High-fat Low-fiber Diet Research Articles

Dietary ingredient change induces a transient MyD88-dependent mucosal enteric glial cell response and promotes obesity

ABSTRACT Objective Consumption of a modern Western-type high-fat low-fiber diet increases the risk of obesity. However, how a host responds to such a diet, especially during the early period of dietary transition from a previous low-fat and fiber-rich diet, remains poorly explored. Methods Wild-type C57BL/6 mice were fed a normal chow diet or a high-fat diet. Enteric glial cell (EGC) activation was detected through quantitative real-time PCR (qRT-PCR), immunoblotting and immunohistology analysis. Fluorocitrate or genetic deletion of glial fibrillary acidic protein (GFAP)-positive glial-intrinsic myeloid differentiation factor 88 (Myd88) was used to inhibit EGC activation, and the effect of a high-fat diet on obesity was further investigated. The role of MYD88-dependent sensing of commensal products in adipocyte was observed to analyze the effect of obesity. Results A dietary shift from a normal chow diet to a high-fat diet in mice induced a transient early-phase emergence of a GFAP-positive EGC network in the lamina propria of the ileum, accompanied with an increase in glial-derived neurotrophic factor production. Inhibition of glial cell activity blocked this response. GFAP-positive glial Myd88 knockout mice gained less body weight after high-fat diet (HFD) feeding than littermate controls. In contrast, adipocyte deletion of Myd88 in mice had no effect on weight gain but instead exacerbated glucose intolerance. Furthermore, short-term fluorocitrate intervention during HFD feeding attenuated body weight gain. Conclusions Our findings indicate that EGCs are early responders to intestinal ecosystem changes and the GFAP-positive glial Myd88 signaling participates in regulating obesity.

A maternal high-fat/low-fiber diet impairs glucose tolerance and induces the formation of glycolytic muscle fibers in neonatal offspring.

In our previous study, the maternal high-fat/low-fiber (HF-LF) diet was suggested to induce metabolic disorders and placental dysfunction of the dam, but the effects of this diet on glucose metabolism of neonatal offspring remain largely unknown. Here, a neonatal pig model was used to evaluate the effects of maternal HF-LF diet during pregnancy on glucose tolerance, transition of skeletal muscle fiber types, and mitochondrial function in offspring. A total of 66 pregnant gilts (Guangdong Small-ear Spotted pig) at day 60 of gestation were randomly divided into two groups: control group (CON group; 2.86% crude fat, 9.37% crude fiber), and high-fat/low-fiber diet group (HF-LF group; 5.99% crude fat, 4.13% crude fiber). The maternal HF-LF diet was shown to impair the glucose tolerance of neonatal offspring, downregulate the protein level of slow-twitch fiber myosin heavy chain I (MyHC I), and upregulate the protein levels of fast-twitch fiber myosin heavy chain IIb (MyHC IIb) and IIx (MyHC IIx) in soleus muscle. Additionally, compared with the CON group, the HF-LF offspring showed inhibition of insulin signaling pathway and decrease in mitochondrial function in liver and soleus muscle. Maternal HF-LF diet during pregnancy impairs glucose tolerance, induces the formation of glycolytic muscle fibers, and decreases the hepatic and muscular mitochondrial function in neonatal piglets.

Associations of the Fecal Microbial Proteome Composition and Proneness to Diet-induced Obesity

Consumption of refined high-fat, low-fiber diets promotes development of obesity and its associated consequences. Although genetics play an important role in dictating susceptibility to such obesogenic diets, mice with nearly uniform genetics exhibit marked heterogeneity in their extent of obesity in response to such diets. This suggests non-genetic determinants play a role in diet-induced obesity. Hence, we sought to identify parameters that predict, and/or correlate with, development of obesity in response to an obesogenic diet. We assayed behavior, metabolic parameters, inflammatory markers/cytokines, microbiota composition, and the fecal metaproteome, in a cohort of mice (n = 50) prior to, and the 8 weeks following, administration of an obesogenic high-fat low-fiber diet. Neither behavioral testing nor quantitation of inflammatory markers broadly predicted severity of diet-induced obesity. Although, the small subset of mice that exhibited basal elevations in serum IL-6 (n = 5) were among the more obese mice in the cohort. While fecal microbiota composition changed markedly in response to the obesogenic diet, it lacked the ability to predict which mice were relative prone or resistant to obesity. In contrast, fecal metaproteome analysis revealed functional and taxonomic differences among the proteins associated with proneness to obesity. Targeted interrogation of microbiota composition data successfully validated the taxonomic differences seen in the metaproteome. Although future work will be needed to determine the breadth of applicability of these associations to other cohorts of animals and humans, this study nonetheless highlights the potential power of gut microbial proteins to predict and perhaps impact development of obesity.

Effect of Saccharomyces Boulardii Cell Wall Extracts on Colon Cancer Prevention in Male F344 Rats Treated with 1,2-Dimethylhydrazine

ABSTRACTThe effect of Saccharomyces boulardii cell wall extracts on colon cancer prevention in rats treated with 1,2-dimethylhydrazine was investigated. A crude insoluble glucan (0.5 and 1.0 mg/kg/day) and a crude mannoprotein extract (0.3 and 3.0 mg/kg/day) were administered in rats by gavage for 12 weeks along with a high fat low fiber diet whereupon rats were sacrificed and aberrant crypt foci (ACF) were counted in the colon. Moreover, NAD(P)H: quinone reductase (QR) and harmful fecal enzymes (β-glucosidase and β-glucuronidase) were quantified in the liver and in the caecum, respectively. Results showed a reduction in ACF counts, a decreased β-glucuronidase activity and an increased QR activity when rats were treated only with insoluble glucan. While these enzymatic modulations may be constituted one of the mechanisms that is responsible for the reduction of ACF counts observed, the reduction of ACF counts caused by insoluble glucan should be addressed, at least, as a biomarker of their cancer-prevention properties. To our knowledge, this is the first study demonstrated that crude cell wall extract obtained from S. boulardii could have a potential role in colon cancer prevention in vivo by revealing the potential implication of QR and β-glucuronidase modulation.

Impact of a High-Fat or High-Fiber Diet on Intestinal Microbiota and Metabolic Markers in a Pig Model.

To further elaborate interactions between nutrition, gut microbiota and host health, an animal model to simulate changes in microbial composition and activity due to dietary changes similar to those in humans is needed. Therefore, the impact of two different diets on cecal and colonic microbial gene copies and metabolic activity, organ development and biochemical parameters in blood serum was investigated using a pig model. Four pigs were either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for seven weeks, with both diets being isocaloric. A hypotrophic effect of the HF diet on digestive organs could be observed compared to the LF diet (p < 0.05). Higher gene copy numbers of Bacteroides (p < 0.05) and Enterobacteriaceae (p < 0.001) were present in intestinal contents of HF pigs, bifidobacteria were more abundant in LF pigs (p < 0.05). Concentrations of acetate and butyrate were higher in LF pigs (p < 0.05). Glucose was higher in HF pigs, while glutamic pyruvic transaminase (GPT) showed higher concentrations upon feeding the LF diet (p < 0.001). However, C-reactive protein (CRP) decreased with time in LF pigs (p < 0.05). In part, these findings correspond to those in humans, and are in support of the concept of using the pig as human model.

Intestinal Microbiota and Microbial Metabolites Are Changed in a Pig Model Fed a High-Fat/Low-Fiber or a Low-Fat/High-Fiber Diet.

The intestinal microbiota and its metabolites appear to be an important factor for gastrointestinal function and health. However, research is still needed to further elaborate potential relationships between nutrition, gut microbiota and host’s health by means of a suitable animal model. The present study examined the effect of two different diets on microbial composition and activity by using the pig as a model for humans. Eight pigs were equally allotted to two treatments, either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for 7 weeks. Feces were sampled at day 7 of every experimental week. Diet effects on fecal microbiota were assessed using quantitative real-time PCR, DNA fingerprinting and metaproteomics. Furthermore, fecal short-chain fatty acid (SCFA) profiles and ammonia concentrations were determined. Gene copy numbers of lactobacilli, bifidobacteria (P<0.001) and Faecalibacterium prausnitzii (P<0.05) were higher in the LF pigs, while Enterobacteriaceae were more abundant in the HF pigs (P<0.001). Higher numbers of proteins affiliated to Enterobacteriaceae were also present in the HF samples. Proteins for polysaccharide breakdown did almost exclusively originate from Prevotellaceae. Total and individual fecal SCFA concentrations were higher for pigs of the LF treatment (P<0.05), whereas fecal ammonia concentrations did not differ between treatments (P>0.05). Results provide evidence that beginning from the start of the experiment, the LF diet stimulated beneficial bacteria and SCFA production, especially butyrate (P<0.05), while the HF diet fostered those bacterial groups which have been associated with a negative impact on health conditions. These findings correspond to results in humans and might strengthen the hypothesis that the response of the porcine gut microbiota to a specific dietary modulation is in support of using the pig as suitable animal model for humans to assess diet-gut-microbiota interactions.Data are available via ProteomeXchange with identifier PXD003447.

Distribution of Risk Factors in Patients with Colorectal Cancer in Saudi Arabia

Objective: To identify the risk factors for Colorectal Cancer (CRC) at King AbdulAziz University Hospital (KAUH) in the western region of Saudi Arabia. Methods: Clinical, pathological and risk factors data of all patients with CRC managed at KAUH, over a 10 years period (1993-2002) were collected and analyzed retrospec-tively. Risk factors, were then correlated with sex and race (Saudis vs Non- Saudis). Results: Out of 90 patients evaluated, 5 were excluded because of incomplete data. Out of 85 patients, 45 (52.9%) patients were males, 40 (47.1%) females, 33 (38.8) Saudis and 52 (61.2%) were Non-Saudis. The Majority were Asians; 81 out of 85patients (95.3%) and4African (4.7%). Comparisons between males and females revealed no dif-ference for all the following risk factors; familial causes, polyps, Inflammatory bowel disease (IBD), High fat low fiber diet, Non steroidal anti inflammatory drugs (NSAIDS) use and Obesity. Comparisons between Saudis and Non-Saudis revealed no difference in all mentioned risk factors except for familial causes which was found higher among Saudis versus Non-Saudis (15.2% vs 1.9%, P = 0.031). Conclusions: Risk factors for CRC are present in this study population especially dietary habits and obesity. Fa-milial risk factors were higher among Saudis than Non Saudis. The relative high frequency of some risk factors calls for family screening and surveillance.

Effect of high‐fat and low‐fiber meals on the cell proliferation activity of colorectal mucosa

Normal healthy volunteers (n = 43) were divided into four groups that received diets providing low or high levels of dietary fat (33 or 96 g/day) and low or high levels of dietary fiber (6 and 41 g/day) for a period of five days. Proliferation was assessed with tritiated thymidine labeling of three rectal biopsies. After five days on the prescribed diets, the average thymidine labeling index (LI) of the group on the high fat-low fiber diet was only 25% higher than the average LI of the group on the low fat-high fiber diet, a difference that is not statistically significant. We conclude that a short-term increase in dietary fat and decrease in dietary fiber does not result in a large increase in cell proliferation rate.

Estrogens, breast cancer, and intestinal flora.

Epidemiologic evidence has linked diet to breast cancer, with the highest cancer rates observed in women who eat a high fat-low fiber diet. There is also substantial information, both clinical and experimental, that implicates estrogens in the etiology of breast cancer. A recent study from our laboratory has shown that diet influences levels of estrogens, and the main mechanism is metabolism of estrogens in the intestine. The intestinal microflora plays a key role in the enterohepatic circulation of estrogens by deconjugating bound estrogens that appear in the bile, thereby permitting the free hormones to be reabsorbed. By suppressing the microflora with antibiotic therapy, fecal estrogens increase and urinary estrogens decrease, changes indicating diminished intestinal reabsorption. A low fat-high fiber diet is associated with similar findings-high fecal estrogens and low urinary estrogens. It appears that the microflora plays a key role in the metabolism of female sex hormones.