Microbiome Taxonomic and Functional Differences in C3H/HeJ Mice Fed a Long-Term High-Fat Diet with Beef Protein ±...

Studies have suggested that alkalinized foods may reduce the effects of the acidogenic Western diet in promoting obesity, metabolic syndrome, type 2 diabetes, cancer, and coronary heart disease. Indeed, a recent study in mice fed a high-fat diet containing dietary beef supplemented with ammonium hydroxide showed improvement in a suite of metabolic outcomes. However, the effects of dietary protein ammonium supplementation on the microbiome remain unknown. In this study, the effects of ammonium supplementation on beef protein towards microbiome taxa and function in a high-fat diet were analyzed. Fecal microbiomes were characterized using a shotgun metagenomic approach for 16-month-old male and female mice after long-term diet treatments. The results for ammoniated diets showed that several bacteria known to be associated with health benefits increased significantly, including Romboutsia, Oscillospiraceae, and Lactococcus cremoris. The beneficial mucin-degrader Akkermansia was especially abundant, with a high prevalence (~86%) in females. Concurrently, the phyla Actinomycetota (Actinobacteria) and Bacteroidota (Bacteroidetes) were significantly reduced. While sex was a confounding factor affecting microbiome responses to ammonium supplementation in dietary protein, it is worth noting that several putatively beneficial microbiome functions increased with ammonium supplementation, such as glycine betaine transport, xenobiotic detoxification, enhanced defense, and others. Conversely, many disease-associated microbiome functions reduced. Importantly, modifying protein pH alone via ammonium supplementation induced beneficial microbiota changes. Taken together, these results suggest that ammonium-supplemented proteins may mediate some negative microbiome-associated effects of high-fat/Western diets.