Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis

Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.     

Impact of chicory inclusion in a cereal-based diet on digestibility,organ size and faecal microbiota in growing pigs

A total of 30 7-week-old pigs were used to evaluate the effects of chicory inclusion on digestibility, digestive organ size and faecal microbiota. Five diets were formulated: a cereal-based control diet and four diets with inclusion of 80 and 160 g/kg chicory forage (CF80 and CF160), 80 g/kg chicory root (CR80) and a mix of 80 g/kg forage and 80 g/kg chicory root (CFR). Generally, the pigs showed a high growth rate and feed intake, and no differences between the different diets were observed. The coefficients of total tract apparent digestibility (CTTAD) of energy, organic matter and CP did not differ between the control and CF80, whereas they were impaired in diet CF160. The CTTAD of non-starch polysaccharides and especially the uronic acids were higher (P < 0.05) with chicory inclusion, with highest (P < 0.05) values for diet CF160. Coliform counts were lower and lactobacilli : coliform ratio was higher (P < 0.05) in diet CFR than in the control. Global microbial composition was investigated by terminal restriction fragment length polymorphism combined with cloning and sequencing. Analysis of gut microbiota pattern revealed two major clusters where diet CF160 differed from the control and CR80 diet. Chicory forage diets were correlated with an increased relative abundance of one species related to Prevotella and decreased abundance of two other species related to Prevotella. For diet CFR, the relative abundance of Lactobacillus johnsonii was higher than in the other diets. This study shows that both chicory forage and root can be used as fibre sources in pig nutrition and that they modulate the composition of the gut microbiota differently.     

Effects of Bacillus subtilis and antibiotic growth promoters on the growth performance,intestinal function and gut microbiota of pullets from 0 to 6 weeks

The development of digestive organs and the establishment of gut microbiota in pullets play an important role throughout life. This study was conducted to investigate the effects of Bacillus subtilis (BS) on growth performance, intestinal function and gut microbiota in pullets from 0 to 6 weeks of age. Hy-line Brown laying hens (1-day-old, n = 504) were randomly allotted into four diets with a 2 × 2 factorial design: (1) basal diet group (control); (2) antibiotics group (AGP), the basal diet supplemented with 20 mg/kg Bacitracin Zinc and 4 mg/kg Colistin Sulphate; (3) BS group, the basal diet supplemented with 500 mg/kg BS and (4) mixed group, the basal diet supplemented with both AGP and BS. As a result, when BS was considered the main effect, BS addition (1) reduced the feed conversion ratio at 4 to 6 weeks (P < 0.05); (2) decreased duodenal and jejunal crypt depth at 3 weeks; (3) increased the villus height : crypt depth (V : C) ratio in the duodenum at 3 weeks and jejunal villus height at 6 weeks and (4) increased sucrase mRNA expression in the duodenum at 3 weeks as well as the jejunum at 6 weeks, and jejunal maltase and aminopeptidase expression at 3 weeks. When AGP was considered the main effect, AGP supplementation (1) increased the V : C ratio in the ileum at 3 weeks of age; (2) increased sucrase mRNA expression in the duodenum at 3 weeks as well as the ileum at 6 weeks, and increased maltase expression in the ileum. The BS × AGP interaction was observed to affect average daily feed intake at 4 to 6 weeks, and duodenal sucrase and jejunal maltase expression at 3 weeks. Furthermore, dietary BS or AGP addition improved caecal microbial diversity at 3 weeks, and a BS × AGP interaction was observed (P < 0.05) for the Shannon and Simpson indexes. At the genus level, the relative abundance of Lactobacillus was found to be higher in the mixed group at 3 weeks and in the BS group at 6 weeks. Moreover, Anaerostipes, Dehalobacterium and Oscillospira were also found to be dominant genera in pullets with dietary BS addition. In conclusion, BS could improve intestinal morphology and change digestive enzyme relative expression and caecum microbiota, thereby increasing the efficiency of nutrient utilization. Our findings suggested that BS might have more beneficial effects than AGP in the study, which would provide theoretical evidence and new insight into BS application in layer pullets.     

Evaluation of early feed access and algal extract on growth performance,organ development,gut microbiota and vaccine-induced antibody responses in broiler chickens

Hatching concepts such as on-farm hatching provide an opportunity to supply newly hatched chickens with optimal nutrition that support growth and development of a healthy gut. Brown algae contain bioactive compounds, especially laminarin and fucoidan that may improve intestinal health and immune responses. This study aimed to examine the effects of early access to feed and water posthatch and feed supplementation with algal extract rich in laminarin from Laminaria digitata, on growth performance, organ and microbiota development and antibody production. A total of 432 Ross 308 chicks were allotted to 36 rearing pens in a 2 × 3 factorial design with two hatching treatments and three dietary treatments. During chick placement, half of the pens were directly provided access to feed and water (Early) while half of the pens were deprived of feed and water for 38 h (Late). The chicks were fed three different starter diets until day 6; a wheat-soybean meal-based control diet, a diet with low inclusion of algal extract (0.057%) and a diet with high inclusion of algal extract (0.114%). Feed intake and BW were registered on pen basis at placement, days 1, 6, 12, 19, 26, 33 and 40. To induce antibody responses, all chicks were vaccinated against avian pneumovirus on day 10. Three chicks per pen were selected as focal animals and used for blood sampling on days 10 and 39. On days 6, 19, and 40, two birds per pen were killed and used for organ measurement and caecal digesta sampling for gut microbiota analysis using the Illumina Miseq PE 250 sequencing platform. Results showed that algal extract did not influence gut microbiota, gut development or vaccine-induced antibody responses. However, during the first 38 h, early-fed chicks consumed on average 19.6 g of feed and gained 27% in BW, while late-fed chicks lost 9.1% in BW which lowered BW and feed intake throughout the study (P < 0.05). Late chicks also had longer relative intestine, higher relative (g/kg BW) weight of gizzard and proventriculus but lower relative bursa weight on day 6 (P < 0.05). No effects of hatching treatment on microbiota or antibody response were detected. The microbiota was affected by age, where alpha diversity increased with age. In conclusion, this study showed that early access to feed but not algal extract improved the growth performance throughout the 40-day growing period, and stimulated early bursa development.     

Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in nonobese diabetic mice

Impairment of gut epithelial barrier function is a key predisposing factor for inflammatory bowel disease, type 1 diabetes (T1D) and related autoimmune diseases. We hypothesized that maternal obesity induces gut inflammation and impairs epithelial barrier function in the offspring of nonobese diabetic (NOD) mice. Four-week-old female NOD/ShiLtJ mice were fed with a control diet (CON; 10% energy from fat) or a high-fat diet (HFD; 60% energy from fat) for 8 weeks to induce obesity and then mated. During pregnancy and lactation, mice were maintained in their respective diets. After weaning, all offspring were fed the CON diet. At 16 weeks of age, female offspring were subjected to in vivo intestinal permeability test, and then ileum was sampled for biochemical analyses. Inflammasome mediators, activated caspase-1 and mature forms of interleukin (IL)-1β and IL-18 were enhanced in offspring of obese mothers, which was associated with elevated serum tumor necrosis factor α level and inflammatory mediators. Consistently, abundance of oxidative stress markers including catalase, peroxiredoxin-4 and superoxide dismutase 1 was heightened in offspring ileum (P<.05). Furthermore, offspring from obese mothers had a higher intestinal permeability. Morphologically, maternal obesity reduced villi/crypt ratio in the ileum of offspring gut. In conclusion, maternal obesity induced inflammation and impaired gut barrier function in offspring of NOD mice. The enhanced gut permeability in HFD offspring might predispose them to the development of T1D and other gut permeability-associated diseases.     

Changes in Gut Microbiota in Rats Fed a High Fat Diet Correlate with Obesity-Associated Metabolic Parameters

The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD) at the phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks) to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (P<0.0001), this being compensated by an increase in abundance of propionate/acetate producing species. To further understand the influence of these species on the development of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD.     

Microbial Enterotypes,Inferred by the Prevotella-to-Bacteroides Ratio,Remained Stable during a 6-Month Randomized Controlled Diet Intervention with the New Nordic Diet

It has been suggested that the human gut microbiota can be divided into enterotypes based on the abundance of specific bacterial groups; however, the biological significance and stability of these enterotypes remain unresolved. Here, we demonstrated that subjects (n = 62) 18 to 65 years old with central obesity and components of metabolic syndrome could be grouped into two discrete groups simply by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Furthermore, we showed that these groups remained stable during a 6-month, controlled dietary intervention, where the effect of consuming a diet in accord with the new Nordic diet (NND) recommendations as opposed to consuming the average Danish diet (ADD) on the gut microbiota was investigated. In this study, subjects (with and without stratification according to P/B ratio) did not reveal significant changes in 35 selected bacterial taxa quantified by quantitative PCR (ADD compared to NND) resulting from the dietary interventions. However, we found higher total plasma cholesterol within the high-P/B group than in the low-P/B group after the intervention. We propose that stratification of humans based simply on their P/B ratio could allow better assessment of possible effects of interventions on the gut microbiota and physiological biomarkers.     

Chemically Defined Diet Alters the Protective Properties of Fructo-Oligosaccharides and Isomalto-Oligosaccharides in HLA-B27 Transgenic Rats

Non-digestible oligosaccharides (NDO) were shown to reduce inflammation in experimental colitis, but it remains unclear whether microbiota changes mediate their colitis-modulating effects. This study assessed intestinal microbiota and intestinal inflammation after feeding chemically defined AIN-76A or rat chow diets, with or without supplementation with 8 g/kg body weight of fructo-oligosaccharides (FOS) or isomalto-oligosaccharides (IMO). The study used HLA-B27 transgenic rats, a validated model of inflammatory bowel disease (IBD), in a factorial design with 6 treatment groups. Intestinal inflammation and intestinal microbiota were analysed after 12 weeks of treatment. FOS and IMO reduced colitis in animals fed rat chow, but exhibited no anti-inflammatory effect when added to AIN-76A diets. Both NDO induced specific but divergent microbiota changes. Bifidobacteria and Enterobacteriaceae were stimulated by FOS, whereas copy numbers of Clostridium cluster IV were decreased. In addition, higher concentrations of total short-chain fatty acids (SCFA) were observed in cecal contents of rats on rat chow compared to the chemically defined diet. AIN-76A increased the relative proportions of propionate, iso-butyrate, valerate and iso-valerate irrespective of the oligosaccharide treatment. The SCFA composition, particularly the relative concentration of iso-butyrate, valerate and iso-valerate, was associated (P≤0.004 and r≥0.4) with increased colitis and IL-1 β concentration of the cecal mucosa. This study demonstrated that the protective effects of fibres on colitis development depend on the diet. Although diets modified specific cecal microbiota, our study indicates that these changes were not associated with colitis reduction. Intestinal inflammation was positively correlated to protein fermentation and negatively correlated with carbohydrate fermentation in the large intestine.     

Bilberry pomace in rabbit nutrition: effects on growth performance,apparent digestibility,caecal traits,bacterial community and antioxidant status

Agricultural by-products could be used as alternative raw materials in rabbit nutrition as they have been found to be highly nutritious and low cost feeding sources. The aim of this study was to estimate the nutritive value and potential use of bilberry pomace (BP) for growing rabbits. A total of 144 Grimaud rabbits (35 days old) were allotted to four groups and fed with a diet containing increasing level of BP: BP0 (basal diet), BP5, BP10 and BP15 containing 0, 50, 100 and 150 g/kg respectively. Growth trial lasted 48 days; apparent digestibility was evaluated, starting at 46 days of age, over 4 consecutive days. The nutritive value of BP was measured using the mean digestibility of the experimental diets. At 83 days of age, rabbits were slaughtered: blood, and liver and kidney samples were collected in order to determine the blood parameters and the antioxidant enzyme activities of the tissues. Moreover, caecal content was sampled and gut microbiota assessed by means of amplicon-based high-throughput 16S rRNA sequencing and PCR-denaturing gradient gel electrophoresis. The digestible protein was estimated to 104 g/kg of DM while digestible energy to 9.44 MJ/kg DM for incorporation rate up to 150 g/kg. During the finishing period, average daily feed intake and feed conversion ratio showed linear response to BP increase (P=0.008 and <0.001, respectively). During all the period, both parameters decreased linearly and quadratically with increasing BP inclusion levels (P<0.001) up to 100 g/kg of BP. A significant effect of the antioxidant status was found in the kidneys and liver (P<0.05) where the glutathione peroxidase activity increased as the BP increased. As far as gut microbiota is concerned, BP increased the relative abundance of the Clostridium, Oscillospira, Ruminococcus and Ruminococcaceae species which were clearly associated with the BP inclusion level. In conclusion, BP showed a potential use as an alternative protein and fibre sources for growing rabbits.     

Gut microbiome composition is linked to whole grain-induced immunological improvements

The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on fecal microbial ecology and blood markers of inflammation, glucose and lipid metabolism. All treatments increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples. The inclusion of WGB enriched the genera Roseburia, Bifidobacterium and Dialister, and the species Eubacterium rectale, Roseburia faecis and Roseburia intestinalis. Whole grains, and especially the BR+WGB treatment, reduced plasma interleukin-6 (IL-6) and peak postprandial glucose. Shifts in the abundance of Eubacterium rectale were associated with changes in the glucose and insulin postprandial response. Interestingly, subjects with greater improvements in IL-6 levels harbored significantly higher proportions of Dialister and lower abundance of Coriobacteriaceae. In conclusion, this study revealed that a short-term intake of whole grains induced compositional alterations of the gut microbiota that coincided with improvements in host physiological measures related to metabolic dysfunctions in humans.     

An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice

Lipopolysaccharide endotoxin is the only known bacterial product which, when subcutaneously infused into mice in its purified form, can induce obesity and insulin resistance via an inflammation-mediated pathway. Here we show that one endotoxin-producing bacterium isolated from a morbidly obese human''s gut induced obesity and insulin resistance in germfree mice. The endotoxin-producing Enterobacter decreased in relative abundance from 35% of the volunteer''s gut bacteria to non-detectable, during which time the volunteer lost 51.4 kg of 174.8 kg initial weight and recovered from hyperglycemia and hypertension after 23 weeks on a diet of whole grains, traditional Chinese medicinal foods and prebiotics. A decreased abundance of endotoxin biosynthetic genes in the gut of the volunteer was correlated with a decreased circulating endotoxin load and alleviated inflammation. Mono-association of germfree C57BL/6J mice with strain Enterobacter cloacae B29 isolated from the volunteer''s gut induced fully developed obesity and insulin resistance on a high-fat diet but not on normal chow diet, whereas the germfree control mice on a high-fat diet did not exhibit the same disease phenotypes. The Enterobacter-induced obese mice showed increased serum endotoxin load and aggravated inflammatory conditions. The obesity-inducing capacity of this human-derived endotoxin producer in gnotobiotic mice suggests that it may causatively contribute to the development of obesity in its human host.     

Effects of glucose oxidase and its combination with B. amyloliquefaciens SC06 on intestinal microbiota,immune response and antioxidative capacity in broilers

Glucose oxidase (GOD) is an aerobic dehydrogenase, which catalyses the oxidation of β-D-glucose to gluconic acid and hydrogen peroxide. This study aimed to investigate the effects of dietary glucose oxidase and its combined effects with Bacillus amyloliquefaciens SC06 (BaSC06) on the intestinal microbiota, immune function and antioxidant capacity of broilers. One-day-old male Lingnan yellow-feathered broilers (n = 720) were randomly assigned to four treatment groups: Control group (basal diet), Anti group (basal diet supplemented with 200 mg/kg enramycin), GOD group (basal diet supplemented with 75 U/kg GOD), and combination of GOD and BaSC06 (GB) group (GOD diet (75 U/kg) supplemented with 1 × 10⁸ colony-forming units BaSC06/kg feed), with six replicates per group and 30 birds per replicate. The experiment was conducted over 52 days. The results indicated a significant decrease in α-diversity (Observed species, Chao1, PD_whole_tree and Shannon) with GOD treatment, compared with the control group. GB treatment also significantly decreased the Shannon index of cecal microbiota. GOD treatment significantly decreased the α-diversity, whereas GB treatment significantly increased these indices except for the Chao1 index, compared with the Anti group. Compared with the control group, the relative abundance of Bacteroides in the GOD and GB groups was significantly increased, whereas a decrease in Firmicutes was observed. Compared with the Anti group, GOD treatment significantly increased the relative abundances of Bacteroides and Lactobacillales, while GB treatment significantly increased Lactobacillales and decreased Proteobacteria levels. In addition, GOD treatment significantly decreased interleukin-10 and interferon-γ levels, compared with the control group. In contrast, GB treatment significantly downregulated interferon-γ levels and upregulated secretory immunoglobulin A, transforming growth factor-β and interleukin-2 expression in the jejunal mucosa. GOD treatment significantly decreased transforming growth factor-β and interleukin-10 levels, whereas GB treatment markedly increased interferon-γ expression in the jejunal mucosa compared with the Anti group. Furthermore, GB treatment significantly increased the total antioxidant capability levels and the total superoxide dismutase (T-SOD) and catalase (CAT) activities compared with the control group. Meanwhile, GOD treatment significantly increased glutathione peroxidase (GSH-Px) activity in the jejunal mucosa. Total superoxide dismutase, GSH-Px and CAT activities in the Anti group were higher than in the GOD and GB groups. The malondialdehyde levels in the control group were the highest among all groups. In conclusion, our results indicated that supplementation with GOD alone and its combination with BaSC06 in diet could increase antioxidant capacity, immune function and improve the intestinal microbiota composition of broilers. Combination treatment with GOD with BaSC06 exerted stronger effects than GOD treatment only.     

Traditional Chinese Medicine Ganshuang Granules Attenuate CCl4-Induced Hepatic Fibrosis by Modulating Gut Microbiota

Gut dysbiosis contributes to hepatic fibrosis. Emerging evidence revealed the major role of traditional Chinese medicine (TCM) in gut microbiota homeostasis. Here, we aimed to investigate the anti-fibrotic activity and underlying mechanism of ganshuang granules (GS), particularly regarding gut microbiota homeostasis. CCl₄-induced hepatic fibrosis models were allocated into 4 groups receiving normal saline (model), 1.0, 2.0, or 4.0 g/kg GS for 5 weeks. As result, GS treatment alleviated liver injury in CCl₄-induced hepatic fibrosis, presenting as decreases of the liver index, alanine aminotransferase, and aspartate transaminase. Histological staining and expression revealed that the enhanced oxidative stress, inflammatory and hepatic fibrosis in CCl₄-induced models were attenuated by GS. Immunohistochemical staining showed that tight junction-associated proteins in intestinal mucosa were up-regulated by GS. 16S rRNA sequencing showed that GS rebalanced the gut dysbiosis manifested as improving alpha and beta diversity of gut microbiota, reducing the ratio of Firmicutes to Bacteroidetes, and regulating the relative abundance of various bacteria. In summary, GS decreased the intestinal permeability and rebalanced the gut microbiota to reduce the oxidative stress and inflammation, eventually attenuating CCl₄-induced hepatic fibrosis.     

Comparative analysis of the ileal bacterial composition of post-weaned pigs fed different high-quality protein sources

To further understand the contribution of feedstuff ingredients to gut health in swine, gut histology and intestinal bacterial profiles associated with the use of two high-quality protein sources, microbially enhanced soybean meal (MSBM) and Menhaden fishmeal (FM) were assessed. Weaned pigs were fed one of three experimental diets: (1) basic diet containing corn and soybean meal (Negative Control (NEG)), (2) basic diet + fishmeal (FM; Positive Control (POS)) and (3) basic diet + MSBM (MSBM). Phase I POS and MSBM diets (d 0 to d 7 post-wean) included FM or MSBM at 7.5%, while Phase II POS and MSBM diets (d 8 to d 21) included FM or MSBM at 5.0%. Gastrointestinal tissue and ileal digesta were collected from euthanised pigs at d 21 (eight pigs/diet) to assess gut histology and intestinal bacterial profiles, respectively. Data were analysed using Proc Mixed in SAS, with pig as the experimental unit and pig (treatment) as the random effect. Histological and immunohistochemical analyses of stomach and small intestinal tissue using haematoxylin–eosin, Periodic Acid Schiff/Alcian blue and inflammatory cell staining did not reveal detectable differences in host response to dietary treatment. Ileal bacterial composition profiles were obtained from next-generation sequencing of PCR generated amplicons targeting the V1 to V3 regions of the 16S rRNA gene. Lactobacillus-affiliated sequences were found to be the most highly represented across treatments, with an average relative abundance of 64.0%, 59.9% and 41.80% in samples from pigs fed the NEG, POS and MSBM diets, respectively. Accordingly, the three most abundant Operational Taxonomic Units (OTUs) were affiliated to Lactobacillus, showing a distinct abundance pattern relative to dietary treatment. One OTU (SD_Ssd_00001), most closely related to Lactobacillus amylovorus, was found to be more abundant in NEG and POS samples compared to MSBM (23.5% and 35.0% v. 9.2%). Another OTU (SD_Ssd_00002), closely related to Lactobacillus johnsonii, was more highly represented in POS and MSBM samples compared to NEG (14.0% and 15.8% v. 0.1%). Finally, OTU Sd_Ssd-00011, highest sequence identity to Lactobacillus delbrueckii, was found in highest abundance in ileal samples from MSBM-fed pigs (1.9% and 3.3% v. 11.3, in POS, NEG and MSBM, respectively). There was no effect of protein source on bacterial taxa to the genus level or diversity based on principal component analysis. Dietary protein source may provide opportunity to enhance presence of specific members of Lactobacillus genus that are associated with immune-modulating properties without altering overall intestinal bacterial diversity.     

Curcuma longa Extract Associated with White Pepper Lessens High Fat Diet-Induced Inflammation in Subcutaneous Adipose Tissue

Background

Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity.

Methodology/Principal Findings

Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation.

Conclusions/Significance

These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition.     

Intake of Meat Proteins Substantially Increased the Relative Abundance of Genus Lactobacillus in Rat Feces

Diet has been shown to have a critical influence on gut bacteria and host health, and high levels of red meat in diet have been shown to increase colonic DNA damage and thus be harmful to gut health. However, previous studies focused more on the effects of meat than of meat proteins. In order to investigate whether intake of meat proteins affects the composition and metabolic activities of gut microbiota, feces were collected from growing rats that were fed with either meat proteins (from beef, pork or fish) or non-meat proteins (casein or soy) for 14 days. The resulting composition of gut microbiota was profiled by sequencing the V4-V5 region of the 16S ribosomal RNA genes and the short chain fatty acids (SCFAs) were analyzed using gas chromatography. The composition of gut microbiota and SCFA levels were significantly different between the five diet groups. At a recommended dose of 20% protein in the diet, meat protein-fed rats had a higher relative abundance of the beneficial genus Lactobacillus, but lower levels of SCFAs and SCFA-producing bacteria including Fusobacterium, Bacteroides and Prevotella, compared with the soy protein-fed group. Further work is needed on the regulatory pathways linking dietary protein intake to gut microbiota.     

Liraglutide modulates gut microbiota and reduces NAFLD in obese mice

Metabolic disorders such as insulin resistance and diabetes are associated with obesity and nonalcoholic fatty liver disease (NAFLD). The aggressive form of a fatty liver disease may progress to cirrhosis and hepatocellular carcinoma. Furthermore, recent studies demonstrated that there is a dysbiosis in the gut microbiota associated with early stages of metabolic disease. Therefore, the identification and repurposing of drugs already used to treat insulin resistance may be an excellent option for other disorders. We evaluated the effect of liraglutide on obesity, NAFLD and gut microbiota modulation in two different animal models of obesity: the ob/ob mice and the high-fat diet (HFD)-fed mice. Liraglutide treatment induced significant weight loss in both obesity models, showed improvements in glycemic parameters and reduced inflammatory cell infiltration in the cecum and the liver. In ob/ob mice, the liraglutide treatment was able to reduce the accumulation of liver fat by 78% and reversed steatosis in the HFD mice. The gut microbiota analysis showed that liraglutide changed the overall composition as well as the relative abundance of weight-relevant phylotypes such as a reduction of Proteobacteria and an increase of Akkermansia muciniphila in the treated HFD group. We show that liraglutide can lead to weight loss and gut microbiota modulations, and is associated with an improvement of NAFLD. Furthermore, by generating a profile of the intestinal microbiota, we compiled a list of potential bacterial targets that may modulate metabolism and induce a metabolic profile that is considered normal or clinically controlled.     

首荟通便胶囊对术后肠麻痹小鼠肠道功能的影响及机制研究

探讨首荟通便（Shou-Hui Tongbian,SHTB）胶囊对小鼠术后肠麻痹（postoperative ileus,POI）的作用,并从肠道菌群平衡方面探讨其可能的作用机制。

采用经典小肠干扰术建立小鼠POI模型,将30只小鼠随机分成对照组（Control组）、模型组（POI组）、阳性参照莫沙必利组（MSBL组）、SHTB胶囊低剂量组（SHTB-L组）和SHTB胶囊高剂量组（SHTB-H组）,每组6只。Control组和POI组小鼠灌胃生理盐水、MSBL组小鼠灌胃莫沙必利溶液（2.6 mg/kg）、SHTB-L组与SHTB-H组小鼠灌胃SHTB溶液（0.619 g/kg、1.238 g/kg）,每天1次,连续给药2 d。采用墨汁推进法检测小鼠的肠道蠕动能力;应用H&;E染色法观察小鼠肠道组织结构;利用16S rRNA基因高通量测序技术解析肠道菌群结构并确定SHTB胶囊发挥作用的关键菌。

与Control组相比,POI组小鼠肠道蠕动能力显著减弱（q=7.263,P＜0.001）,小肠黏膜中性粒细胞和淋巴细胞增多并伴有充血,组织发生水肿,肠道菌群物种总数降低,有益菌Parvibacter等的相对丰度显著降低（t=3.340,P=0.008）,有害菌Rikenellaceae_RC9_gut_group等的相对丰度显著升高（U=2,P=0.009）;药物治疗后上述变化有不同程度的减轻,与POI组相比,SHTB-L组、SHTB-H组和MSBL组小鼠肠道蠕动能力均显著提升（均P＜0.010）,炎症、水肿和充血等肠道病理改变明显好转;SHTB组小鼠肠道菌群物种总数有所提高,其中Parvibacter等的相对丰度显著升高（U=5,P=0.041）,Rikenellaceae_RC9_gut_group相对丰度显著降低（U=3,P=0.015）。

SHTB胶囊可通过调节小肠黏膜关键菌的平衡来改善POI小鼠肠道病理改变,促进肠道蠕动。

     

Reducing protein content in the diet of growing goats: implications for nitrogen balance,intestinal nutrient digestion and absorption,and rumen microbiota

Reducing dietary CP content is an effective approach to reduce animal nitrogen excretion and save protein feed resources. However, it is not clear how reducing dietary CP content affects the nutrient digestion and absorption in the gut of ruminants, therefore it is difficult to accurately determine how much reduction in dietary CP content is appropriate. This study was conducted to investigate the effects of reduced dietary CP content on N balance, intestinal nutrient digestion and absorption, and rumen microbiota in growing goats. To determine N balance, 18 growing wether goats (25.0 ± 0.5 kg) were randomly assigned to one of three diets: 13.0% (control), 11.5% and 10.0% CP. Another 18 growing wether goats (25.0 ± 0.5 kg) were surgically fitted with ruminal, proximate duodenal, and terminal ileal fistulae and were randomly assigned to one of the three diets to investigate intestinal amino acid (AA) absorption and rumen microbiota. The results showed that fecal and urinary N excretion of goats fed diets containing 11.5% and 10.0% CP were lower than those of goats fed the control diet (P < 0.05). When compared with goats fed the control diet, N retention was decreased and apparent N digestibility in the entire gastrointestinal tract was increased in goats fed the 10% CP diet (P < 0.05). When compared with goats fed the control diet, the duodenal flow of lysine, tryptophan and phenylalanine was decreased in goats fed the 11.5% CP diet (P < 0.05) and that of lysine, methionine, tryptophan, phenylalanine, leucine, glutamic acid, tyrosine, essential AAs (EAAs) and total AAs (TAAs) was decreased in goats fed the 10.0% CP diet (P < 0.05). When compared with goats fed the control diet, the apparent absorption of TAAs in the small intestine was increased in goats fed the 11.5% CP diet (P < 0.05) and that of isoleucine, serine, cysteine, EAAs, non-essential AAs, and TAAs in the small intestine was increased in goats fed the 10.0% CP diet (P < 0.05). When compared with goats fed the control diet, the relative richness of Bacteroidetes and Fibrobacteres was increased and that of Proteobacteria and Synergistetes was decreased in the rumen of goats fed a diet with 10.0% CP. In conclusion, reducing dietary CP content reduced N excretion and increased nutrient utilization by improving rumen fermentation, enhancing nutrient digestion and absorption, and altering rumen microbiota in growing goats.