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.

From Nursery to Nursing Home: Emerging Concepts in Clostridioides difficile Pathogenesis

“…Because of C. difficile's ability to ferment amino acids as a nutrient source, dietary protein may also play a role in C. difficile pathogenesis. A recent study found that a high-fat/high-protein diet intensified C. difficile proliferation and virulence in a mouse model of infection (117). This study also supported the protective role of a high-carbohydrate diet.…”

Lipid Species in the GI Tract are Increased by the Commensal Fungus Candida albicans and Decrease the Virulence of Clostridioides difficile

“…Other results have shown that feeding a high-fat diet coincident with antibiotic treatment increases susceptibility to CDI [76,77]. The regimen used in our studies was distinct from those previously described.…”

The gut microbiome and its potential role in paradoxical anaerobism in pupfishes of the Mojave Desert

“…Pupfish were either left untreated ( n = 12) or exposed ( n = 12) to a cocktail of kanamycin (400 μg • ml − 1 ), gentamicin (35 μg • ml − 1 ), colistin (850 IU • ml − 1 ), metronidazole (215 μg • ml − 1 ), and vancomycin (45 μg • ml − 1 ) for 48 h prior to oxygen consumption measurement. This combination of broad-spectrum antibiotics acting on protein synthesis (kanamycin and gentamicin), cell membrane integrity (colistin), DNA synthesis (metronidazole) and peptidoglycan synthesis (vancomycin) is often used to deplete the mouse gut microbial community to study Clostridioides difficile infections and is highly effective [ 28 ].…”