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This study aimed to evaluate the anti-colitis potential of platinum nanoparticles (PtNPs). 5-, 30- and 70-nm PtNPs were administered to C57BL/6 mice once daily by intragastric gavage for 8 d during and after 5-d dextran sodium sulfate treatment. According to body weight change, stool blood and consistency, and colon length and histopathology, PtNPs size-dependently alleviated DSS-induced murine colitis. PtNPs enhanced gut-barrier function by upregulating the colonic expressions of heat-shock protein 25 and tight junction proteins. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of white blood cells, PtNPs attenuated colonic and systemic inflammation. By suppressing lipopolysaccharide-triggered production of proinflammatory mediators, including nitric oxide, tumor necrosis factor-α and interleukin-6, PtNPs exerted direct anti-inflammatory activities in RAW264.7 macrophages through a mechanism involving intracellular reactive oxygen species scavenging and Toll-like receptor 4/NF-κB signaling suppression. High-throughput 16S rRNA sequencing of fecal samples unveiled that PtNPs induced gut dysbiosis by unfavorably altering α-diversity, Firmicutes/Bacteroidetes ratio, and richness of certain specific bacteria. PtNPs are a promising anti-colitis agent, but may negatively impact gut-microbiota.

A major challenge in affluent societies is the increase in disorders related to gut and metabolic health. Chronic over nutrition by unhealthy foods high in energy, fat, and sugar, and low in dietary fibre is a key environmental factor responsible for this development, which may cause local and systemic inflammation. A low intake of dietary fibre is a limiting factor for maintaining a viable and diverse microbiota and production of short-chain fatty acids in the gut. A suppressed production of butyrate is crucial, as this short-chain fatty acid (SCFA) can play a key role not only in colonic health and function but also at the systemic level. At both sites, the mode of action is through mediation of signalling pathways involving nuclear NF-κB and inhibition of histone deacetylase. The intake and composition of dietary fibre modulate production of butyrate in the large intestine. While butyrate production is easily adjustable it is more variable how it influences gut barrier function and inflammatory markers in the gut and periphery. The effect of butyrate seems generally to be more consistent and positive on inflammatory markers related to the gut than on inflammatory markers in the peripheral tissue. This discrepancy may be explained by differences in butyrate concentrations in the gut compared with the much lower concentration at more remote sites.

Cyclophosphamide (CTX), used in cancer chemotherapy, a high dose of which would cause immunosuppressive effect and intestinal mucosa damage. American ginseng ( Panax quinquefolius L.) has a long history of functional food use for immunological disorder, colitis, cancer, and so on. This study aimed to illustrate the underlying mechanism of American ginseng’s immunomodulatory effect in CTX-induced mice. In this study, all groups of American ginseng (American ginseng polysaccharide [AGP], American ginseng ginsenoside [AGG], co-treated with American ginseng polysaccharide and ginsenoside [AGP_AGG]) have relieve the immune disorder by reversing the lymphocyte subsets ratio in spleen and peripheral blood, as well as stimulating CD4 + T cells and IgA-secreting cells in small intestine. These three treatment groups, especially AGP_AGG co-treated group recovered the intestine morphology that up-regulated villus height (VH)/crypt depth (CD) ratio, areas of mucins expression, quantity of goblet cells, and expression of tight junction proteins (ZO-1, occludin). Importantly, the microbiome-metabolomics analysis was applied in this study to illustrate the possible immuno-modulating mechanism. The synergistic effect of polysaccharides and ginsenosides (AGP_AGG group) restored the gut microbiota composition and increased various beneficial mucosa-associated bacterial taxa Clostridiales, Bifidobacterium, and Lachnospiraceae, while decreased harmful bacteria Escherichia-Shigella and Peptococcaceae. Also, AGP_AGG group altered various fecal metabolites such as uric acid, xanthurenic acid, acylcarnitine, 9,10-DHOME, 13-HDoHE, LysoPE15:0, LysoPC 16:0, LysoPI 18:0, and so on, that associated with immunometabolism or protective effect of gut barrier. These results suggest AG, particularly co-treated of polysaccharide and ginsenoside may be used as immunostimulants targeting microbiome-metabolomics axis to prevent CTX-induced side effects in cancer patients.

Human milk oligosaccharides (HMOs) shape the gut microbiota in infants by selectively stimulating the growth of bifidobacteria. Here, we investigated the impact of HMOs on adult gut microbiota and gut barrier function using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), Caco2 cell lines, and human intestinal gut organoid-on-chips. We showed that fermentation of 2’-O-fucosyllactose (2’FL), lacto-N-neotetraose (LNnT), and combinations thereof (MIX) led to an increase of bifidobacteria, accompanied by an increase of short chain fatty acid (SCFA), in particular butyrate with 2’FL. A significant reduction in paracellular permeability of FITC-dextran probe was observed using Caco2 cell monolayers with fermented 2’FL and MIX, which was accompanied by an increase in claudin-8 gene expression as shown by qPCR, and a reduction in IL-6 as determined by multiplex ELISA. Using gut-on-chips generated from human organoids derived from proximal, transverse, and distal colon biopsies (Colon Intestine-Chips), we showed that claudin-5 was significantly upregulated across all three gut-on-chips following treatment with fermented 2’FL under microfluidic conditions. Taken together, these data show that, in addition to their bifidogenic activity, HMOs have the capacity to modulate immune function and the gut barrier, supporting the potential of HMOs to provide health benefits in adults.

5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella , which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter , which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.

Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco‐2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK‐UCP 2 pathway via binding to the integrin αVβ5 receptor. Inhibition of integrin αVβ5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin αVβ5‐AMPK‐UCP 2 pathway.

Background One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed. Results IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 ( P  < 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 ( P  = 0.050), IVS-1 + GOS ( P  = 0.022), and GOS ( P  = 0.010), while sucralose excretion was reduced with BB-12 ( P  = 0.002) and GOS ( P  = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed. Conclusion This study demonstrated that “autochthony” of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut.

This study was aimed at determining potential effects of apple-derived pectin on weight gain, gut microbiota, gut barrier and metabolic endotoxemia in rat models of diet-induced obesity. The rats received a standard diet (control; Chow group; n = 8) or a high-fat diet (HFD; n = 32) for eight weeks to induce obesity. The top 50th percentile of weight-gainers were selected as diet induced obese rats. Thereafter, the Chow group continued on chow, and the diet induced obese rats were randomly divided into two groups and received HFD (HF group; n = 8) or pectin-supplemented HFD (HF-P group; n = 8) for six weeks. Compared to the HF group, the HF-P group showed attenuated weight gain (207.38 ± 7.96 g vs. 283.63 ± 10.17 g, p < 0.01) and serum total cholesterol level (1.46 ± 0.13 mmol/L vs. 2.06 ± 0.26 mmol/L, p < 0.01). Compared to the Chow group, the HF group showed a decrease in Bacteroidetes phylum and an increase in Firmicutes phylum, as well as subordinate categories (p < 0.01). These changes were restored to the normal levels in the HF-P group. Furthermore, compared to the HF group, the HF-P group displayed improved intestinal alkaline phosphatase (0.57 ± 0.20 vs. 0.30 ± 0.19, p < 0.05) and claudin 1 (0.76 ± 0.14 vs. 0.55 ± 0.18, p < 0.05) expression, and decreased Toll-like receptor 4 expression in ileal tissue (0.76 ± 0.58 vs. 2.04 ± 0.89, p < 0.01). The HF-P group also showed decreased inflammation (TNFα: 316.13 ± 7.62 EU/mL vs. 355.59 ± 8.10 EU/mL, p < 0.01; IL-6: 51.78 ± 2.35 EU/mL vs. 58.98 ± 2.59 EU/mL, p < 0.01) and metabolic endotoxemia (2.83 ± 0.42 EU/mL vs. 0.68 ± 0.14 EU/mL, p < 0.01). These results suggest that apple-derived pectin could modulate gut microbiota, attenuate metabolic endotoxemia and inflammation, and consequently suppress weight gain and fat accumulation in diet induced obese rats.

Background/Objectives: Chronic inflammation and Western-style diets elevate colorectal cancer (CRC) risk, particularly in individuals with colitis, a feature of inflammatory bowel disease (IBD). Diets rich in polyphenol-containing functional foods, such as cocoa, may reduce gut inflammation and modulate the gut microbiome. This study investigated the impact of cocoa polyphenol (CP) supplementation on inflammation and microbiome composition in mice with colitis, fed either a healthy or Western diet, before, during, and after the onset of disease. We hypothesized that CPs would attenuate inflammation and promote distinct shifts in the microbiome, especially in the context of a Western diet. Methods: A 2 × 2 factorial design tested the effects of the basal diet (AIN93G vs. total Western diet [TWD]) and CP supplementation (2.6% w/w CocoaVia™ Cardio Health Powder). Inflammation was induced using the AOM/DSS model of colitis. Results: CP supplementation did not reduce the severity of colitis, as measured by disease activity index or histopathology. CPs did not alter gene expression in healthy tissue or suppress the colitis-associated pro-inflammatory transcriptional profile in either of the two diet groups. However, fecal microbiome composition shifted significantly with CPs before colitis induction, with persistent effects on several rare taxa during colitis and recovery. Conclusions: CP supplementation did not mitigate inflammation or mucosal injury at the tissue level, nor did it affect the expression of immune-related genes. While CPs altered microbiome composition, most notably in healthy mice before colitis, these shifts did not correspond to changes in inflammatory signaling. Basal diet remained the primary determinant of inflammation, mucosal damage, and colitis severity in this model.

Obesity in the pediatric population has become a public health problem with an increasing prevalence in recent years. The gut microbiota and its metabolites, especially short-chain fatty acids (SCFAs), play vital roles in the development of pediatric obesity. This manuscript aims to highlight the link between the gut microbiota and obesity by examining microbial imbalances, such as altered Firmicutes/Bacteroidetes ratios and altered SCFA production, especially butyrate, propionate, and acetate. Advances in genomic technologies, such as 16S rRNA sequencing, have enabled personalized treatments and detailed profiling of microbial diversity. This review includes not only preclinical studies but also clinical trials of interventions, such as probiotics, synbiotics, prebiotics, and butyrate supplements. These may modify the microbiota and SCFA levels to reduce obesity and related conditions, such as metabolic syndrome and precocious puberty. Future research should focus on using advanced genomic sequencing techniques to develop new therapeutic strategies, as well as on creating a complex predictive algorithm for assessing metabolic risk in pediatric patients with obesity, an innovation that can be extended to other metabolic conditions.