption induced by lipopolysaccharide (LPS), oxidative stress, and inflammatory cytokines, highlighting species-enriched but strain-dependent functional properties within B. adolescentis. YIT 13021 preserved tight junction integrity in association with preserved localization of zonula occludens-1 and attenuated stimulus-induced nuclear localization of nuclear factor-kappa B. Furthermore, live YIT 13021 exerted superior barrier-protective effects than its heat-killed counterpart, and its protective efficacy was further increased when cultured in the presence of starch, suggesting that metabolic activity and substrate availability influence functional outcomes. These findings demonstrate functional heterogeneity among Bifidobacterium strains, provide insights into potential mechanisms underlying microbiota-mediated modulation of epithelial integrity, and identify B. adolescentis YIT 13021 as a promising candidate for supporting intestinal barrier homeostasis.