The Effects of Biological Sex on Sepsis Treatments in Animal Models: A Systematic Review and a Narrative Elaboration on Sex- and Gender-Dependent Differences in Sepsis

Abstract

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Long-distance relationships - regulation of systemic host defense against infections by the gut microbiota

“…For example, sex-based differences in gut microbiota composition have been shown to impact systemic immunity in diseases like diabetes 151,152 . In mice, sexual dimorphism is associated with differences in protection against sepsis, yet the mechanisms underlying this remain unexplored including a potential role for sex-based differences in the microbiota 153 . Lastly, our understanding of microbiota-immune interactions to date has been very bacteria-centric, and yet there is emerging data that other kingdoms of commensal microbes have a powerful impact on systemic immunity and host defense.…”

Sex differences associate with late microbiome alterations after murine surgical sepsis

“…Regardless, our results may help to better explain sex differences in postsepsis ICU survival given that females may have better survival compared with males. [8][9][10][11] These unique sex-related changes may be imparted on the host microbiota by the impact of sepsis and chronic stress. Such changes may lead to a chronic inflammatory state seen in PICS.…”

“…In fact, one study demonstrated that, in patients younger than 90 years, women had significantly decreased 1-year mortality compared with males 10 . Regardless, it is clear that females and males respond differently to infection 8–10 . Future successful interventions for sepsis will need to use personalized/precision medical therapies, which will require a better understanding of the differences in host response due to severe infection.…”

“…8,9 In fact, it is now recognized that "[a] better understanding of sex-and gender-dependent differences may serve to increase translational research success." 8 Although there is still significant debate as to whether females have improved outcomes after sepsis, 8,9 studies indicate that females are less likely to have postsepsis morbidity and mortality, even after menopause. 10,11 In fact, one study demonstrated that, in patients younger than 90 years, women had significantly decreased 1-year mortality compared with males.…”

“…10 Regardless, it is clear that females and males respond differently to infection. [8][9][10] Future successful interventions for sepsis will need to use personalized/ precision medical therapies, which will require a better understanding of the differences in host response due to severe infection.…”