High-fat diet disrupts microbiome composition, causes inflammation in heart failure

A diet high in omega-6 fatty acids, coupled with aging, may alter gut microbes and cause an inflamed state in heart failure, according to a new study published by researchers from the University of Alabama at Birmingham (UAB) in the FASEB Journal.

Ganesh Halade, PhD, assistant professor in the UAB Department of Medicine, and lead researcher, examined calorie-dense obesogenic diets (OBD) as a prime risk factor for cardiovascular disease in aging. Increasing age combined with dietary changes can affect the interaction of intestinal microbiota, influencing the immune system, and potentially leading to chronic inflammation, according to the study, which was announced formally by the university last week. How age and a calorie-enriched OBD interact with microbial flora and impact leukocyte profiling is still under investigation, researchers said.

The research team studied mice to determine whether OBD in young and aging mice alters the gut microbiome composition and the splenic leukocyte profile in acute heart failure. Young mice, two months old, and aging mice, 18 months old, were supplemented with either a standard diet (STD) of about 4 percent safflower oil, or an OBD of about 10 percent safflower oil. After continuing the diet for two months, researchers subjected the mice to coronary artery ligation to induce myocardial infarction.

Fecal samples were collected pre- and post-dietary intervention, and the microbiocidal flora were analyzed genetic sequencing and microbial ecology informatics, according to the study.

Researchers found both the STD and OBD in aging mice resulting in an expansion of the genus Allobaculum in the fecal microbiota. In addition, they found a pathologic change in the neutrophil-lymphocyte ratio in aging mice, when compared to the younger mice. They found a calorie-enriched OBD dysregulated splenic leukocytes by decreasing immune response. OBD programmed neutrophil swarming with an increase in isoprostanoid levels, with dysregulation of lipoxygenases, cytokines, and metabolite-sensing receptor expression, the researchers said.

Calorie-dense OBD in aging mice disrupted the composition of the gut microbiome, which correlates with the development of integrative and system-wide nonrevolving inflammation in acute heart failure, the researchers concluded.

“Thus, the data strongly indicate that the obesity-generating diet develops an inflammatory microenvironment, even in young mice, that amplifies with aging,” Halade said. “This study highlights that diet and age are critical factors that have differential impact with age, and it highlights the spleen and heart as an inter-organ communication system with the immune defense system.”