Microgenderome: An Important Variable for Developing Therapeutic Strategies?

Ravichandra Vemuri, Rohit Gundamaraju

School of Health Sciences, University of Tasmania, Launceston,Tasmania 7248 , AustraliaAustralia

DOI: https://doi.org/10.17140/goj-3-e005 · Published 2018-12-06 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2018 The Author(s)

Also available as PDF (figures and tables appear in the PDF).

OpenJournal Editorial Microgenderome: An Important Variable for Developing Therapeutic Strategies?

* Ravichandra Vemuri, BPharm; Rohit Gundamaraju, MPharm* School of Health Sciences, University of Tasmania, Launceston,Tasmania 7248, Australia * *Corresponding author Rohit Gundamaraju, MPharm School of Health Sciences, University of Tasmania, Launceston,Tasmania 7248, Australia; E-mail: rohit.gundamaraju@utas.edu.au Article information th th th th Received: October 16 , 2018; Revised: December 5 , 2018; Accepted: December 6 , 2018; Published: December 6 , 2018 Cite this article Vemuri R, Gundamaraju R. Microgenderome: An important variable for developing therapeutic strategies? Gastro Open J. 2018; 3(1): e4-e5. doi: 10.17140/GOJ-3-e005 close association of microbiota in human health continues ta, sex-hormones and immune responses of the host (Figure 1). to emerge. Microbiota has been implicated in autoimmune Growing body of evidence suggest that gender-bias observed in A disorders such as type I diabetes mellitus, inflammatory bowel di- numerous diseases is numerous diseases was host-intrinsic factor sease, rheumatoid arthritis and multiple sclerosis.1 This is pointing adding to severity and susceptibility of the disease. In patients with out that early-life microbial exposure could be linked to later-life Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, gut micro- susceptibility to immune-mediated disorders. From the experimen- biota played a dual role in protection and exacerbation of disease.2 tal models related to autoimmune disorders, it is known that tis- This cross-sectional report and faecal microbiota data in 274 pa- sue injury is prevented by alteration in microbiota or in germ-free tients revealed sex-specific interactions between gut commensals, condition. Therefore, microbial alteration can be beneficial during neurological and immunological responses. This was also observed autoimmune disorders. However, several lines of evidence suggest in case of type I diabetes mellitus.3 Authors showed the role of the role of gender-bias, (regulation of sex-hormones by microbio- early-life microbiota influence on puberty and sex-hormonal levels ta) in numerous diseases. This editorial aims to throw light on the in a non-obese diabetic model. When mice were made germ-free, novel, emerging triangular relationship between host microbiota, the circulatory testosterone levels were higher in female mice than sex hormones (testosterone, progesterone and estrogen) and im- in male mice. In contrast, protection from type I diabetes melli- mune responses cumulatively termed as “Microgenderome”. tus was lost in germ-free mice, where testosterone levels were also found to be low to untraceable. This study provides the evidence of bi-directional relation between sex-hormones and microbiota Microgenderome is an interaction between microbio- during autoimmune diseases.

CONFLICTS OF INTEREST tween microbiota and sex-hormones is referred to as “interking- dom signaling”. This type of signaling is commonly used by mi- The authors declare that they have no conflicts of interest. crobes during bacterial or viral infections to modulate the outcome of the infection.4 Numerous studies have reported that males are

References

1. YurkovetskiyLAPickardJMChervonskyAV. Microbiota and tion of immune response by sex-hormones compared to females, autoimmunity: exploring new avenues. Cell Host Microbe. 2015; 17: indicating the role of sex-hormones in host-microbial interactions. 548-552. doi: 10.1016/j.chom.2015.04.010 However, the exact mechanism on how sex-hormones modulate immune responses in microbial interactions is still unclear. To10.1016/j.chom.2015.04.010 https://doi.org/10.1016/j.chom.2015.04.010
2. WallisAButtHBallMLewisDPBruckD. Support for the investigate this issue, Fransen and group used an animal model microgenderome: Associations in a human clinical population. Sci where the gut microbiota from conventional males or females was Rep. 2016; 6: 19171. doi: 10.1038/srep19171 transferred to germ-free mice of same or opposing gender.5 Interestingly, the type I interferon (pro-inflammatory cytokine) levels10.1038/srep19171 https://doi.org/10.1038/srep19171
3. MarkleJGFrankDNMortin-TothS. Sex differences were already elevated in intestine of germ-free females. Presence in the gut microbiome drive hormone-dependent regulation of of certain bacteria in male microbiota induced weight loss and inautoimmunity. Science. 2013; 339: 1084-1088. doi: 10.1126/sciflammation in female mice after transfer. The study revealed presence.1233521 ence of sex-specific microbial composition and their expansion in absence of innate immune responses thereby demonstrating the10.1126/sciflammation https://doi.org/10.1126/sciflammation
4. García-GómezEGonzález-PedrajoBCamacho-ArroyoI. Role link between gut microbes, gender and immunity. Taken together, of sex steroid hormones in bacterial-host interactions. Biomed Res authors suggested gender should be considered as an important Int. 2013; 2013: 928290. doi: 10.1155/2013/928290 variable in developing therapeutic strategies to target gut microbiota in various disorders10.1155/2013/928290 https://doi.org/10.1155/2013/928290
5. FransenFvan BeekAABorghuisT. The impact of gut microbiota on gender-specific differences in immunity. Front Im- A close association of sex-hormones, gut microbiota and munol. 2017; 8: 754. doi: 10.3389/fimmu.2017.00754 immune response was observed in experimental models studying trabecular bone loss. Under germ-free condition, sex-hormone10.3389/fimmu.2017.00754 https://doi.org/10.3389/fimmu.2017.00754
6. LiJYChassaingBTyagiAM. Sex steroid deficiency-assocideficiency increase gut permeability and upregulated inflammaated bone loss is microbiota dependent and prevented by probiottory cytokines. Estrogen deficiency-associated bone loss is microics. J Clin Invest. 2016; 126: 2049-2063. doi: 10.1172/JCI86062 biota dependent and is prevented by probiotics. Consistent with this study, it was also observed that certain lactobacilli probiotic10.1172/jci86062 https://doi.org/10.1172/jci86062
7. BrittonRAIrwinRQuachD. Probiotic L. reuteri treatmodulated gut microbiota, downregulated inflammation and pre- 7 ment prevents bone loss in a menopausal ovariectomized mouse vented trabecular bone loss in ovariectomized mice. From these model. J Cell Physiol. 2014; 229: 1822-1830. doi: 10.1002/jcp.24636 studies, it is understood that depletion of sex-hormones increases the gut permeability and alters the microbial composition leading10.1002/jcp.24636 https://doi.org/10.1002/jcp.24636
8. FlakMBNevesJFBlumbergRS. Welcome to the microgento increase in osteoclastogenic inflammation. Supplementing with derome. Science. 2013; 339(6123): 1044-1045. doi: 10.1126/scicertain probiotic bacteria ameliorated bone loss by repopulating ence.1236226 microbiota and down streaming the associated inflammatory cyto- 8,9 kines.8,910.1126/scicertain https://doi.org/10.1126/scicertain
9. BronPAvan BaarlenPKleerebezemM. Emerging molecular insights into the interaction between probiotics and the host in-Taken together, these observations suggest a pivotal role 8 testinal mucosa. Nat Rev Microbiol. 2012; 10: 66-78. doi: 10.1038/ of microgenderome in human health. Human clinical research nrmicro2690 should consider sex comparison as an important variable. Future studies should consider measuring sex hormone levels to extend the current knowledge on triangular relation between microbes, sex hormones and related immune responses