A High-Fat/High-Protein, Atkins-Type Diet Exacerbates Clostridioides (Clostridium) difficile Infection in Mice, whereas a High-Carbohydrate Diet Protects

ABSTRACT Clostridioides difficile (formerly Clostridium difficile) infection (CDI) can result from the disruption of the resident gut microbiota. Western diets and popular weight-loss diets drive large changes in the gut microbiome; however, the literature is conflicted with regard to the effect of diet on CDI. Using the hypervirulent strain C. difficile R20291 (RT027) in a mouse model of antibiotic-induced CDI, we assessed disease outcome and microbial community dynamics in mice fed two high-fat diets in comparison with a high-carbohydrate diet and a standard rodent diet. The two high-fat diets exacerbated CDI, with a high-fat/high-protein, Atkins-like diet leading to severe CDI and 100% mortality and a high-fat/low-protein, medium-chain-triglyceride (MCT)-like diet inducing highly variable CDI outcomes. In contrast, mice fed a high-carbohydrate diet were protected from CDI, despite the high levels of refined carbohydrate and low levels of fiber in the diet. A total of 28 members of the Lachnospiraceae and Ruminococcaceae decreased in abundance due to diet and/or antibiotic treatment; these organisms may compete with C. difficile for amino acids and protect healthy animals from CDI in the absence of antibiotics. Together, these data suggest that antibiotic treatment might lead to loss of C. difficile competitors and create a favorable environment for C. difficile proliferation and virulence with effects that are intensified by high-fat/high-protein diets; in contrast, high-carbohydrate diets might be protective regardless of the source of carbohydrate or of antibiotic-driven loss of C. difficile competitors. IMPORTANCE The role of Western and weight-loss diets with extreme macronutrient composition in the risk and progression of CDI is poorly understood. In a longitudinal study, we showed that a high-fat/high-protein, Atkins-type diet greatly exacerbated antibiotic-induced CDI, whereas a high-carbohydrate diet protected, despite the high monosaccharide and starch content. Our study results, therefore, suggest that popular high-fat/high-protein weight-loss diets may enhance CDI risk during antibiotic treatment, possibly due to the synergistic effects of a loss of the microorganisms that normally inhibit C. difficile overgrowth and an abundance of amino acids that promote C. difficile overgrowth. In contrast, a high-carbohydrate diet might be protective, despite reports on the recent evolution of enhanced carbohydrate metabolism in C. difficile.

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A high-fat/high-protein, Atkins-type diet exacerbates Clostridioides (Clostridium) difficile infection in mice, whereas a high-carbohydrate diet protects

10.1101/834903 ◽

2019 ◽

Author(s):

Chrisabelle C. Mefferd ◽

Shrikant S. Bhute ◽

Jacqueline R. Phan ◽

Jacob V. Villarama ◽

Dung M. Do ◽

...

Keyword(s):

Clostridium Difficile ◽

Antibiotic Treatment ◽

Community Dynamics ◽

High Carbohydrate Diet ◽

High Protein ◽

High Fat ◽

Carbohydrate Diet ◽

High Carbohydrate ◽

High Fat Diets ◽

Fat Diets

AbstractClostridioides difficile (formerly Clostridium difficile) infection (CDI) can result from the disruption of the resident gut microbiota. Western diets and popular weight-loss diets drive large changes in the gut microbiome; however, the literature is conflicted with regard to the effect of diet on CDI. Using the hypervirulent strain C. difficile R20291 (RT027) in a mouse model of antibiotic-induced CDI, we assessed disease outcome and microbial community dynamics in mice fed two high-fat diets in comparison with a high-carbohydrate diet and a standard rodent diet. The two high-fat diets exacerbated CDI, with a high-fat/high-protein, Atkins-like diet leading to severe CDI and 100% mortality, and a high-fat/low-protein, medium-chain triglyceride (MCT)-like diet inducing highly variable CDI outcomes. In contrast, mice fed a high-carbohydrate diet were protected from CDI, despite high refined carbohydrate and low fiber content. 28 members of the Lachnospiraceae and Ruminococcaceae decreased in abundance due to diet and/or antibiotic treatment; these organisms may compete with C. difficile for amino acids and protect healthy animals from CDI in the absence of antibiotics. Together, these data suggest that antibiotic treatment might lead to loss of C. difficile competitors and create a favorable environment for C. difficile proliferation and virulence that is intensified by high-fat/high-protein diets; in contrast, high-carbohydrate diets might be protective regardless of the source of carbohydrate.

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Linoleate-Rich High-Fat Diet Decreases Mortality in Hypertensive Heart Failure Rats Compared With Lard and Low-Fat Diets

Hypertension ◽

10.1161/hypertensionaha.108.114264 ◽

2008 ◽

Vol 52 (3) ◽

pp. 549-555 ◽

Cited By ~ 44

Author(s):

Adam J. Chicco ◽

Genevieve C. Sparagna ◽

Sylvia A. McCune ◽

Christopher A. Johnson ◽

Robert C. Murphy ◽

...

Keyword(s):

Heart Failure ◽

Fatty Acid ◽

High Fat Diet ◽

Hypertensive Heart Disease ◽

High Carbohydrate Diet ◽

High Fat ◽

Carbohydrate Diet ◽

High Carbohydrate ◽

High Fat Diets ◽

Fat Diets

Recent studies indicate that high-fat diets may attenuate cardiac hypertrophy and contractile dysfunction in chronic hypertension. However, it is unclear whether consuming a high-fat diet improves prognosis in aged individuals with advanced hypertensive heart disease or the extent to which differences in its fatty acid composition modulate its effects in this setting. In this study, aged spontaneously hypertensive heart failure rats were administered a standard high-carbohydrate diet or high-fat diet (42% of kilocalories) supplemented with high-linoleate safflower oil or lard until death to determine their effects on disease progression and mortality. Both high-fat diets attenuated cardiac hypertrophy, left ventricular chamber dilation, and systolic dysfunction observed in rats consuming the high-carbohydrate diet. However, the lard diet significantly hastened heart failure mortality compared with the high-carbohydrate diet, whereas the linoleate diet significantly delayed mortality. Both high-fat diets elicited changes in the myocardial fatty acid profile, but neither had any effect on thromboxane excretion or blood pressure. The prosurvival effect of the linoleate diet was associated with a greater myocardial content and linoleate-enrichment of cardiolipin, an essential mitochondrial phospholipid known to be deficient in the failing heart. This study demonstrates that, despite having favorable effects on cardiac morphology and function in hypertension, a high-fat diet may accelerate or attenuate mortality in advanced hypertensive heart disease depending on its fatty acid composition. The precise mechanisms responsible for the divergent effects of the lard and linoleate-enriched diets merit further investigation but may involve diet-induced changes in the content and/or composition of cardiolipin in the heart.

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Transient hypophagia in rats switched from high-fat diets with different fatty-acid pattern to a high-carbohydrate diet

Appetite ◽

10.1006/appe.1999.0303 ◽

2000 ◽

Vol 34 (2) ◽

pp. 137-145 ◽

Cited By ~ 7

Author(s):

E. Del Prete ◽

T.A. Lutz ◽

E. Scharrer

Keyword(s):

Fatty Acid ◽

Fatty Acid Pattern ◽

High Carbohydrate Diet ◽

High Fat ◽

Carbohydrate Diet ◽

High Carbohydrate ◽

High Fat Diets ◽

Fat Diets

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Biochemical aspects of malabsorption in marasmus: effect of dietary rehabilitation

British Journal Of Nutrition ◽

10.1079/bjn19850143 ◽

1985 ◽

Vol 54 (3) ◽

pp. 567-575 ◽

Cited By ~ 3

Author(s):

H. C. Mehta ◽

A. S. Saini ◽

Harjit Singh ◽

P. S. Dhatt

Keyword(s):

Total Energy ◽

High Fat Diet ◽

High Protein Diet ◽

High Carbohydrate Diet ◽

High Protein ◽

Protein Diet ◽

Duodenal Juice ◽

High Fat ◽

Carbohydrate Diet ◽

High Carbohydrate

1. Sixty marasmic children were investigated for the absorption of xylose, proteins and fats. Their duodenal juice samples were also analysed for bile salts and microflora.2. The marasmic children were then studied in three groups of twenty by allocating them to three different dietary schedules: a high-protein diet (30% of the total energy from protein), a high-fat diet (40% of the total energy from fat) and a high-carbohydrate diet (70% of the total energy from carbohydrate) for 2 weeks and the previous measurements repeated.3. Whereas the high-fat diet resulted in improved fat absorption, along with an increase in total and conjugated bile acids, and the high-carbohydrate diet led to improved xylose absorption, the diet rich in protein resulted in an improvement in the absorption of all three dietary ingredients. It appears that a high-protein diet improves the overall absorption process by improving the intestinal environment as a whole, while high-carbohydrate and high-fat diets bring about adaptive changes related to the respective absorptive processes.

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