Galactooligosaccharide or 2'-Fucosyllactose Modulates Gut Microbiota and Inhibits LPS/TLR4/NF-κB Signaling Pathway to Prevent DSS-Induced Colitis Aggravated by a High-Fructose Diet in Mice.

A high-fructose diet (HFrD) has been reported to exacerbate dextran sulfate sodium (DSS)-induced colitis. 2'-Fucosyllactose (FL) and galactooligosaccharide (GOS) have been shown, respectively, to have preventive and ameliorative effects on colitis, while limited research has explored whether GOS and FL may be equally protective or preventive in mice with HFrD. Here, we evaluated the protective effects of FL and GOS on colitis exacerbated by feeding HFrD and explored the underlying mechanisms. DSS-induced colitis was studied in four randomized C57BL/6J male mice (n = 8 mice/group). Among them, three groups were fed with HFrD, and two received either GOS or FL treatment, respectively. Gut microbial composition was analyzed by 16S rDNA gene sequencing. Intestinal barrier integrity and inflammatory pathway expression were measured using qPCR, immunofluorescence, and Western blot methods. Compared to the HFrD group, GOS or FL treatment increased the α-diversity of the gut microbiota, reduced the relative abundance of Akkermansia, and increased the content of short-chain fatty acids (SCFAs), respectively. Compared with the HFrD group, GOS or FL treatment improved the loss of goblet cells and the reduction of tight junction protein expression, thereby improving intestinal barrier integrity. Also, GOS or FL inhibited the LPS/TLR4/NF-κB signaling pathway and oxidative stress to suppress the inflammatory cascade compared with the HFrD group. These findings suggest that GOS or FL intake can alleviate HFrD-exacerbated colitis, with no significant difference observed between GOS and FL treatments.

Galactooligosaccharides ameliorate dietary advanced glycation end product-induced intestinal barrier damage in C57BL/6 mice by modulation of the intestinal microbiome.

Advanced glycation end products (AGEs) are increasingly recognized as potentially pathogenic components of processed foods, and long-term consumption of dietary AGEs triggers disruption of the intestinal barrier integrity and increases the risk of chronic diseases. Galactooligosaccharides (GOS) as prebiotics can modulate the intestinal microbiota and improve the intestinal barrier integrity. In this study, we aimed to investigate whether GOS could ameliorate the intestinal barrier damage induced by AGEs. The results showed an increased number of goblet cells (AGEs vs. H-GOS, 133.4 vs. 174.7, p < 0.05) and neutral mucin area (PAS positive area, 7.29% vs. 10.05%, p < 0.05). Upregulated expressions of occludin and claudin-1 and improved intestinal barrier integrity were observed in the H-GOS group. Using 16S rRNA sequencing analysis, we found that GOS significantly reduced the high enrichment of Akkermansia (16.95% vs. 1.29%, p < 0.05) induced by dietary AGEs while increasing the content of short-chain fatty acids. Fecal microbiota transplantation (FMT) showed that AGE-induced damage to the intestinal mucus barrier was reversed in the H-GOS transplanted group. Collectively, GOS ameliorated dietary AGE-induced intestinal barrier damage by reversing the dysregulated state of the intestinal microbiota. Our study lays the foundation for further research on dietary guidelines for populations with high AGE diets.

Comparison of tissue distribution of free and protein bound Nɛ-carboxymethyllysine after long-term oral administration to mice.

Nɛ-Carboxymethyl-lysine (CML) is a primary advanced glycation end product that exists in the body and food as free and bound forms with different bioavailability and physiological effects. To compare the uptake, tissue distribution, and fecal excretion of dietary free and bound CML, free or bound CML were administered to healthy mice at 10 mg CML kg-1 body weight per day for 12 weeks. The results demonstrated that free CML was significantly absorbed in serum and accumulated in the colon, ileum, lung, kidneys, heart, spleen, brain, and liver after intake of free and bound CML, whereas no statistical increase was found in the accumulation of bound CML in the serum, lung, spleen, kidneys, and liver. The colon was the main tissue for the accumulation of free and total CML. Moreover, the accumulation of free CML in tissues and organs was significantly correlated with free CML levels in serum. In conclusion, consumption of bound CML caused a higher uptake, accumulation, and fecal excretion of CML in the body than intake of free CML.

Hypoglycemic Effects of Lycium barbarum Polysaccharide in Type 2 Diabetes Mellitus Mice via Modulating Gut Microbiota.

This study aims to explore the molecular mechanisms of Lycium barbarum polysaccharide (LBP) in alleviating type 2 diabetes through intestinal flora modulation. A high-fat diet (HFD) combined with streptozotocin (STZ) was applied to create a diabetic model. The results indicated that LBP effectively alleviated the symptoms of hyperglycemia, hyperlipidemia, and insulin resistance in diabetic mice. A high dosage of LBP exerted better hypoglycemic effects than low and medium dosages. In diabetic mice, LBP significantly boosted the activities of CAT, SOD, and GSH-Px and reduced inflammation. The analysis of 16S rDNA disclosed that LBP notably improved the composition of intestinal flora, increasing the relative abundance of Bacteroides, Ruminococcaceae_UCG-014, Intestinimonas, Mucispirillum, Ruminococcaceae_UCG-009 and decreasing the relative abundance of Allobaculum, Dubosiella, Romboutsia. LBP significantly improved the production of short-chain fatty acids (SCFAs) in diabetic mice, which corresponded to the increase in the beneficial genus. According to Spearman's correlation analysis, Cetobacterium, Streptococcus, Ralstonia. Cetobacterium, Ruminiclostridium, and Bifidobacterium correlated positively with insulin, whereas Cetobacterium, Millionella, Clostridium_sensu_stricto_1, Streptococcus, and Ruminococcaceae_UCG_009 correlated negatively with HOMA-IR, HDL-C, ALT, AST, TC, and lipopolysaccharide (LPS). These findings suggested that the mentioned genus may be beneficial to diabetic mice's hypoglycemia and hypolipidemia. The up-regulation of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and insulin were remarkably reversed by LBP in diabetic mice. The real-time PCR (RT-PCR) analysis illustrated that LBP distinctly regulated the glucose metabolism of diabetic mice by activating the IRS/PI3K/Akt signal pathway. These results indicated that LBP effectively alleviated the hyperglycemia and hyperlipidemia of diabetic mice by modulating intestinal flora.

Ovomucin Ameliorates Intestinal Barrier and Intestinal Bacteria to Attenuate DSS-Induced Colitis in Mice.

Egg white ovomucin (OVM) is homologically related to MUC2, the key component of colonic mucous layer. This study investigated the effects of orally administered OVM from egg white on the colonic mucosal barrier and the development of colitis using a colitis C57BL/6J mice model. The results showed that daily supplementation of 125 and 250 mg/kg BW of OVM partially relieved the villous destruction and loss of intestinal barrier integrity, and hence decreased the epithelial barrier permeability. The supplementation also reduced the secretion of proinflammatory cytokines TNF-α and IL-6. Besides, OVM administration significantly increased the relative abundance of intestinal beneficial bacteria including Lactobacilli, Faecalibaculum, Ruminococcus, etc. and further upregulated the production of bacterial metabolites such as short-chain fatty acids (SCFAs), which is a direct source of energy for the proliferation of epithelia and goblet cells. In conclusion, OVM from egg white ameliorates colitis by enhancing the intestinal barrier function and abundance of intestinal bacteria, thereby increasing the number of SCFAs.

Potential role of ovomucin and its peptides in modulation of intestinal health: A review.

Intestinal dysfunction, which may cause a series of metabolic diseases, has become a worldwide health problem. In the past few years, studies have shown that consumption of poultry eggs has the potential to prevent a variety of metabolic diseases, and increasing attention has been directed to the bioactive proteins and their peptides in poultry eggs. This review mainly focused on the biological activities of an important egg-derived protein named ovomucin. Ovomucin and its derivatives have good anti-inflammatory, antioxidant, immunity-regulating and other biological functions. These activities may affect the physical, biological and immune barriers associated with intestinal health. This paper reviewed the structure and the structure-activity relationship of ovomucin，the potential role of ovomucin and its derivatives in modulation of intestinal health are also summarized. Finally, the potential applications of ovomucin and its peptides as functional food components to prevent and assist in the pretreatment of intestinal health problems are prospected.

Effectively preparing soluble ovomucin with high antiviral activity from egg white.

Ovomucin has a great potential because of its numerous bioactivities, which makes it an attractive molecule for industrials. However, to isolate soluble ovomucin without degradation and contamination remains a challenge. In this study, ovomucin of high purity (99.13%) was obtained in good yield (3.02 g kg-1 fresh egg white) via an improved two-step precipitation followed by gel filtration chromatography. The IC50 of the preparation for three representative new disease virus strains named LaSota, Mukteswar and V-4 is 1.99, 4.95 and 5.78 × 10-3 g L-1, respectively. Produced ovomucin showed limited reduction in the hemagglutination inhibition activity against all of the virus strains during the purification. Infrared spectroscopy of the ovomucin preparation indicated extensive glycosylation and sulfation. Amino acid analysis found that it was rich in alanine, glutamic acid, threonine and valine residues, which is typical in mucins. The improved process developed in this study is an alternative approach to obtain pure ovomucin with elevated antiviral activity and purity, which may significantly push forward the further research on bioactivities of ovomucin.