Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is one of the main types of intestinal inflammatory diseases with intestine mucosal immune disorder. Intestine mucosal immune system plays a remarkable and important role in the etiology and pathogenesis of IBD. Therefore, understanding the intestine mucosal immune mechanism is a key step to develop therapeutic interventions for IBD. Intestine mucosal immune system and IBD are influenced by various factors, such as inflammation, gut permeability, gut microbiota, and nutrients. Among these factors, emerging evidence show that nutrients play a key role in inflammation activation, integrity of intestinal barrier, and immune cell modulation. Lactoferrin (LF), an iron-binding glycoprotein belonging to transferrin family, is a dietary bioactive component abundantly found in mammalian milk. Notably, LF has been reported to perform diverse biological functions including antibacterial activity, anti-inflammatory activity, intestinal barrier protection, and immune cell modulation, and is involved in maintaining intestine mucosal immune homeostasis. The improved understanding of the properties of LF in intestine mucosal immune system and IBD will facilitate its application in nutrition, clinical medicine, and health. Herein, this review outlines the recent advancements on LF as a potential therapeutic intervention for IBD associated with intestine mucosal immune system dysfunction. We hope this review will provide a reference for future studies and lay a theoretical foundation for LF-based therapeutic interventions for IBD by understanding the particular effects of LF on intestine mucosal immune system.

Autophagy is a multi-step catabolic process that delivers cellular components to lysosomes for degradation and recycling. The dysregulation of this precisely controlled process disrupts cellular homeostasis and leads to many pathophysiological conditions. The mechanistic target of rapamycin (mTOR) is a central nutrient sensor that integrates growth signals with anabolism to fulfil biosynthetic and bioenergetic requirements. mTOR nucleates two distinct evolutionarily conserved complexes (mTORC1 and mTORC2). However, only mTORC1 is acutely inhibited by rapamycin. Consequently, mTORC1 is a well characterized regulator of autophagy. While less is known about mTORC2, the availability of acute small molecule inhibitors and multiple genetic models has led to increased understanding about the role of mTORC2 in autophagy. Emerging evidence suggests that the regulation of mTORC2 in autophagy is mainly through its downstream effector proteins, and is variable under different conditions and cellular contexts. Here, we review recent advances that describe a role for mTORC2 in this catabolic process, and propose that mTORC2 could be a potential clinical target for the treatment of autophagy-related diseases. Graphical

Neonicotinoids are a widely used class of pesticides. Co‐exposure to neonicotinoids and other classes of pesticides can exert potentiating or synergistic effects, and these mixtures have been detected in human bodily fluids. The present review summarizes studies into the effects of neonicotinoid‐containing pesticide mixtures on humans and other nontarget organisms. Exposure to these mixtures has been reported to result in reproductive and hormonal toxicity, genotoxicity, neurotoxicity, hepatotoxicity, and immunotoxicity in vertebrates. Mortality of pollinators and toxicity in other organisms has also been reported. The underlying mechanism of pesticide mixture toxicity may be associated with impairment of cytochrome 450 enzymes, which are involved in metabolizing pesticides. However, a comprehensive explanation of the adverse effects of neonicotinoid‐containing pesticide mixtures is still required so that effective prevention and control measures can be formulated. Environ Toxicol Chem 2020;00:1–10. © 2020 SETAC

Organophosphorus pesticides (OPs) remain one of the most commonly used pesticides, and their detection rates and residues in agricultural products, foods and environmental samples have been underestimated. Humans and environmental organisms are at high risk of exposure to OPs. Most OPs can be degraded and metabolized into dialkyl phosphates (DAPs) in organisms and the environment, and can be present in urine as biomarkers for exposure to OPs, of which diethyl phosphate (DEP) is a high-exposure metabolite. Epidemiological and cohort studies have found that DAPs are associated with endocrine hormone disorders, especially sex hormone disorders and thyroid hormone disorders, but there has been no direct causal evidence to support these findings. Our study explored the effects of chronic exposure to DEP on endocrine hormones and related metabolic indicators in adult male rats at actual doses that can be reached in the human body. The results showed that chronic exposure to DEP could cause thyroid-related hormone disorders in the serum of rats, causing symptoms of hyperthyroidism in rats, and could also lead to abnormal expression of thyroid hormone-related genes in the rat liver. However, DEP exposure did not seem to affect serum sex hormone levels, spermatogenesis or sperm quality in rats. The molecular interactions between DEP and thyroid hormone-related enzymes/proteins were investigated by molecular docking and molecular dynamics methods in silico. It was found that DEP could strongly interact with thyroid hormone biosynthesis, blood transport, receptor binding and metabolism-related enzymes/proteins, interfering with the production and signal regulation of thyroid hormones. In vivo and in silico experiments showed that DEP might be a potential thyroid hormone-disrupting chemical, and therefore, we need to be more cautious and rigorous regarding organophosphorus chemical exposure.

Probiotics have been reported to be associated with the alleviation of constipation. The aim of this study was to detect and determine the effect of Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) on the alleviation of constipation in BALB/c mice and humans, and to elucidate the mechanisms underlying its effect by measuring changes in the concentration of short-chain fatty acids and the composition of microbes in human faeces. BALB/c mice were given MN-Gup by gavage for 14 days. On the 8^th day of this treatment, constipation was induced by the application of diphenoxylate via gavage. The results showed that MN-Gup significantly decreased the first black stool defecation time, and significantly increased black faecal wet weight, black faecal number and the gastric-intestinal transit rate (P<0.05), thereby relieving constipation. In humans, a randomised, double-blind, placebo-controlled trial was performed to investigate the effect of MN-Gup in adults with functional constipation. After 4 weeks of intervention with placebo or MN-Gup yogurt, constipation-related symptoms (including defecation frequency, stool consistency, straining and incomplete feeling during defecation) in the constipated subjects were significantly improved in the two groups, but not different between the groups at the end of the intervention. The concentration of acetate increased significantly in the MN-Gup group compared to the placebo group and before ingestion. Significant changes in the composition of gut microbiota were found after intake of MN-Gup yogurt when compared to placebo. The relative abundances of acetate-producing Bifidobacterium, Ruminoccaceae_UCG-002 and Ruminoccaceae_UCG-005 were significantly increased after intake of MN-Gup yogurt. These results showed that MN-Gup could relieve constipation related to increased acetate-producing Bifidobacterium, Ruminoccaceae_UCG-002 and Ruminoccaceae_UCG-005.

Probiotics are widely known for their health benefits. Mitochondrial dysfunction is related to obesity. The aim of this study was to illuminate whether Bifidobacterium animalis subsp. lactis A6 (BAA6) could improve obesity due to increased mitochondrial biogenesis and function of adipose tissues. Four-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 17 weeks. For the final eight weeks, the HFD group was divided into three groups including HFD, HFD with BAA6 (HFD + BAA6 group), and HFD with Akkermansia muciniphila (AKK) (HFD + AKK group as positive control). The composition of the microbiota, serum lipopolysaccharides (LPS), and mitochondrial biosynthesis and function of epididymal adipose tissues were measured. Compared with the HFD group, body weight, relative fat weight, the relative abundance of Oscillibacter and Bilophila, and serum LPS were significantly decreased in the HFD + BAA6 and HFD + AKK groups (p < 0.05). Furthermore, the addition of BAA6 and AKK increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (by 21.53- and 18.51-fold), estrogen-related receptor α (ERRα) (by 2.83- and 1.24-fold), and uncoupling protein-1 (UCP-1) (by 1.51- and 0.60-fold) in epididymal adipose tissues. Our results suggest that BAA6 could improve obesity associated with promoting mitochondrial biogenesis and function of adipose tissues in mice.