Search Results (13)

Background: Irritable bowel syndrome (IBS) significantly impairs the lifestyle and quality of life of the global population. However, the underlying pathophysiological mechanisms remain largely elusive. While conventional pharmacological approaches show limited therapeutic efficacy, emerging microbiota-targeted dietary interventions present promising alternatives. Objectives: The present study aimed to elucidate the molecular mechanisms by which a synbiotic mitigates IBS and associated colonic dysfunctions in C57BL/6 mice. Methods: The mouse model was induced by a Citrobacter rodentium (C. rodentium) infection combined with water avoidance stress (WAS). Galacto-oligosaccharides (GOS) were identified as the optimal carbon source for the growth of Lactobacillus plantarum ZYC501 (L. plantarum ZYC501), leading to the establishment of the synbiotic formulation. Results: The 32-day synbiotic intervention, consisting of L. plantarum ZYC501 (1 × 10⁹ CFU/day) and GOS (10 g/L, w/w), significantly alleviated colonic transit dysfunction, visceral hypersensitivity, and anxiety-like behaviors in IBS mice. The synbiotic treatment significantly inhibited the expression levels of histamine, mast cell tryptase, and prostaglandin E2 (PGE2) (p < 0.05). The synbiotic also suppressed colonic inflammation by reducing the levels of lipopolysaccharide (LPS), TNF-α, and IL-6 (p < 0.05). Moreover, the synbiotic increased the expression of MUC2 and the production of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate (p < 0.05). In terms of gut microbiota modulation, the synbiotic reshaped the gut microbiota composition, increasing the abundance of Lactobacillus and Akkermansia while decreasing the levels of Helicobacter and Saccharibacteria. Correlation analysis further revealed a strong association among SCFAs, colonic inflammation, and the gut microbiota. Conclusions: In conclusion, the synbiotic composed of L. plantarum ZYC501 and GOS effectively alleviates IBS and associated colonic dysfunctions by modulating the gut microbiota, reducing mast cell hyperactivity, and enhancing colonic barrier integrity. These findings provide a theoretical basis for developing gut microbiota-targeted dietary interventions for the management of IBS and improvement in gut health. Full article

Oligosaccharides containing galactosyl moieties belong to two main groups: raffinose family oligosaccharides (RFO, α-GOS) and lactose-type β-galactooligosaccharides (β-GOS), both well-known for their prebiotic effect. The present review investigates the vast amounts of recent research on the structures of GOS and their beneficial impact. It focuses on the molecular interactions between GOS and probiotics in vitro and in vivo, the enzymology of the processes, and the genetic prerequisites for the synthesis and degradation of GOS by probiotic bacteria. The preferences of probiotic strains belonging to the Bifidobacterium and Lactobacillus genera are elucidated to form and degrade GOS of a certain length, structure, and linkages between monomers. A brief overview of the industrial production of β-GOS by natural and recombinant strains included the methods and production efficiency evaluation. Full article

(1) Exposure of intestinal epithelial cells to heat and hypoxia causes a (heat) stress response, resulting in the breakdown of epithelial integrity. There are indications that several categories of nutritional components have beneficial effects on maintaining the intestinal epithelial integrity under stress conditions. This study evaluated the effect of nine nutritional components, including non-digestible oligosaccharides (galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS), chitosan oligosaccharides (COS)), antioxidants (α-lipoic acid (ALA), resveratrol (RES)), amino acids (l-glutamine (Glu), l-arginine (Arg)) and polyunsaturated fatty acids (PUFAs) (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)), on heat/hypoxia-induced epithelial injury. (2) Two human colonic cell lines, Caco-2 and HT-29, were co-cultured and pre-treated with the nutritional components for 48 h. After pre-treatment, the cells were exposed to heat/hypoxia (42 °C, 5% O₂) for 2 h. Epithelial integrity was evaluated by measuring trans-epithelial electrical resistance (TEER), paracellular Lucifer Yellow (LY) permeability, and tight junction (TJ) protein expression. Heat stress and oxidative stress levels were evaluated by determining heat-shock protein-70 (HSP-70) expression and the concentration of the lipid peroxidation product malondialdehyde (MDA). (3) GOS, FOS, COS, ALA, RES, Arg, and EPA presented protective effects on epithelial damage in heat/hypoxia-exposed Caco-2/HT-29 cells by preventing the decrease in TEER, the increase in LY permeability, and/or decrease in TJ proteins zonula occludens-1 (ZO-1) and claudin-3 expression. COS, RES, and EPA demonstrated anti-oxidative stress effects by suppressing the heat/hypoxia-induced MDA production, while Arg further elevated the heat/hypoxia-induced increase in HSP-70 expression. (4) This study indicates that various nutritional components have the potential to counteract heat/hypoxia-induced intestinal injury and might be interesting candidates for future in vivo studies and clinical trials in gastrointestinal disorders related to heat stress and hypoxia. Full article

In several mice inflammatory models, human milk oligosaccharides (HMOs) were shown to protect the intestinal barrier by promoting mucin secretion and suppressing inflammation. However, the functions of the individual HMOs in enhancing mucin expression in vivo have not been compared, and the related mechanisms are not yet to be clarified. In this study, we investigated the modulatory effects of 2′-fucosyllactose (2′-FL), 3′-sialyllactose (3′-SL), galacto-oligosaccharide (GOS) and lactose (Lac) on goblet cells’ functions in vitro. The appropriate dosage of the four chemicals was assessed in LS174T cells using the CCK-8 method. Then they were supplemented into a homeostasis and inflammatory environment to further investigate their effects under different conditions. Mucin secretion-related genes, including mucin 2 (MUC2), trefoil factor family 3 (TFF3), resistin-like β (RETNLB), carbohydrate sulfotransferase 5 (CHST5) and galactose-3-O-sulfotransferase 2 (GAL3ST2), in LS174T cells were detected using quantitative RT-qPCR. The results showed that 2′-FL (2.5 mg/mL, 72 h) was unable to increase MUC2 secretion in a steady-state condition. Comparatively, it exhibited a greater ability to improve mucin secretion under an inflammatory condition compared with GOS, demonstrated by a significant increase in TFF3 and CHST5 mRNA expression levels (p > 0.05). However, 3′-SL and Lac exhibited no effects on mucin secretion. To further investigate the underlying mechanism via which 2′-FL enhanced goblet cells’ secretion function, the NOD-like receptor family pyrin domain containing 6 (NLRP6) gene, which is closely related to MUC2 secretion, was silenced using the siRNA method. After silencing the NLRP6 gene, the mRNA expression levels of MUC2, TFF3 and CHST5 in the (2′-FL + tumor necrosis factor α (TNF-α) + NLRP6 siRNA) group were significantly decreased compared with the (2′-FL + TNF-α) group (p > 0.05), indicating that NLRP6 was essential for MUC2 expression in goblet cells. We further found that 2′-FL could significantly decrease toll-like receptor 4 (TLR4, p < 0.05), myeloid differential protein-88 (MyD88, p < 0.05) and nuclear factor kappa-B (NF-κB, p < 0.05) levels in LS174T inflammatory cells, even when the NLRP6 was silenced. Altogether, these results indicated that in goblet cells, 2′-FL exerts its function via multiple processes, i.e., by promoting mucin secretion through NLRP6 and suppressing inflammation by inhibiting the TLR4/MyD88/NF-κB pathway. Full article

The effects of natural and synthetic galactooligosaccharides (GOS) on inflammation were explored by investigating the structure-activity relationship between the degree of GOS polymerization and in vitro anti-inflammatory activity, together with the potential underlying mechanism of their anti-inflammatory effects. The results demonstrated that GOS had strong anti-inflammatory effects in lipopolysaccharide (LPS)-induced RAW264.7 macrophages, including the inhibition of nitric oxide production and the reduced expression of pro-inflammatory mediators (interleukin-1β, interleukin-6, and tumor necrosis factor α), induced nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and proteins related to the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway. GOS4, which has the highest degree of polymerization, exerted the strongest anti-inflammatory activity among the GOS examined. More importantly, our findings confirmed the anti-inflammatory effects of GOS on RAW264.7 macrophages via the TLR4/NF-κB pathway. Our experimental results could provide further support for the exploration of GOS in human nutrition and health. Full article

The leading cause of gastroenteritis among young children worldwide is the Group A rotaviruses (RV), which produce a wide range of symptoms, from a limited diarrhea to severe dehydration and even death. After an RV infection, immunity is not complete and less severe re-infections usually occur. These infections could be ameliorated by nutritional interventions with bioactive compounds, such as prebiotics. The aim of this research was to study the impact of a particular galactooligosaccharide (B-GOS) on the RV symptomatology and immune response during two consecutive infections. Lewis neonatal rats were inoculated with SA11 (first RV infection) on day 6 of life and with EDIM (second RV infection) on day 17 of life. B-GOS group was administered by oral gavage with a daily dose of B-GOS between days three to nine of life. Clinical and immunological variables were assessed during both infective processes. In the first infection, after the prebiotic intervention with B-GOS, a lower incidence, duration, and overall severity of the diarrhea (p < 0.05) was observed. In addition, it improved another severity indicator, the fecal weight output, during the diarrhea period (p < 0.05). The second RV infection failed in provoking diarrhea in the groups studied. The immune response during first infection with SA11 was not affected by B-GOS administration and had no impact on second infection, but the prebiotic intervention significantly increased IFN-γ and TNF-α intestinal production after the second infection (p < 0.05). In summary, B-GOS supplementation is able to reduce the incidence and severity of the RV-associated diarrhea and to influence the immune response against RV infections. Full article

Urbanization influences our lifestyle, especially in fast-paced environments where we are more prone to stress. Stress management is considered advantageous in terms of longevity. The use of probiotics for psychological treatment has a small amount of diverse proven evidence to support this. However, studies on stress management in stressed subjects using synbiotics are still limited. The present study aimed to investigate the effects of synbiotics on stress in the Thai population. A total of 32 volunteers were enrolled and screened using a Thai Stress Test (TST) to determine their stress status. Participants were divided into the stressed and the non-stressed groups. Synbiotics preparation comprised a mixture of probiotics strains in a total concentration of 1 × 10¹⁰ CFU/day (5.0 × 10⁹ CFU of Lactobacillus paracasei HII01 and 5.0 × 10⁹ CFU of Bifidobacterium animalis subsp. lactis) and 10 g prebiotics (5 g galacto-oligosaccharides (GOS), and 5 g oligofructose (FOS)). All parameters were measured at baseline and after the 12th week of the study. In the stressed group, the administration of synbiotics significantly (p < 0.05) reduced the negative scale scores of TST, and tryptophan. In the non-stressed group, the synbiotics administration decreased tryptophan significantly (p < 0.05), whereas dehydroepiandrosterone sulfate (DHEA-S), tumor necrosis factor-α (TNF-α), 5-hydroxyindoleacetic acid (5-HIAA), and short-chain fatty acids (SCFAs), acetate and propionate were increased significantly (p < 0.05). In both groups, cortisol, and lipopolysaccharide (LPS) were reduced, whereas anti-inflammatory mediator interleukin-10 (IL-10) and immunoglobulin A (IgA) levels were increased. In conclusion, synbiotics administration attenuated the negative feelings via the negative scale scores of TST in stressed participants by modulating the HPA-axis, IL-10, IgA, and LPS. In comparison, synbiotics administration for participants without stress did not benefit stress status but showed remodeling SCFAs components, HPA-axis, and tryptophan catabolism. Full article

Prebiotic galacto-oligosaccharides (GOS) were shown to support mucosal immune development by enhancing regulatory-type Th1 immune polarization induced by synthetic CpG oligodeoxynucleotides (TLR9 agonist mimicking a bacterial DNA trigger). Epithelial-derived galectin-9 was associated with these immunomodulatory effects. We aimed to identify the most active fractions within GOS based on the degree of polymerization (DP), and to study the immunomodulatory capacities of DP3-sized β-3′galactosyllactose (β-3′GL) using a transwell co-culture model of human intestinal epithelial cells (IEC) and activated peripheral blood mononuclear cells (PBMC). IEC were apically exposed to different DP fractions of GOS or β-3′GL in the presence of CpG, and basolaterally co-cultured with αCD3/CD28-activated PBMC, washed, and incubated in fresh medium for IEC-derived galectin analysis. Only DP3-5 in the presence of CpG enhanced galectin-9 secretion. DP3-sized β-3′GL promoted a regulatory-type Th1 response by increasing IFNγ and IL-10 or galectin-9 concentrations as compared to CpG alone. In addition, IEC-derived galectin-3, -4, and -9 secretion was increased by β-3′GL when combined with CpG. Therefore, the GOS DP3-5 and most effectively DP3-sized β-3′GL supported the immunomodulatory properties induced by CpG by enhancing epithelial-derived galectin secretion, which, in turn, could support mucosal immunity. Full article

Acute kidney injury (AKI) is a sudden episode of kidney damage that commonly occurs in patients admitted to hospitals. To date, no ideal treatment has been developed to reduce AKI severity. Oligo-fucoidan (FC) interferes with renal tubular cell surface protein cluster of differentiation 44 (CD44) to prevent renal interstitial fibrosis; however, the influence of oligosaccharides on AKI remains unknown. In this study, FC, galacto-oligosaccharide (GOS), and fructo-oligosaccharide (FOS) were selected to investigate the influence of oligosaccharides on AKI. All three oligosaccharides have been proven to be partially absorbed by the intestine. We found that the oligosaccharides dose-dependently reduced CD44 antigenicity and suppressed the hypoxia-induced expression of CD44, phospho-JNK, MCP-1, IL-1β, and TNF-α in NRK-52E renal tubular cells. Meanwhile, CD44 siRNA transfection and JNK inhibitor SP600125 reduced the hypoxia-induced expression of phospho-JNK and cytokines. The ligand of CD44, hyaluronan, counteracted the influence of oligosaccharides on CD44 and phospho-JNK. At 2 days post-surgery for ischemia–reperfusion injury, oligosaccharides reduced kidney inflammation, serum creatine, MCP-1, IL-1β, and TNF-α in AKI mice. At 7 days post-surgery, kidney recovery was promoted. These results indicate that FC, GOS, and FOS inhibit the hypoxia-induced CD44/JNK cascade and cytokines in renal tubular cells, thereby ameliorating AKI and kidney inflammation in AKI mice. Therefore, oligosaccharide supplementation is a potential healthcare strategy for patients with AKI. Full article

Animal digestive systems host microorganism ecosystems, including integrated bacteria, viruses, fungi, and others, that produce a variety of compounds from different substrates with healthy properties. Among these substrates, α-galacto-oligosaccharides (GOS) are considered prebiotics that promote the grow of gut microbiota with a metabolic output of Short Chain Fatty Acids (SCFAs). In this regard, we evaluated Lupinus albus GOS (LA-GOS) as a natural prebiotic using different animal models. Therefore, the aim of this work was to evaluate the effect of LA-GOS on the gut microbiota, SCFA production, and intestinal health in healthy and induced dysbiosis conditions (an ulcerative colitis (UC) model). Twenty C57BL/6 mice were randomly allocated in four groups (n = 5/group): untreated and treated non-induced animals, and two groups induced with 2% dextran sulfate sodium to UC with and without LA-GOS administration (2.5 g/kg bw). We found that the UC treated group showed a higher goblet cell number, lower disease activity index, and reduced histopathological damage in comparison to the UC untreated group. In addition, the abundance of positive bacteria to butyryl-CoA transferase in gut microbiota was significantly increased by LA-GOS treatment, in healthy conditions. We measured the SCFA production with significant differences in the butyrate concentration between treated and untreated healthy groups. Finally, the pH level in cecum feces was reduced after LA-GOS treatment. Overall, we point out the in vivo health benefits of LA-GOS administration on the preservation of the intestinal ecosystem and the promotion of SCFA production. Full article

Despite the nutritional properties of alfalfa, its production is mainly for animal feed and it is undervalued as a food source. In this study, the valorization of alfalfa as a potential source of bioactive carbohydrates [inositols, α-galactooligosaccharides (α-GOS)] is presented. A Box–Behnken experimental design was used to optimize the extraction of these carbohydrates from leaves, stems, and seeds of alfalfa by solid–liquid extraction (SLE) and microwave-assisted extraction (MAE). Optimal extraction temperatures were similar for both treatments (40 °C leaves, 80 °C seeds); however, SLE required longer times (32.5 and 60 min vs. 5 min). In general, under similar extraction conditions, MAE provided higher yields of inositols (up to twice) and α-GOS (up to 7 times); hence, MAE was selected for their extraction from 13 alfalfa samples. Pinitol was the most abundant inositol of leaves and stems (24.2–31.0 mg·g⁻¹ and 15.5–22.5 mg·g⁻¹, respectively) while seed extracts were rich in α-GOS, mainly in stachyose (48.8–84.7 mg·g⁻¹). In addition, inositols and α-GOS concentrations of lyophilized MAE extracts were stable for up to 26 days at 50 °C. These findings demonstrate that alfalfa is a valuable source of bioactive carbohydrates and MAE a promising alternative technique to obtain functional extracts. Full article

The interest for naturally-occurring oligosaccharides from plant origin having prebiotic properties is growing, with special focus being paid to supplemented products for infants. Currently, non-fructosylated α-galactooligosaccharides (α-GOS) from peas have peaked interest as a result of their prebiotic activity in adults and their mitigated side-effects on gas production from colonic bacterial fermentation. In this study, commercially available non-fructosylated α-GOS from peas and β-galactooligosaccharides (β-GOS) derived from lactose were fermented using fecal slurries from children aged 11 to 24 months old during 6 and 24 h. The modulatory effect of both GOS on different bacterial groups and bifidobacteria species was assessed; non-fructosylated α-GOS consumption was monitored throughout the fermentation process and the amounts of lactic acid and short-chain fatty acids (SCFA) generated were analyzed. Non-fructosylated α-GOS, composed mainly of manninotriose and verbascotetraose and small amounts of melibiose, were fully metabolized and presented remarkable bifidogenic activity, similar to that obtained with β-GOS. Furthermore, non-fructosylated α-GOS selectively caused an increase on the population of Bifidobacterium longum subsp. longum and Bifidobacterium catenulatum/pseudo-catenulatum. In conclusion, non-fructosylated α-GOS could be used as potential ingredient in infant formula supplemented with prebiotic oligosaccharides. Full article

This study investigated the suppression of photoaging by galacto-oligosaccharide (GOS) ingestion following exposure to ultraviolet (UV) radiation. To investigate its photoprotective effects, GOS along with collagen tripeptide (CTP) as a positive control was orally administered to hairless mice under UVB exposure for 8 weeks. The water holding capacity, transepidermal water loss (TEWL), and wrinkle parameters were measured. Additionally, quantitative reverse-transcription polymerase chain reaction and Western blotting were used to determine mRNA expression and protein levels, respectively. The GOS or CTP orally-administered group showed a decreased water holding capacity and increased TEWL compared to those of the control group, which was exposed to UVB (CON) only. In addition, the wrinkle area and mean wrinkle length in the GOS and CTP groups significantly decreased. Skin aging-related genes, matrix metalloproteinase, had significantly different expression levels in the CTP and GOS groups. Additionally, the tissue inhibitor of metalloproteinases and collagen type I gene expression in the CTP and GOS groups significantly increased. Oral administration of GOS and CTP significantly lowered the tissue cytokine (interleukin-6 and -12, and tumor necrosis factor-α) levels. There was a significant difference in UVB-induced phosphorylation of JNK, p38, and ERK between the GOS group and the CON group. Our findings indicate that GOS intake can suppress skin damage caused by UV light and has a UV photoprotective effect. Full article