Restricted intake of sulfur-containing amino acids reversed the hepatic injury induced by excess Desulfovibrio through gut-liver axis.

Diet is a key player in gut-liver axis. However, the effect of different dietary patterns on gut microbiota and liver functions remains unclear. Here, we used rodent standard chow and purified diet to mimic two common human dietary patterns: grain and plant-based diet and refined-food-based diet, respectively and explored their impacts on gut microbiota and liver. Gut microbiota experienced a great shift with notable increase in Desulfovibrio, gut bile acid (BA) levels elevated significantly, and liver inflammation was observed in mice fed with the purified diet. Liver inflammation and elevated gut BA levels also occurred in mice fed with the chow diet after receiving Desulfovibrio desulfuricans ATCC 29,577 (DSV). Restriction of sulfur-containing amino acids (SAAs) prevented liver injury mainly through higher hepatic antioxidant and detoxifying ability and reversed the elevated BA levels due to excess Desulfovibrio. Ex vivo fermentation of human fecal microbiota with primary BAs demonstrated that DSV enhanced production of secondary BAs. Higher concentration of both primary and secondary BAs were found in the gut of germ-free mice after receiving DSV. In conclusion, Restriction of SAAs in diet may become an effective dietary intervention to prevent liver injury associated with excess Desulfovibrio in the gut.

Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn's disease.

BACKGROUND: Crohn's disease (CD) is associated with changes in the microbiota, and murine models of CD-like ileo-colonic inflammation depend on the presence of microbial triggers. Increased abundance of unknown Clostridiales and the microscopic detection of filamentous structures close to the epithelium of Tnf ΔARE mice, a mouse model of CD-like ileitis pointed towards segmented filamentous bacteria (SFB), a commensal mucosal adherent bacterium involved in ileal inflammation. RESULTS: We show that the abundance of SFB strongly correlates with the severity of CD-like ileal inflammation in two mouse models of ileal inflammation, including Tnf ΔARE and SAMP/Yit mice. SFB mono-colonization of germ-free Tnf ΔARE mice confirmed the causal link and resulted in severe ileo-colonic inflammation, characterized by elevated tissue levels of Tnf and Il-17A, neutrophil infiltration and loss of Paneth and goblet cell function. Co-colonization of SFB in human-microbiota associated Tnf ΔARE mice confirmed that SFB presence is indispensable for disease development. Screening of 468 ileal and colonic mucosal biopsies from adult and pediatric IBD patients, using previously published and newly designed human SFB-specific primer sets, showed no presence of SFB in human tissue samples, suggesting a species-specific functionality of the pathobiont. Simulating the human relevant therapeutic effect of exclusive enteral nutrition (EEN), EEN-like purified diet antagonized SFB colonization and prevented disease development in Tnf ΔARE mice, providing functional evidence for the protective mechanism of diet in modulating microbiota-dependent inflammation in IBD. CONCLUSIONS: We identified a novel pathogenic role of SFB in driving severe CD-like ileo-colonic inflammation characterized by loss of Paneth and goblet cell functions in Tnf ΔARE mice. A purified diet antagonized SFB colonization and prevented disease development in Tnf ΔARE mice in contrast to a fiber-containing chow diet, clearly demonstrating the important role of diet in modulating a novel IBD-relevant pathobiont and supporting a direct link between diet and microbial communities in mediating protective functions. Video Abstract.

Short communication: the effects of a semi-synthetic diet with inclusion of black soldier fly larvae meal on health parameters of healthy adult cats.

In recent years, black soldier fly larvae meal (Hermetia illucens; BSFLM) has gained attention as a high value alternative protein source that is of great interest to the pet food industry. However, little is known regarding the effects of BSFLM on health parameters in adult cats. Thus, the objective of the current study was to determine the short-term effects of a semi-synthetic diet containing 4.6% inclusion of BSFLM on complete blood count (CBC) and serum biochemistry profile of healthy adult cats. Healthy adult male cats (n = 8; 1.4 yr) were fed the experimental diet for 21 d (experimental period) to maintain BW. Cats were washed in on a commercial diet and blood samples were collected before the start and at the end of the experimental period to measure gross health parameters. Results were analyzed as one-way ANOVA using the GLIMMIX procedure in SAS with cat as a random effect (SAS v. 9.4, The SAS Institute, Cary, NC). Cats lost an average of 5% of their BW (P = 0.0003) due to a concurrent decrease in food intake. A significant increase of alanine aminotransferase, chloride, potassium, sodium, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration was observed on day 21 vs. baseline (P < 0.05). In contrast, albumin, amylase, calcium, cholesterol, eosinophil, lymphocyte, monocyte, mean platelet volume, red blood cells, total protein, total solid proteins, and urea decreased over time (P < 0.05). However, all CBC and serum biochemistry parameters stayed within reference range for adult cats, with exception of glucose and mean corpuscular hemoglobin concentration that were above and below the reference range, respectively. Transient increases in glucose concentrations were likely due to sedation with dexmedetomidine prior to blood collection. The changes observed over time in the aforementioned parameters are likely due to changes in macronutrient composition of the diets offered prior to and during the experimental period (commercial diet vs. semi-synthetic diet, respectively) and cannot be attributed solely to a unique property of BSFLM. In conclusion, cats fed a semi-synthetic diet containing 4% BSFLM inclusion for 21 d remained healthy with no clinically relevant changes in CBC and serum biochemistry parameters. Further research should focus on longer term feeding studies and the ability of BSFLM to support the health and well-being of cats.

Targeted Nutrient Modifications in Purified Diets Differentially Affect Nonalcoholic Fatty Liver Disease and Metabolic Disease Development in Rodent Models.

Nonalcoholic fatty liver disease (NAFLD) is a complex spectrum of disorders ranging from simple benign steatosis to more aggressive forms of nonalcoholic steatohepatitis (NASH) and fibrosis. Although not every patient with NAFLD/NASH develops liver complications, if left untreated it may eventually lead to cirrhosis and hepatocellular carcinoma. Purified diets formulated with specific nutritional components can drive the entire spectrum of NAFLD in rodent models. Although they may not perfectly replicate the clinical and histological features of human NAFLD, they provide a model to gain further understanding of disease progression in humans. Owing to the growing demand of diets for NAFLD research, and for our further understanding of how manipulation of dietary components can alter disease development, we outlined several commonly used dietary approaches for rodent models, including mice, rats, and hamsters, time frames required for disease development and whether other metabolic diseases commonly associated with NAFLD in humans occur.

Coordinated cytochrome P450 expression in mouse liver and intestine under different dietary conditions during liver regeneration after partial hepatectomy.

Liver resection is performed to remove tumors in patients with liver cancer, but the procedure's suitability depends on the regenerative ability of the liver. It is important to consider the effects of exogenous factors, such as diets, on liver regeneration for the recovery of function. The evaluation of drug metabolism during liver regeneration is also necessary because liver dysfunction is generally observed after the operation. Here, we investigated the influence of a purified diet (AIN-93G) on liver regeneration and changes in the mRNA expression of several cytochrome P450 (CYP) isoforms in the liver and small intestine using a two-thirds partial hepatectomy (PH) mouse model fed with a standard diet (MF) and a purified diet. Liver regeneration was significantly delayed in the purified diet group relative to that in the standard diet group. The liver Cyp2c55 and Cyp3a11 expression was increased at 3 day after PH especially in the purified diet group. Bile acid may partly cause the differences in liver regeneration and CYP expression between two types of diets. On the other hand, Cyp3a13 expression in the small intestine was transiently increased at day 1 after PH in both diet groups. The findings suggest that compensatory induction of the CYP expression occurred in the small intestine after attenuation of drug metabolism potential in the liver. The present results highlight the importance of the relationship between liver regeneration, drug metabolism, and exogenous factors for the effective treatment, including surgery and medication, in patients after liver resection or transplantation.

The Impact of Fructo-Oligosaccharides on Gut Permeability and Inflammatory Responses in the Cecal Mucosa Quite Differs between Rats Fed Semi-Purified and Non-Purified Diets.

The effects of fructo-oligosaccharides (FOS) on gut-barrier function are still controversial in human and animal studies. Diet conditions would be a major factor for the controversy in animal studies. We fed rats a semi-purified (SP) or a non-purified diet (NP) with or without FOS (60 g/kg diet) for 9 (experiment 1) or 10 d (experiment 2). We assessed microbial fermentation, gut permeability, and inflammatory responses in the cecum (experiment 1), and mucus layer in the cecum, intestinal transit time and microbiota composition (experiment 2). FOS supplementation induced a very acidic fermentation due to the accumulation of lactate and succinate in SP, while short-chain fatty acids were major products in NP. Gut permeability estimated by urinary chromium-EDTA excretion, bacterial translocation into mesenteric lymph nodes, myeloperoxidase activity, and expressions of the inflammatory cytokine genes in the cecal mucosa were greater in SP+FOS than in SP, but these alterations were not observed between NP and NP+FOS (experiment 1). FOS supplementation destroyed the mucus layer on the epithelial surface in SP, but not in NP. Intestinal transit time was 3-fold longer in SP+FOS than in SP, but this was not the case between NP and NP+FOS. Lower species richness of cecal microbiota was manifest solely in SP+FOS (experiment 2). These factors suggest that impact of FOS on gut permeability and inflammatory responses in the cecal mucosa quite differs between SP and NP. Increased gut permeability in SP+FOS could be evoked by the disruption of the mucus layer due to stasis of the very acidic luminal contents.

Safety assessment of genetically modified milk containing human beta-defensin-3 on rats by a 90-day feeding study.

In recent years, transgenic technology has been widely applied in many fields. There is concern about the safety of genetically modified (GM) products with the increased prevalence of GM products. In order to prevent mastitis in dairy cows, our group produced transgenic cattle expressing human beta-defensin-3 (HBD3) in their mammary glands, which confers resistance to the bacteria that cause mastitis. The milk derived from these transgenic cattle thus contained HBD3. The objective of the present study was to analyze the nutritional composition of HBD3 milk and conduct a 90-day feeding study on rats. Rats were divided into 5 groups which consumed either an AIN93G diet (growth purified diet for rodents recommended by the American Institute of Nutrition) with the addition of 10% or 30% HBD3 milk, an AIN93G diet with the addition of 10% or 30% conventional milk, or an AIN93G diet alone. The results showed that there was no difference in the nutritional composition of HBD3 and conventional milk. Furthermore, body weight, food consumption, blood biochemistry, relative organ weight, and histopathology were normal in those rats that consumed diets containing HBD3. No adverse effects were observed between groups that could be attributed to varying diets or gender.

Impact of basal diet on dextran sodium sulphate (DSS)-induced colitis in rats.

PURPOSE: Dextran sodium sulphate (DSS)-induced colitis is a widely used model for inflammatory bowel disease. However, various factors including nutrition may affect the development of this colitis. This study aimed to compare and characterize the impact of purified and non-purified basal diets on the development of DSS-induced colitis in the rat. METHODS: Wistar rats were fed a non-purified or a semi-synthetic purified diet for 21 days. Colitis was then induced in half of the rats by administration of DSS in drinking water (4% w/v) during the last 7 days of experimentation. At the end of the experimental period, colon sections were taken for histopathological examination, determination of various markers of inflammation (myeloperoxidase: MPO, cytokines) and oxidative stress (superoxide dismutase: SOD, catalase: CAT, glutathione peroxidase: GPx and glutathione reductase: GRed activities), and evaluation of the expression of various genes implicated in this disorder. RESULTS: DSS ingestion induced a more marked colitis in animals receiving the purified diet, as reflected by higher histological score and increased MPO activity. A significant decrease in SOD and CAT activities was also observed in rats fed the purified diet. Also, in these animals, administration of DSS induced a significant increase in interleukin (IL)-1α, IL-1ß and IL-6. In addition, various genes implicated in inflammation were over-expressed after ingestion of DSS by rats fed the purified diet. CONCLUSIONS: These results show that a purified diet promotes the onset of a more severe induced colitis than a non-purified one, highlighting the influence of basal diet in colitis development.