Introduction We present the following tri-factorial hypothesis:

1. All members of the Chlamydiaceae have evolved primarily as commensals of the digestive tract of their host(s) with fecal-oral transmission (FOT) as the principal route of dissemination to new hosts. In communities where fecal-oral transmission is reduced (e.g., via global sanitation), the occurrence of chlamydiae in the digestive tract of their host is reduced.2. Chlamydia trachomatis is a commensal microorganism of the human gastro-intestinal (GI) tract, and an opportunistic pathogen in the genital and respiratory tracts, and the conjunctiva. Under conditions of reduced FOT, direct contact (e.g., sexual) is the primary mode of transmission.

3. C. trachomatis is efficiently transmitted to the GI tract of new hosts via oral sex. The practice of oral sex has ‘reintroduced’ C. trachomatis to the human GI tract in communities where FOT was previously reduced.

Methods Circumstantial, historical and recent evidence from humans and animals that support the hypothesis is reviewed. Imaging of mCherry expressing Chlamydia muridarum in the murine GI tract was obtained.

Results and Conclusion: Tenets 1 and 2 imply a paradigm shift to reflect a revision of the status of C. trachomatis from that of a principal pathogen to that of a commensal organism that causes opportunistic infection at mucosal epithelia other than its preferred GI site. High frequency on/off switching of the expression of autotransported polymorphic membrane proteins, the unique properties of peptidoglycan and lipo-oligosaccharide, and observed extruded inclusions in the GI tract of C. muridarum-infected mice may facilitate chlamydial survival and colonisation of the GI tract.Tenet 3 implies that orally inoculated chlamydiae that survive in and colonise the GI tract, may reach the rectum and chronically, or episodically, infect the female genital tract eventually causing/contributing to tubal pathology and infertility. The global hypothesis therefore raises the provocative question: does oral sex cause or contribute to female infertility?