It has been previously reported that clinical interventions on the gut microbiota constitute a new approach for preventing side effects of bone marrow transplant. Little is known regarding the role of environmental factors such as microbiota in transplant rejection. A recent study, led by Dr. Maria-Luisa Alegre from the Department of Medicine at University of Chicago (Illinois, USA), has found that the microbiota may play an important role in the body’s ability to accept transplanted organs.
Organs colonized with bacteria, such as the skin, lungs, and intestines, have poorer transplant outcomes than organs considered sterile such as the heart and kidney. One hypothesis suggested to explain this fact is that commensal microbiota colonizing these organs may have a role in alloimmunity. To assess this hypothesis, Yuk Man Lei and colleagues treated both donor and recipient mice with a daily gavage of antibiotics for 10 days before performing skin transplants. The researchers demonstrated that skin grafts in mice treated with pre-transplantation antibiotics survived roughly twice as long as those in mice that did not receive antibiotics (with a mean survival time of 53 versus 27 days). In particular, antibiotic-pretreated mice had a relative expansion of Lactobacillus in the faeces and a reduction of Clostridiales both in the faeces and on the skin. Besides this, skin grafts in germ-free (GF) mice (raised in a sterile environment) also survived longer when compared with those in mice with a specific pathogen-free microbiota transplanted in a sterile manner.
Antibiotic pretreatment not only affected graft survival, but also decreased specific immune responses against the skin graft. Increased graft survival correlated with reduced type I interferon (IFN) signalling in dendritic cells from skin-draining lymph nodes, and decreased priming of alloreactive T cells.
It has also been found that if GF mice were given faecal microbiota transfers from conventional, untreated mice, they rejected the skin grafts more quickly. However, if GF mice were dosed with microbes from mice that had been treated with antibiotics, they rejected the skin grafts slowly, which demonstrates distinct effects on skin graft outcome depending on gut microbiota composition. In addition, the effects were not attributable to antibiotics merely reducing the quantity of bacteria. “Antibiotic pretreatment changed the composition of the microbiota, but not the overall bacterial load. So it is not the quantity of bacteria that makes the difference, it is the bacterial community,” says Dr. Alegre.
Changing the microbiota also affected the outcomes of heart transplant; hearts transplanted into conventional mice pretreated with antibiotics survived longer as well.
All together, these results suggest that gut microbiota composition may affect the outcome of organ transplants. A better understanding of the role microbes play in priming or suppressing the immune response to a transplanted organ could lead surgeons to target microbiota composition as a potential way to improve transplant outcomes.
Lei YM, Chen L, Wang Y, et al. The composition of the microbiota modulates allograft rejection. J Clin Invest. 2016; 126(7):2736-44. doi:10.1172/JCI85295.