How chronic intestinal inflammation can affect the heart

A recent study published in Circulation Research reveals that chronic intestinal inflammation can impact the heart via alterations in gut microbiota and immune cells. This finding suggests a possible therapeutic target for decreasing cardiovascular risk in patients with inflammatory bowel disease (IBD). The research, conducted using a chronic colitis mouse model, demonstrated that inflammation-associated gut microbiota imbalance (dysbiosis) contributes causally to cardiac hypertrophy (enlargement of the heart) and dysfunction in mice.

Mitochondria, organelles responsible for generating chemical energy in cells, are affected by this process.

Cardiovascular disease is a major cause of illness and death worldwide, and individuals with IBD, which encompasses chronic inflammatory conditions of the digestive tract, face a higher risk of heart complications. IBD is also linked to changes in the gut microbiota, the diverse community of microorganisms residing in the intestine, although the exact mechanisms linking these changes to heart issues have remained ambiguous.

By transferring gut microbiota from colitis-afflicted mice to healthy subjects, researchers observed alterations in immune cell metabolism and cardiac remodeling, indicating that shifts in gut microbes can indeed influence the heart. The study identified lipopolysaccharide (LPS), a bacterial component produced under disrupted intestinal conditions, as a key connection between the gut and heart.

Elevated LPS stimulates immune cells to produce GBP1, a protein that promotes their migration to the heart, contributing to abnormal enlargement and impaired function.

Moreover, GBP1, found in exosomes—tiny packages released by cells that carry biological signals—was observed to accumulate in heart cells during colitis, further exacerbating heart enlargement. The findings have broader implications for infection-associated cardiac injury, as many pathogens stimulate GBP family proteins, which although crucial for antimicrobial responses during infections, excessive or dysregulated activation can inadvertently lead to cardiac dysfunction.

The research was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health.