Effects of potassium sorbate on systemic inflammation and gut microbiota in normal mice: A comparison of continuous intake and washout period.

Potassium sorbate (PS) is a widely used food preservative in the field of food industry. However, the effects of continuous intake and washout period of PS on host health are still unclear. In this study, to investigate long-term effect and after-effect of different concentrations and time points of PS, healthy mice were orally exposed to 150 mg/kg, 500 mg/kg and 1000 mg/kg of PS for 10 weeks, and washout treatment for another 5 weeks, respectively. The results indicated that PS intake for 10 weeks had no obvious effects on organs and adipose tissue, nor did it noteworthily interfere with glucolipid metabolism in the serum. However, it caused inflammatory cell infiltration in the liver, increased serum interleukin (IL)-1ß level, changed abundances of gut microbiota but failed to promote the production of short chain fatty acids in the gut. After washout period for 5 weeks, liver inflammation and IL-1ß level were decreased, and gut environment developed towards a healthier condition. Specifically, PS washout significantly increased abundance of Lachnospiraceae_NK4A136_group and the production of isobutyric acid. This study confirmed washout period eliminated negative effects from continuous intake of PS, which provided positive evidence for its safety.

The Effect of Sodium Benzoate on Host Health: Insight into Physiological Indexes and Gut Microbiota.

Sodium benzoate (SB) is a common food preservative widely used in the food industry. However, the effects of SB intake on host health at different stages were still unclear. Hence, we investigated the impact of SB with three concentrations (150 mg/kg, 500 mg/kg and 1000 mg/kg) and at three stages (intake for 5-weeks, intake for 10-weeks and removal for 5 weeks) on host health in normal mice. The results showed that SB intake for 5 weeks slightly changed gut microbiota composition, but it significantly increased TG (only 150 mg/kg and 1000 mg/kg) and blood glucose levels (only 500 mg/kg) and promoted the secretion of interleukin (IL)-1ß and IL-6 (p < 0.01). However, SB intake for 10 weeks mostly maintained normal glucolipid metabolism; although, IL-1ß (p < 0.01) and IL-6 (p < 0.05) levels were also significantly increased and positively regulated the gut microbiota by significantly increasing the relative abundance of Lactobacillus and significantly decreasing the relative abundance of Ileibacterium. Meanwhile, the safety of SB for host metabolism and gut microbiota was also confirmed via a fecal microbiota transplantation experiment. In addition, we found that SB removal after 10 weeks of intake significantly increased the levels of blood glucose, insulin and HOMA-IR index, which might be attributed to gut microbiota dysbiosis. Mechanistically, these positive effects and negative effects had no close relationship with the concentration of short-chain fatty acids in the gut, which might be associated with metabolites of SB or special bacterial strains. In short, this work provided positive evidence for the safety of SB consumption within the recommended range.

Evaluation of dynamic effects of dietary medium-chain monoglycerides on performance, intestinal development and gut microbiota of broilers in large-scale production.

Medium-chain monoglycerides (MG) have been reported to affect the productive performance, gut microbiota and health of broiler chickens reared in ideal experimental conditions at home and abroad. However, the effects of MG on performance, intestinal development and gut microbiota of chickens in large-scale farms during different feed stages remain unknown. The present study was conducted on a modern farm with a total of 12,000 yellow feathered broiler chicks that were randomly allotted to 2 groups (1000 chicks/replicate, 6 replicates/group) for a 70-day trial. The control group (CON group) received a basal diet, and the treated group (MG group) was fed a basal diet containing 300 mg/kg mixed MG. The results revealed that dietary MG significantly (P < 0.05) increased the body weight and average feed intake, but notably reduced the feed conversion and mortality of chickens in large-scale production during the starter phase. The villus height of the duodenum in the MG group at 1, 2 and 7 wk of age increased notably, and the villus height to crypt depth ratio at 1, 2, 5 and 10 wk of age was improved. Dietary MG decreased the serum insulin content of chickens at 5, 7 and 10 wk of age, and decreased the serum lipopolysaccharide at 3 and 7 wk of age. The triglyceride level of chickens at 3, 5 and 10 wk of age and the low-density lipoprotein cholesterol level of chickens at 7 and 10 wk of age in the MG group decreased notably, while the high-density lipoprotein cholesterol increased significantly. Moreover, MG supplementation selectively increased the relative abundance of genus Bacteroides (family Bacteroidaceae) and Lachnospiraceae_NK4A136_group, but decreased the content of genus Rikenellaceae_RC9_gut_group, Collinsella and family Barnesiellaceae in the cecum of chickens at 3, 7 and 10 wk of age. Conclusively, these findings showed that dietary MG notably enhanced chicken performance, health and feed nutrient utilization at early ages by regulating gut microbiota, intestinal development and serum biochemical indices.

Integrated Serum Metabolome and Gut Microbiome to Decipher Chicken Amino Acid Improvements Induced by Medium-Chain Monoglycerides.

Chicken muscle yield and amino acid composition improvements with medium-chain monoglyceride (MG) supplementation were reported by previous studies, but the underlying mechanism was uncertain. This study aimed to decipher chicken amino acid improvements induced by medium-chain monoglycerides in the views of metabolomics, gene expression, and the gut microbiome. Newly hatched chicks (12,000 chicks) were weighed and randomly divided into two flocks, each with six replicates (1000 chicks per replicate), and fed a basal diet (the control group, CON) or a basal diet enriched with 300 mg/kg MG (the treated group, MG). Results demonstrated that MGs significantly increased the chicken flavor and essential and total amino acids. The serum amino acids and derivatives (betaine, l-leucine, l-glutamine, 1-methylhistide), as well as amino acid metabolism pathways in chickens, were enhanced by MG supplementation. Gene expression analysis exhibited that dietary MGs could improve muscle protein synthesis and cell growth via the mTOR/S6K1 pathway. Dietary MGs enhanced the cecal amino acid metabolism by selectively increasing the proportion of genera Lachnospiraceae_NK4A136_group and Bacteroides. Conclusively, the present study demonstrated that dietary MGs improved chicken amino acid composition via increasing both gut amino acid utilization and muscle amino acid deposition.

Enhancement in the metabolic profile of sea buckthorn juice via fermentation for its better efficacy on attenuating diet-induced metabolic syndrome by targeting gut microbiota.

To enhance physiological activity and probiotic availability of sea buckthorn juice, sea buckthorn juice pulp (BHJ) went through fermentation to the fermented (FHJ). In vitro, FHJ displayed better antioxidant and antidiabetic capacities. To further study effects of FHJ on diet-induced metabolic syndrome (MS) and possible mechanisms in vivo, C57BL/6 mice were fed on BHJ and FHJ under high fat diet (HFD). FHJ, rather BHJ, displayed better performance on ameliorating hyperlipidemia, insulin resistance, and oxidative stress in MS. Mechanistically, FHJ intervention significantly reversed the microorganism dysbiosis by restoring the microbial diversity, and modulating obesogenic bacteria abundance, like Oscillospira. Furthermore, fermentation altered FHJ's metabolomics, especially flavonoids, contributing to interactions between FHJ and probiotics, like Akkermansia and Lachnospiraceae. Furthermore, short-chain fatty acids, related to ameliorations of MS, were increased by FHJ. This study demonstrated that interactions between metabolomic alterations in FHJ and microorganisms were vital to attenuate MS.

Novel Gut Microbiota Patterns Involved in the Attenuation of Dextran Sodium Sulfate-Induced Mouse Colitis Mediated by Glycerol Monolaurate via Inducing Anti-inflammatory Responses.

Inflammatory bowel disease (IBD) is a type of immune-mediated chronic and relapsing inflammatory gastrointestinal symptoms. IBD cannot be completely cured because of the complex pathogenesis. Glycerol monolaurate (GML), naturally found in breast milk and coconut oil, has excellent antimicrobial, anti-inflammatory, and immunoregulatory functions. Here, the protective effect of GML on dextran sodium sulfate (DSS)-induced mouse colitis and the underlying gut microbiota-dependent mechanism were assessed in C57BL/6 mice pretreated or cotreated with GML and in antibiotic-treated mice transplanted with GML-modulated microbiota. Results showed that GML pretreatment has an advantage over GML cotreatment in alleviating weight loss and reducing disease activity index (DAI), colonic histological scores, and proinflammatory responses. Moreover, the amounts of Lactobacillus and Bifidobacterium and fecal propionic acid and butyric acid were elevated only in mice pretreated with GML upon DSS induction. Of note, fecal microbiota transplantation (FMT) from GML-pretreated mice achieved faster and more significant remission of DSS-induced colitis, manifested as reduced DAI, longer colon, decreased histological scores, and enhanced colonic Foxp3+ regulatory T cells (Tregs) and ratio of serum anti-inflammatory/proinflammatory cytokines, as well as the reconstruction of microbial communities, including elevated Helicobacter ganmani and decreased pathogenic microbes. In conclusion, GML-mediated enhancement of Bifidobacterium and fecal short-chain fatty acids (SCFAs) could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Importantly, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved. IMPORTANCE The gut microbiota, which can be highly and dynamically affected by dietary components, is closely related to IBD pathogenesis. Here, we demonstrated that food-grade glycerol monolaurate (GML)-mediated enhancement of Bifidobacterium and fecal SCFAs could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Collectively, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved, which further provided a perspective to identify specific microbial members and those responsible for the anticolitis effect, such as Bifidobacterium and Helicobacter.

Mass spectrometry-based metabolomics to reveal chicken meat improvements by medium-chain monoglycerides supplementation: Taste, fresh meat quality, and composition.

This study was conducted to reveal the differences of chicken fresh meat quality, composition and taste induced by medium-chain monoglycerides (MG) supplementation. Results demonstrated that both chicken broth and meat taste were improved by MG supplementation. The up-regulated l-carnosine, sarcosine, uridine and nicotinamide in the chicken broth of the MG group contributed to the umami and meaty taste. Dietary MG increased the total superoxide dismutase activity and amino acid content in the muscle of chicken breast and reduced the malondialdehyde content and drip loss. Moreover, meat metabolome revealed that creatine, betaine, l-anserine, inosine 5'-monophosphate, hypoxanthine, inosine and phospholipid, as well as amino acid and purine metabolism pathway connected to the improvements of meat quality, composition and taste of broilers by MG addition. In conclusion, these findings provide convincing evidence regarding the improvements of fresh meat quality, composition and taste of broilers by MG supplementation.

A bridge for short-chain fatty acids to affect inflammatory bowel disease, type 1 diabetes, and non-alcoholic fatty liver disease positively: by changing gut barrier.

PURPOSE: In previous studies, short-chain fatty acids (SCFAs) have been found to regulate gut microbiota and change gut barrier status, and the potential positive effects of SCFAs on inflammatory bowel disease (IBD), type 1 diabetes mellitus (T1D), and non-alcoholic fatty liver disease (NAFLD) have also been found, but the role of SCFAs in these three diseases is not clear. This review aims to summarize existing evidence on the effects of SCFAs on IBD, T1D, and NHFLD, and correlates them with gut barrier and gut microbiota (gut microbiota barrier). METHODS: A literature search in PubMed, Web of Science, Springer, and Wiley Online Library up to October 2020 was conducted for all relevant studies published. RESULTS: This is a retrospective review of 150 applied research articles or reviews. The destruction of gut barrier may promote the development of IBD, T1D, and NAFLD. SCFAs seem to maintain the gut barrier by promoting the growth of intestinal epithelial cells, strengthening the intestinal tight connection, and regulating the activities of gut microbiota and immune cells, which might result possible beneficial effects on the above three diseases at a certain dose. CONCLUSIONS: Influencing gut barrier health may be a bridge for SCFAs (especially butyrate) to have positive effects on IBD, T1D, and NAFLD. It is expected that this article can provide new ideas for the subsequent research on the treatment of diseases by SCFAs and help SCFAs be better applied to precise and personalized treatment.

Weight-Reducing Effect of Lactobacillus plantarum ZJUFT17 Isolated from Sourdough Ecosystem.

Lactobacillus plantarum ZJUFT17 (T17) is a potential probiotic bacterium isolated from Chinese traditional sourdough. The purpose of this study was to investigate its weight-reducing effects in mice fed a high-fat diet (HFD) and further to elucidate possible mechanisms. Male C57BL/6J mice fed HFD were given T17 (2-4×108 cfu) intragastrically for 10 weeks. The results showed that the administration of T17 significantly suppressed HFD-induced body weight gain, alleviated HFD-induced increase in serum lipids and decreased energy intake. The serum levels of obesity-related metabolic signaling molecules, including insulin, adiponectin, lipopolysaccharide (LPS) and the cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, were markedly improved. The 16S rRNA gene sequencing revealed that T17 administration dramatically modulated the gut microbiota, suppressing pathogenic and pro-inflammatory microbes and stimulating the microbes favoring anti-obesity. The weight-reducing efficacy of T17 may be explained by its ability to ameliorate systemic inflammation and insulin resistance mediated by gut microbiota. This study revealed that T17 could ameliorate obesity and the concomitant metabolic syndrome in mice and that the lactic acid bacteria in the sourdough ecosystem may also possess anti-obesity/weight-reducing properties.

Modulation of the Gut Microbiota during High-Dose Glycerol Monolaurate-Mediated Amelioration of Obesity in Mice Fed a High-Fat Diet.

Obesity and associated metabolic disorders are worldwide public health issues. The gut microbiota plays a key role in the pathophysiology of diet-induced obesity. Glycerol monolaurate (GML) is a widely consumed food emulsifier with antibacterial properties. Here, we explore the anti-obesity effect of GML (1,600 mg/kg of body weight) in high-fat diet (HFD)-fed mice. HFD-fed mice were treated with 1,600 mg/kg GML. Integrated microbiome, metabolome, and transcriptome analyses were used to systematically investigate the metabolic effects of GML, and antibiotic treatment was used to assess the effects of GML on the gut microbiota. Our data indicated that GML significantly reduced body weight and visceral fat deposition, improved hyperlipidemia and hepatic lipid metabolism, and ameliorated glucose homeostasis and inflammation in HFD-fed mice. Importantly, GML modulated HFD-induced gut microbiota dysbiosis and selectively increased the abundance of Bifidobacterium pseudolongum Antibiotic treatment abolished all the GML-mediated metabolic improvements. A multiomics (microbiome, metabolome, and transcriptome) association study showed that GML significantly modulated glycerophospholipid metabolism, and the abundance of Bifidobacterium pseudolongum strongly correlated with the metabolites and genes that participated in glycerophospholipid metabolism. Our results indicated that GML may be provided for obesity prevention by targeting the gut microbiota and regulating glycerophospholipid metabolism.

Protective effect of Bacillus amyloliquefaciens against Salmonella via polarizing macrophages to M1 phenotype directly and to M2 depended on microbiota.

Bacillus amyloliquefaciens SC06 (BaSC06), a potential probiotic, plays a positive role in animal growth performance and immune function. The aim of the present study was to investigate the protective effect of BaSC06 against Salmonella infection and its association with macrophage polarization. C57BL/6 mice were fed with or without a BaSC06-containing diet before Salmonella enterica Typhimurium (ST) challenge. Results showed that BaSC06 had a protective effect against ST inoculation and induced both M1 and M2 macrophage polarization in the cecum. An in vitro co-culture model demonstrated that BaSC06 promoted M1 polarization directly, and thus increased the phagocytosis and bactericidal activity against ST. In addition, adoptive transfer of bone marrow-derived macrophages (BMDMs) stimulated by BaSC06 significantly decreased the counts of ST in the spleen. Furthermore, 16S rRNA-based analysis of cecal content showed that BaSC06 significantly increased the proportion of Verrucomicrobia and decreased Bacterodetes. Transplantation of the fecal microbiota from BaSC06-treated animals promoted M2 macrophage polarization in the cecum and significantly relieved inflammation caused by ST. In conclusion, BaSC06 polarized macrophages to the M1 type directly resulting in excellent bactericidal activity. Meanwhile, the microbiota modified by BaSC06 can induce M2 polarization which ameliorates the inflammation caused by ST.

High-dose Glycerol Monolaurate Up-Regulated Beneficial Indigenous Microbiota without Inducing Metabolic Dysfunction and Systemic Inflammation: New Insights into Its Antimicrobial Potential.

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg-1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg-1) showed positive impacts on the anti-inflammatory TGF-ß1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg-1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg-1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.