ABOVE: Gut bacteria partly explain why obese mice had worse outcomes than lean individuals after bone marrow transplantation. 


The paper
L.T. Khuat et al., “Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation,” Sci Trans Med, 12:eaay7713, 2020.

Bone marrow transplants are widely used to treat certain cancers and blood diseases, but these procedures run the risk of a serious complication called graft-versus-host disease (GVHD). This immune disorder occurs when donor T cells recognize the recipient’s body as foreign, triggering inflammatory immune responses that damage the patient’s organs and can cause death. Previous studies have shown that obesity can influence immune responses, but its effects on GVHD are poorly understood. 

To interrogate the effect of obesity on bone marrow transplant outcomes, UC Davis Health immunologist William Murphy and his team used a donor-recipient mouse strain combination in which transplantation usually causes GVHD in the form of scaly skin and hair loss. In lean recipients, the transplant caused skin symptoms and all of the mice survived, as expected. In contrast, most mice with diet-induced obesity died within weeks from severe damage to the gut epithelial lining associated with greatly elevated levels of inflammatory cytokines, an outcome that resembled acute GVHD. “That was a shock,” says Murphy. “Just by making [the mice] fat . . . we got markedly different outcomes.”

The gut lining of lean (left) and obese (right) mice after bone marrow transplantation show differences in cell size, type, and architecture.

In humans, the researchers found that obese bone marrow recipients had higher levels of a GVHD biomarker, more-severe gut damage, and lower survival than healthy-weight patients. Obese mice and humans both had lower gut bacterial diversity than their lean counterparts and lower levels of bacteria associated with good GVHD outcomes. When the team gave obese mice antibiotics before transplantation, survival improved by about 50 percent, suggesting that obesity-induced changes to gut bacteria affect GVHD severity. But “while the microbiome definitely is playing a role, it’s not the sole cause,” says Murphy.

“It’s nice work,” says Anna Staffas, a cancer researcher at the University of Gothenburg in Sweden who was not involved with the study. The results, she adds, “need to be validated in larger cohorts to see if the same conclusions can be drawn for humans.”