scholarly journals Dietary fat and fiber impacts intestinal microbiome resilience to antibiotics and Clostridoides difficile infection in mice

2019 ◽  
Author(s):  
Keith Z. Hazleton ◽  
Casey G. Martin ◽  
Kathleen L. Arnolds ◽  
Nichole M. Nusbacher ◽  
Nancy Moreno-Huizar ◽  
...  
Keyword(s):  
Bile Acids ◽  
Dietary Fiber ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Intestinal Microbiome ◽  
High Fat ◽  
Low Fat ◽  
Effective Prevention ◽  
High Fiber ◽  
Fiber Diet

AbstractClostridoides difficile infection (CDI) is a leading cause of hospital-acquired diarrhea and there has been a steady increase in the number of new infections, emphasizing the importance of novel prevention strategies. Use of broad-spectrum antibiotics and disruption of the intestinal microbiome is one of the most important risk factors of CDI. We used a murine model of antibiotic-induced CDI to investigate the relative contributions of high dietary fat and low dietary fiber on disease pathogenesis. We found that high fat, but not low fiber resulted in increased mortality from CDI (HR 4.95) and increased levels of C. difficile toxin production compared to a regular low-fat/high-fiber mouse diet even though we did not observe a significant change in C. difficile carriage. The high-fat diet also increased levels of primary bile acids known to be germination factors for C. difficile spores. Mice fed low-fat/low-fiber diets did not show increased CDI pathogenesis, but did have a larger antibiotic-induced gut microbiome disturbance compared to mice fed a high-fiber diet, characterized by a greater decrease in alpha diversity. This microbiome disturbance was associated with a loss of secondary bile acids and short chain fatty acids, which are both microbial metabolic products previously shown to protect against CDI. These data suggest that a low-fiber diet contributes to antibiotic-induced dysbiosis, while a high-fat diet promotes CDI pathogenesis. These findings indicate that dietary interventions that increase fiber and decrease fat may be an effective prevention strategy for individuals at high risk of CDI.One Sentence SummaryHigh dietary fat promoted mortality in a mouse model of antibiotic-induced C. difficile infection and low dietary fiber caused higher microbiome disturbance upon broad-spectum antibiotic exposure, suggesting that diets low in fat and high in fiber may protect against C. difficile pathogenesis.

P063 A COMPREHENSIVE, MULTIOMIC DIET INTERVENTION STUDY COMPARING A LOW FAT, HIGH FIBER DIET TO AN IDEALIZED STANDARD AMERICAN DIET IN ULCERATIVE COLITIS PATIENTS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S8-S9
Author(s):  
Julia Fritsch ◽  
Alejandra Quintero ◽  
Judith Pignac-Kobinger ◽  
Luis Garces ◽  
Ana Santander ◽  
...  
Keyword(s):  
Quality Of Life ◽  
High Fat Diet ◽  
High Fat ◽  
Dietary Interventions ◽  
Low Fat ◽  
High Fiber ◽  
Fiber Diet ◽  
Omega 6 ◽  
High Fiber Diet

Abstract Background and Aims There is a lack of evidence-based dietary interventions in ulcerative colitis (UC) management. A diet high in fat and animal meat has been linked to an increased risk of UC. The aim of our study was to use a multilayered, multi-omic approach to comprehensively characterize the effect of a low fat, high fiber diet or a high fat diet in UC patients. Methods We enrolled patients with UC who were in remission or had mild disease with a flare within the last 18 months. We used a cross-over design in which patients received two dietary interventions: a low fat diet (LFD), containing 10% total calories from fat with an omega 6 to 3 ratio of below 3:1, and an idealized standard American diet (SAD), containing 35–40% total calories from fat with an omega 6 to 3 ratio of 20–30:1. Each diet was four weeks long with a two-week wash-out in between. The diet was catered and delivered to patients’ homes. Clinical symptoms, quality of life, and biochemical data were collected. Stool was collected for microbiome and metabolomic analyses. The primary endpoint was to determine adherence to a specified diet using catered meals; the secondary endpoint was to determine the clinical and subclinical effects of a low fat, high fiber diet or high fat diet in UC. Results Baseline diets varied widely but were generally lower in fiber as well as fruits and vegetables and higher in saturated fat than either of the study diets. There was a high rate of adherence to catered meals (SAD=86.68%, LFD=84.8%) with a 96.8% and 94.33% adherence to fat for SAD and LFD respectively. Patients that started in remission remained in remission (partial Mayo and sIBDQ). Following a LFD, patients saw a 20% improvement in their quality of life as measured by sIBDQ compared to their baseline. The effect of diet intervention on microbial diversity was reflected in the beta diversity with a significant increase in Faecalibacterium prausnitzii after LFD. CRP, sIBDQ, IL-6, and IL1β had a significant effect on overall gut microbiota composition as measured by Bray Curtis beta diversity (PERMANOVA)(P<0.007, P<0.001, P<0.021, P<0.048 respectively). The top taxa that contributes the most to this microbial variation from these clinical parameters was Faecalibacterium prausnitzii. Patients following a SAD had an increase in lauric acid, myristic acid, and N-oleoyl-L-phenylalanine with an increase in omega-6 metabolism pathways. Patients following a LFD had higher glycine, alanine, and phenyllactic acid with omega 3 metabolism pathways increased after LFD. Conclusions A low fat, high fiber diet is well tolerated and did not increase biochemical markers of inflammation. Catered meals and collection of microbiome, metabolome and biochemical data may allow early stratification of diet responders.

Acute changes in the response to peripheral leptin with alteration in the diet composition

2001 ◽  
Vol 280 (2) ◽  
pp. R504-R509 ◽  
Author(s):  
L. Lin ◽  
R. Martin ◽  
A. O. Schaffhauser ◽  
D. A. York
Keyword(s):  
Food Intake ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Corticosterone Level ◽  
Inhibitory Response ◽  
Leptin Resistance ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet ◽  
Alternative Diet

Dietary induced obesity in rodents is associated with a resistance to leptin. We have investigated the hypothesis that dietary fat per se alters the feeding response to peripheral leptin in rats that were fed either their habitual high- or low-fat diet or were naively exposed to the alternative diet. Osborne-Mendel rats were adapted to either high- or low-fat diet. Food-deprived rats were given either leptin (0.5 mg/kg body wt ip) or saline, after which they were provided with either their familiar diet or the alternative diet. Food intake of rats adapted and tested with the low-fat diet was reduced 4 h after leptin injection, whereas rats adapted and tested with a high-fat diet did not respond to leptin. Leptin was injected again 1 and 5 days after the high-fat diet-adapted rats were switched to the low-fat diet. Leptin reduced the food intake on both days. In contrast, when low-fat diet-adapted rats were switched to a high-fat diet, the leptin inhibitory response was present on day 1 but not observed on day 5. Peripheral injection of leptin increased serum corticosterone level and decreased hypothalamic neuropeptide Y mRNA expression in rats fed the low-fat but not the high-fat diet for 20 days. The data suggest that dietary fat itself, rather than obesity, may induce leptin resistance within a short time of exposure to a high-fat diet.

scholarly journals Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

2016 ◽  
Vol 310 (11) ◽  
pp. E886-E899 ◽  
Author(s):  
Pia Kiilerich ◽  
Lene Secher Myrmel ◽  
Even Fjære ◽  
Qin Hao ◽  
Floor Hugenholtz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Gut Microbiota ◽  
Dietary Fat ◽  
High Fat Diet ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet ◽  
Low Protein

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio.

0952 Intestinal microbiota, microbial metabolites and carcass traits are changed in a pig model fed a high-fat/low-fiber or a low-fat/high-fiber diet

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 458-458
Author(s):  
S. N. Heinritz ◽  
E. Weiss ◽  
M. Eklund ◽  
T. Aumiller ◽  
S. Messner ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Carcass Traits ◽  
Pig Model ◽  
Microbial Metabolites ◽  
High Fat ◽  
Low Fat ◽  
High Fiber ◽  
Fiber Diet ◽  
High Fiber Diet

scholarly journals The role of dietary fat in obesity-induced insulin resistance

2016 ◽  
Vol 311 (6) ◽  
pp. E989-E997 ◽  
Author(s):  
Denise E. Lackey ◽  
Raul G. Lazaro ◽  
Pingping Li ◽  
Andrew Johnson ◽  
Angelina Hernandez-Carretero ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Caloric Intake ◽  
High Fat ◽  
Low Fat ◽  
Feeding Method ◽  
Low Fat Diet ◽  
Obesity And Diabetes

Consumption of excess calories results in obesity and insulin resistance and has been intensively studied in mice and humans. The objective of this study was to determine the specific contribution of dietary fat rather than total caloric intake to the development of obesity-associated insulin resistance. We used an intragastric feeding method to overfeed excess calories from a low-fat diet (and an isocalorically matched high-fat diet) through a surgically implanted gastric feeding tube to generate obesity in wild-type mice followed by hyperinsulinemic-euglycemic clamp studies to assess the development of insulin resistance. We show that overfeeding a low-fat diet results in levels of obesity similar to high-fat diet feeding in mice. However, despite a similar body weight, obese high-fat diet-fed mice are more insulin resistant than mice fed an isocaloric low-fat diet. Therefore, increased proportion of calories from dietary fat further potentiates insulin resistance in the obese state. Furthermore, crossover diet studies revealed that reduction in dietary fat composition improves glucose tolerance in obesity. In the context of the current obesity and diabetes epidemic, it is particularly important to fully understand the role of dietary macronutrients in the potentiation and amelioration of disease.

scholarly journals A novel mechanism for gut barrier dysfunction by dietary fat: epithelial disruption by hydrophobic bile acids

2013 ◽  
Vol 304 (3) ◽  
pp. G227-G234 ◽  
Author(s):  
Lotta K. Stenman ◽  
Reetta Holma ◽  
Ariane Eggert ◽  
Riitta Korpela
Keyword(s):  
Bile Acids ◽  
Dietary Fat ◽  
Barrier Function ◽  
High Fat Diet ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Epithelial Integrity

Impairment of gut barrier is associated with a fat-rich diet, but mechanisms are unknown. We have earlier shown that dietary fat modifies fecal bile acids in mice, decreasing the proportion of ursodeoxycholic acid (UDCA) vs. deoxycholic acid (DCA). To clarify the potential role of bile acids in fat-induced barrier dysfunction, we here investigated how physiological concentrations of DCA and UDCA affect barrier function in mouse intestinal tissue. Bile acid experiments were conducted in vitro in Ussing chambers using 4- and 20-kDa FITC-labeled dextrans. Epithelial integrity and inflammation were assayed by histology and Western blot analysis for cyclooxygenase-2. LPS was studied in DCA-induced barrier dysfunction. Finally, we investigated in a 10-wk in vivo feeding trial in mice the barrier-disrupting effect of a diet containing 0.1% DCA. DCA disrupted epithelial integrity dose dependently at 1–3 mM, which correspond to physiological concentrations on a high-fat diet. Low-fat diet-related concentrations of DCA had no effect. In vivo, the DCA-containing diet increased intestinal permeability 1.5-fold compared with control ( P = 0.016). Hematoxylin-eosin staining showed a clear disruption of the epithelial barrier by 3 mM DCA in vitro. A short-term treatment by DCA did not increase cyclooxygenase-2 content in colon preparations. UDCA did not affect barrier function itself, but it ameliorated DCA-induced barrier disruption at a 0.6 mM concentration. LPS had no significant effect on barrier function at 0.5–4.5 μg/ml concentrations. We suggest a novel mechanism for barrier dysfunction on a high-fat diet involving the effect of hydrophobic luminal bile acids.

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

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0154329 ◽  
Author(s):  
Sonja N. Heinritz ◽  
Eva Weiss ◽  
Meike Eklund ◽  
Tobias Aumiller ◽  
Sandrine Louis ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Pig Model ◽  
Microbial Metabolites ◽  
High Fat ◽  
Low Fat ◽  
High Fiber ◽  
Fiber Diet ◽  
High Fiber Diet

Effect of low-fat, high-carbohydrate, high-fiber diet on fecal bile acids and neutral sterols

1988 ◽  
Vol 17 (4) ◽  
pp. 432-439 ◽  
Author(s):  
Bandaru S. Reddy ◽  
Althea Engle ◽  
Barbara Simi ◽  
Lynn T. O'Brien ◽  
R.James Barnard ◽  
...  
Keyword(s):  
Bile Acids ◽  
Low Fat ◽  
High Fiber ◽  
High Carbohydrate ◽  
Fecal Bile Acids ◽  
Fiber Diet ◽  
Neutral Sterols ◽  
High Fiber Diet

Intracerebroventricular infusions of 3-OHB and insulin in a rat model of dietary obesity

1988 ◽  
Vol 255 (6) ◽  
pp. R974-R981 ◽  
Author(s):  
K. Arase ◽  
J. S. Fisler ◽  
N. S. Shargill ◽  
D. A. York ◽  
G. A. Bray
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Third Ventricle ◽  
Sprague Dawley ◽  
High Fat ◽  
Low Fat ◽  
The Third ◽  
Intracerebroventricular Infusion

We examined the effect of dietary fat on the response to 3-hydroxybutyrate (3-OHB) and insulin infused chronically into the third ventricle in three strains of rats with differing susceptibility to obesity induced by a high-fat diet: Osborne-Mendel rats are most susceptible; Sprague-Dawley-rats are intermediate; and S 5B/Pl rats are most resistant. Ten days after implantation of cannulas into the third ventricle, rats were fed either a low-fat diet or a high-fat diet for 14 days. On day 7, osmotic minipumps were attached to the ventricular cannulas. 3-OHB infusions (3.6 mumol/24 h) reduced food intake and body weight in Sprague-Dawley and Osborne-Mendel rats eating either diet. The dietary fat-resistant S 5B/Pl rats did not respond to the intracerebroventricular infusion of 3-OHB. The infusion of insulin (10 mU/24 h) lowered food intake and body weight in animals eating the low-fat (high-carbohydrate) diet but not in animals eating the high-fat diet. Diet profoundly affects the response to intracerebroventricular infusions of insulin but is without effect on the response to 3-OHB.

scholarly journals Dietary fat and corticosterone levels are contributing factors to meal anticipation

2016 ◽  
Vol 310 (8) ◽  
pp. R711-R723 ◽  
Author(s):  
Sara Namvar ◽  
Amy Gyte ◽  
Mark Denn ◽  
Brendan Leighton ◽  
Hugh D. Piggins
Keyword(s):  
Dietary Fat ◽  
High Fat Diet ◽  
Fat Content ◽  
High Fat ◽  
Contributing Factors ◽  
Low Fat ◽  
Restricted Access ◽  
Fos Expression ◽  
Fat Feeding

Daily restricted access to food leads to the development of food anticipatory activity and metabolism, which depends upon an as yet unidentified food-entrainable oscillator(s). A premeal anticipatory peak in circulating hormones, including corticosterone is also elicited by daily restricted feeding. High-fat feeding is associated with elevated levels of corticosterone with disrupted circadian rhythms and a failure to develop robust meal anticipation. It is not clear whether the disrupted corticosterone rhythm, resulting from high-fat feeding contributes to attenuated meal anticipation in high-fat fed rats. Our aim was to better characterize meal anticipation in rats fed a low- or high-fat diet, and to better understand the role of corticosterone in this process. To this end, we utilized behavioral observations, hypothalamic c-Fos expression, and indirect calorimetry to assess meal entrainment. We also used the glucocorticoid receptor antagonist, RU486, to dissect out the role of corticosterone in meal anticipation in rats given daily access to a meal with different fat content. Restricted access to a low-fat diet led to robust meal anticipation, as well as entrainment of hypothalamic c-Fos expression, metabolism, and circulating corticosterone. These measures were significantly attenuated in response to a high-fat diet, and animals on this diet exhibited a postanticipatory rise in corticosterone. Interestingly, antagonism of glucocorticoid activity using RU486 attenuated meal anticipation in low-fat fed rats, but promoted meal anticipation in high-fat-fed rats. These findings suggest an important role for corticosterone in the regulation of meal anticipation in a manner dependent upon dietary fat content.

Sign in / Sign up

Export Citation Format

Share Document