CDI was exacerbated by two high fat diets: an Atkins like high fat/protein diet that lead to severe CDI and 100% mortality; and a high fat-low protein MCT like diet that induced variable outcomes; this was hypothesised to possibly be due to the synergistic effects of a loss of the organisms that would typically inhibit C. diff overgrowth and an abundance of amino acids that promote overgrowth.
Mice that were fed a high carb diet were found to be protected against the symptoms of CDI despite the insulin content of the diet being low. The major sources of carbs in this diet were 43.5% corn starch, 14.4% maltodextrin, and 11% sucrose which would not be expected to improve gut health; the apparent protective effect of this diet was hypothesised to possibly be due to the low protein and/or fat content rather than the protective effects of the carbs.
“Every day we are learning more about the human microbiome and its importance in human health,” said Brain Hedlund, co-author and UNLV microbiologist. “The gut microbiome is strongly affected by diet, but the C. diff research community hasn’t come to a consensus yet on the effects of diet on its risk or severity. Our study helps address this by testing several diets with very different macronutrient content. That is, the balance of dietary carbohydrate, protein, and fat were very different.”
Groups of 5 mice were fed diets that differed in macronutrient composition: standard lab control diet; high carb diet; high fat/protein diet; and a high fat low protein diet; morbidity and mortality were examined throughout the study. Animal fed the control diet developed mild CDI signs but recovered; mean time of CDI onset was as 2.8 ± 0.4 days with a mean recovery time of 4.8 ± 0.4 days.
Only two of the mice on the high carb diet display mild symptoms and rapidly recovered with a mean CDI onset of 2.0 ± 1.8 days, and mean recovery of 3.0 ± 1.3 days. Mice on the high fat low protein diet displayed CDI symptom onset heterogeneity; 2 developed severe CDI and became moribund, and 3 developed mild to moderate signs similar to those on a standard diet and recovered within one week. Mean onest was 3.2 ±0.4 days with a mean recovery of 6.0 ± 0.0 days.
In the high fat/protein diet group all of the animals developed severe signs of CDI and all were euthanized within 4 days following challenge with C. diff; the mean onest was 1.6 ± 0.5 days.
There were differences in evenness, richness and shannon diversity between the diet groups after the animals were fed experimental diets for 10 days, those on the standard and high fat/low protein diets experienced most alpha diversity metrics returning to diet acclimated states within one month post challenge.
Findings suggest that diet may promote microbial groups that can be protective even after antibiotic depletion; for an infection to flourish “you might need this combination of wiping out C. diff competitors with antibiotics and then a diet that promotes overgrowth and disease.”
“Lots of papers say that lower microbial activity diversity is always a bad thing, but in this case, it had the best disease outcome,” says biochemist and co-author Ernesto Abel-Santos, who also cautions that a high carb diet may lead to animals being asymptomatic carriers that can spread infection to other subjects.
“Extreme diets are becoming very popular but we do not know the long-term effects on human health and specifically on the health of the human gut flora,” Abel-Santos said. “We have to look at humans to see if it correlates.”
