A gut feeling: How can gastrointestinal bacterial infections alter female reproductive tract immunity and control of sexually transmitted infections

Sexually transmitted infections (STIs) are highly prevalent amongst women in low- and middle-income countries, where they have a devastating impact on women's health and places financial strain on health care systems. Importantly, other infections are also common in these regions, making co-infections likely to occur. Previous studies have shown that gastrointestinal (GI) infections can change immunity and control of unrelated infections at other biological compartments. Bacterial infections of the GI system are common in regions with high rates of STIs, and can cause systemic inflammation. However, little is known about how GI bacterial infections affect immunity in the female reproductive tract (FRT) and susceptibility to infections.

We have previously used mouse infection models to that helminth infections can indirectly change FRT immunity and this had a detrimental effect on STI disease. In this study, I will investigate the effects of a remote GI bacterial infection on FRT immunity, how this affects control of common STIs, as well as the effects on fertility. The proposed research will build an important foundation for future human studies. A better understanding of the indirect influences on FRT health, will significantly contribute to STI prevention and treatment in the future.

Sexually transmitted infections (STIs) have a devastating impact on female health in low- and middle-income regions such as sub-Saharan Africa, where other infections are also prevalent. Therefore, it is important to understand how such infections at distal biological sites, can affect female reproductive health. Known microbial and immune influences between the gastrointestinal (GI) tract and the lung demonstrates how important the distal effects of GI infection on other mucosal sites can be. However, our understanding of the distal influences of GI infections on the female reproductive system is limited. Bacterial infections in STI-endemic regions are common, often highly pathogenic and cause systemic inflammation. The distal effects of GI bacterial infections on the FRT is under-studied and needs to be addressed.

We have previously discovered how a prior helminth infection that does not colonise the FRT, alters immunity in the vagina and exacerbates subsequent immunopathology to a common viral STI. This demonstrates that infections at distal sites can affect FRT susceptibility to infection and disease. In this study, I will further explore this underappreciated axis of influence by testing how a GI bacterial infection distally influences female reproductive immunity and susceptibility to common pathogenic STIs, as well as the effects on fertility.

I will use complementary immunological, biochemical, and microbiological techniques, to dissect underlying mechanisms of this axis of influence. This work will provide an important foundation for future clinical studies into how common GI bacterial infections distally influence FRT immunity and susceptibility to STIs.