Periodic Reporting for period 1 - SEMICYCLE (Deciphering female’s SEx hormones - MIcrobiota interactions during a menstrual CYCLE for an efficient personalized medicine in cardiometabolic disorders)
Okres sprawozdawczy: 2023-05-01 do 2025-10-31
Cardiometabolic disorders (CMD), a group of conditions that include cardiovascular diseases, type 2 diabetes and metabolic syndrome, are characterized by dysfunction of glycemic and/or lipid metabolism. Clinical manifestations, severity and progression are different between sexes, the underlying mechanisms of which are largely unknown. The poorer prognosis in women globally calls for an urgent need for better women’s tailored prevention and treatment strategies. Still, for an efficient personalized strategy, female-specific mechanisms must be identified. The SEMICYCLE project will systematically investigate female’s sex hormones microbiota interactions to unravel female-specific microbiota features regulating glycemic and lipid metabolism in women during homeostasis and diseases. We will study the interaction among host genome, gut microbiome, fecal metabolome, and vaginal microbiome in the regulation of females’ glycemic and/or lipid metabolism by following up longitudinally a cohort of up to 300 women (Women4Health), as well as interrogating already existing cohorts totaling more than 4,000 women. We expect this project will reveal previously unknown microbiota regulators of CMD in women thus offering alternative routes for prevention, diagnosis and treatments for CMD in women, a necessary step for an efficient personalized medicine.
In the past 24 months, we set up the Women4Health cohort (www.women4health.it) central to the SEMICYCLE project. Finding potential volunteers who met the required enrolment criteria and were willing to dedicate to the study observation period, was a challenging task. We initially set up the first recruitment center in Trieste (IRCCS Burlo Garofolo, Italy), and recently two additional centers have joined: the University Medical center in Cagliari (AOU Cagliari, Italy), and the University Medical Center in Bologna (IRCCS Policlinico San'Orsola, Bologna, Italy). Recruitment is still ongoing.
While the data is collected, we start processing data and biological samples as they came in. This allowed us to set up all protocols for the lab and to develop the bioinformatic and statistical workflow. In particular, the development of the bioinformatic and statistical analyses for handling longitudinal data and for the identification of causal relationship is an important achievement since no other pipelines were available in our group and this is yet uncommon on the scientific field.
Using the preliminary data collected, we characterized both the gut and vaginal microbiomes, as well as proteomic data, along with sex hormones, cardiometabolic blood biomarkers and questionnaire-derived data and evaluated longitudinal changes and causal relationships. We identified several variables for all data type (microbiome, blood traits, proteomics) that significantly change during the menstrual cycles, along the sex-hormones. We also identified several interesting causal relationships. We expect the recruitment of volunteers to be completed by next year and we will extend the analyses to the largest set of data to confirm their robustness. Join effort with our collaborators will then be pivotal to evaluate replication of the findings in other cohorts, and to exploit their impact on cardiometabolic diseases.
While the data is collected, we start processing data and biological samples as they came in. This allowed us to set up all protocols for the lab and to develop the bioinformatic and statistical workflow. In particular, the development of the bioinformatic and statistical analyses for handling longitudinal data and for the identification of causal relationship is an important achievement since no other pipelines were available in our group and this is yet uncommon on the scientific field.
Using the preliminary data collected, we characterized both the gut and vaginal microbiomes, as well as proteomic data, along with sex hormones, cardiometabolic blood biomarkers and questionnaire-derived data and evaluated longitudinal changes and causal relationships. We identified several variables for all data type (microbiome, blood traits, proteomics) that significantly change during the menstrual cycles, along the sex-hormones. We also identified several interesting causal relationships. We expect the recruitment of volunteers to be completed by next year and we will extend the analyses to the largest set of data to confirm their robustness. Join effort with our collaborators will then be pivotal to evaluate replication of the findings in other cohorts, and to exploit their impact on cardiometabolic diseases.
Current results from our study are already significant in the field of vaginal microbiome research. We observed that a particular Lactobacillus species is highly predominant in Italian women, in contrast to previous studies conducted in Northern European countries. This insight is crucial for designing targeted interventions to restore a healthy vaginal microbiome while taking into account population-specific assets.
Future findings from this study are expected to uncover previously unknown microbiota regulators of cardiometabolic disorders (CMD) in women. These discoveries will provide key elements for the development of novel microbiota-based compounds or functional approaches, which could serve as alternative routes for the prevention, diagnosis, and treatment of CMD in women.
To ensure further uptake and success, additional research and clinical validation will be required, as well as demonstration activities and support for early translational steps.
Future findings from this study are expected to uncover previously unknown microbiota regulators of cardiometabolic disorders (CMD) in women. These discoveries will provide key elements for the development of novel microbiota-based compounds or functional approaches, which could serve as alternative routes for the prevention, diagnosis, and treatment of CMD in women.
To ensure further uptake and success, additional research and clinical validation will be required, as well as demonstration activities and support for early translational steps.