2′-Fucosyllactose Ameliorates Oxidative Stress Damage in d-Galactose-Induced Aging Mice by Regulating Gut Microbiota and AMPK/SIRT1/FOXO1 Pathway

The imbalance of reactive oxygen species is the main cause in aging, accompanied by oxidative stress. As the most abundant in human milk oligosaccharides (HMOs), 2′-Fucosyllactose (2′-FL) has been confirmed to have great properties in immunity regulation and anti-inflammatory. The research on 2′-FL is focused on infants currently, while there is no related report of 2′-FL for the elderly. A d-galactose-induced accelerated aging model was established to explore the protective effect of 2′-FL on the intestines and brain in mice. In this study, 2′-FL significantly reduced oxidative stress damage and inflammation in the intestines of aging mice, potentially by regulating the sirtuin1 (SIRT1)-related and nuclear factor E2-related factor 2 (Nrf2) pathways. In addition, 2′-FL significantly improved the gut mucosal barrier function and increased the content of short-chain fatty acids (SCFAs) in the intestine. The gut microbiota analysis indicated that 2′-FL mainly increased the abundance of probiotics like Akkermansia in aging mice. Moreover, 2′-FL significantly inhibited apoptosis in the brains of aging mice, also increasing the expression of SIRT1. These findings provided a basis for learning the benefits of 2′-FL in the aging process.

The Role of Dietary and Microbial Fatty Acids in the Control of Inflammation in Neonatal Piglets

Excessive inflammation and a reduced gut mucosal barrier are major causes for gut dysfunction in piglets. The fatty acid (FA) composition of the membrane lipids is crucial for mediating inflammatory signalling and is largely determined by their dietary intake. Porcine colostrum and milk are the major sources of fat in neonatal piglets. Both are rich in fat, demonstrating the dependence of the young metabolism from fat and providing the young organism with the optimum profile of lipids for growth and development. The manipulation of sow’s dietary polyunsaturated FA (PUFA) intake has been shown to be an efficient strategy to increase the transfer of specific FAs to the piglet for incorporation in enteric tissues and cell membranes. n-3 PUFAs, especially seems to be beneficial for the immune response and gut epithelial barrier function, supporting the piglet’s enteric defences in situations of increased stress such as weaning. Little is known about microbial lipid mediators and their role in gut barrier function and inhibition of inflammation in neonatal piglets. The present review summarizes the current knowledge of lipid nutrition in new-born piglets, comparing the FA ingestion from milk and plant-based lipid sources and touching the areas of host lipid signalling, inflammatory signalling and microbially derived FAs.

Effects of enteral glutamine supplementation on intestinal permeability in acute pancreatitis: A literature review

Background. Glutamine has been shown to improve the gut mucosal barrier. However, the evidence for benefit of enteral glutamine on intestinal permeability in acute pancreatitis (AP) is limited. Objective. To identify the effect of enteral glutamine supplementation on intestinal permeability in patients with AP. Method. A systematic search was conducted by extracting evidence from published studies on enteral glutamine supplementation in three databases (PubMed, Cochrane Central Register of Controlled Trials, and SciElo) relevant to AP from 1 January 2010 till 31 December 2020. Outcomes assessed were intestinal permeability, infectious complication, hospital length of stay, and mortality rate. Results. A total of 6 studies found by search, in which 2 human RCTs with 7 days duration of intervention with 1b-1c quality based on Criteria by Center of Evidence-Based Medicine, University of Oxford. Both studies showed the benefit of early enteral glutamine supplementation on intestinal permeability in patients with AP. Conclusions. Enteral glutamine supplementation has been shown to improve the gut mucosal barrier in AP. Despite its significant improvement in intestinal permeability, glutamine supplementation did not display a consistently positive effect on clinical outcomes.

The gut microbiome: what the oncologist ought to know

The gut microbiome (GM) has been implicated in a vast number of human pathologies and has become a focus of oncology research over the past 5 years. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation and protection against pathogens. Strong evidence is emerging to support the effects of the GM on the development of some malignancies but also on responses to cancer therapies, most notably, immune checkpoint inhibition. Tools for manipulating the GM including dietary modification, probiotics and faecal microbiota transfer (FMT) are in development. Current understandings of the many complex interrelationships between the GM, cancer, the immune system, nutrition and medication are ultimately based on a combination of short‐term clinical trials and observational studies, paired with an ever-evolving understanding of cancer biology. The next generation of personalised cancer therapies focusses on molecular and phenotypic heterogeneity, tumour evolution and immune status; it is distinctly possible that the GM will become an increasingly central focus amongst them. The aim of this review is to provide clinicians with an overview of microbiome science and our current understanding of the role the GM plays in cancer.

Diet Rich in Simple Sugars Promotes Pro-Inflammatory Response via Gut Microbiota Alteration and TLR4 Signaling

Diet is a strong modifier of microbiome and mucosal microenvironment in the gut. Recently, components of western-type diets have been associated with metabolic and immune diseases. Here, we studied how high-sugar diet (HSD) consumption influences gut mucosal barrier and immune response under steady state conditions and in a mouse model of acute colitis. We found that HSD significantly increased gut permeability, spleen weight, and neutrophil levels in spleens of healthy mice. Subsequent dextran sodium sulfate administration led to severe colitis. In colon, HSD significantly promoted neutrophil infiltration and increased the levels of IL-6, IL-1β, and TNF-α. Moreover, HSD-fed mice had significantly higher abundance of pathobionts, such as Escherichia coli and Candida, in fecal samples. Although germ-free mice colonized with microbiota of conventionally reared mice that consumed different diets had equally severe colitis, mice colonized with HSD microbiota showed markedly increased infiltration of neutrophils to the gut. The induction of colitis in Toll-like receptor 4 (TLR4)-deficient HSD-fed mice led to significantly milder colitis than in wild-type mice. In conclusion, our results suggested a significant role of HSD in disruption of barrier integrity and balanced mucosal and systemic immune response. In addition, these processes seemed to be highly influenced by resident potentially pathogenic microbiota or metabolites via the TLR4 signaling pathway.

FAM3D is essential for colon homeostasis and host defense against inflammation associated carcinogenesis

The physiological homeostasis of gut mucosal barrier is maintained by both genetic and environmental factors and its impairment leads to pathogenesis such as inflammatory bowel disease. A cytokine like molecule, FAM3D (mouse Fam3D), is highly expressed in mouse gastrointestinal tract. Here, we demonstrate that deficiency in Fam3D is associated with impaired integrity of colonic mucosa, increased epithelial hyper-proliferation, reduced anti-microbial peptide production and increased sensitivity to chemically induced colitis associated with high incidence of cancer. Pretreatment of Fam3D−/− mice with antibiotics significantly reduces the severity of chemically induced colitis and wild type (WT) mice co-housed with Fam3D−/− mice phenocopy Fam3D-deficiency showing increased sensitivity to colitis and skewed composition of fecal microbiota. An initial equilibrium of microbiota in cohoused WT and Fam3D−/− mice is followed by an increasing divergence of the bacterial composition after separation. These results demonstrate the essential role of Fam3D in colon homeostasis, protection against inflammation associated cancer and normal microbiota composition.

A story of liver and gut microbes: how does the intestinal flora affect liver disease? A review of the literature

Each individual is endowed with a unique gut microbiota (GM) footprint that mediates numerous host-related physiological functions, such as nutrient metabolism, maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. Because of increased scientific interest in the GM, its central role in the pathophysiology of many intestinal and extraintestinal conditions has been recognized. Given the close relationship between the gastrointestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. In this review we introduce to neophytes the vast world of gut microbes, including prevalent bacterial distribution in healthy individuals, how the microbiota is commonly analyzed, and the current knowledge of the role of GM in liver disease pathophysiology. Also, we highlight the potentials and downsides of GM-based therapy.

Alterations of the Predominant Fecal Microbiota and Disruption of the Gut Mucosal Barrier in Patients with Early-Stage Colorectal Cancer

Growing evidence indicated that the gut microbiota was the intrinsic and essential component of the cancer microenvironment, which played vital roles in the development and progression of colorectal cancer (CRC). In our present study, we investigated the alterations of fecal abundant microbiota with real-time quantitative PCR and the changes of indicators of gut mucosal barrier from 53 early-stage CRC patients and 45 matched healthy controls. We found that the traditional beneficial bacteria such as Lactobacillus and Bifidobacterium decreased significantly and the carcinogenic bacteria such as Enterobacteriaceae and Fusobacterium nucleatum were significantly increased in CRC patients. We also found gut mucosal barrier dysfunction in CRC patients with increased levels of endotoxin (LPS), D-lactate, and diamine oxidase (DAO). With Pearson’s correlation analysis, D-lactate, LPS, and DAO were correlated negatively with Lactobacillus and Bifidobacterium and positively with Enterobacteriaceae and F. nucleatum. Our present study found dysbiosis of the fecal microbiota and dysfunction of the gut mucosal barrier in patients with early-stage CRC, which implicated that fecal abundant bacteria and gut mucosal barrier indicators could be used as targets to monitor the development and progression of CRC in a noninvasive and dynamic manner.