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Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection.
Spagnolello, O, Pinacchio, C, Santinelli, L, Vassalini, P, Innocenti, GP, De Girolamo, G, Fabris, S, Giovanetti, M, Angeletti, S, Russo, A, et al
Chemotherapy. 2021;(1-2):24-32
Abstract
Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.
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Joint Effect of Maternal Tobacco Smoking and Pregestational Diabetes on Preterm Births and Congenital Anomalies: A Population-Based Study in Northern Italy.
Borsari, L, Malagoli, C, Werler, MM, Rothman, KJ, Malavolti, M, Rodolfi, R, De Girolamo, G, Nicolini, F, Vinceti, M
Journal of diabetes research. 2018;:2782741
Abstract
Smoking and pregestational diabetes (PGD) are recognized risk factors for adverse pregnancy outcomes, but to date, no population-based study has investigated their joint effects. Using hospital discharges, we identified all women with PGD delivering in Emilia-Romagna region during 2007-2010 matched 1 : 5 with parturients without diabetes. Our study endpoints were preterm births and congenital anomalies. We measured interaction between PGD and maternal smoking, by calculating excess prevalence and prevalence ratio due to interaction, relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (S). Analyses were performed in the overall study population and in the subgroup whose PGD was validated through diabetes registers. The study included 992 women with PGD (10.5% smokers) and 4788 comparison women (11.9% smokers). The effects of PGD and maternal tobacco smoking were greater than additive for both preterm birth (excess prevalence due to interaction = 11.7%, excess ratio due to interaction = 1.5, RERI = 2.39, AP = 0.51, S = 2.82) and congenital anomalies (excess prevalence due to interaction = 2.2%, excess ratio due to interaction = 1.3, RERI = 1.33, AP = 0.49, S = 5.03). Joint effect on both endpoints was confirmed in the subgroup whose PGD status was validated. In conclusion, we found that maternal tobacco smoking and PGD intensify each other's effect on preterm birth and congenital anomalies.
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Impact of switching from lopinavir/ritonavir to boosted and un-boosted atazanavir on glucose metabolism: the ATAzanavir & GLUcose metabolism (ATAGLU) study.
d'Ettorre, G, Ceccarelli, G, Zaccarelli, M, Ascoli-Bartoli, T, Bianchi, L, Bellelli, V, De Girolamo, G, Serafino, S, Giustini, N, Mastroianni, CM, et al
International journal of STD & AIDS. 2016;(8):638-43
Abstract
Previous studies have reported that protease inhibitors (PIs) can contribute to glycaemic alterations. However, there are few trials examining the direct effect of a single PI. The objective of the study was to evaluate the modifications of glucose and lipid profiles after a switch from lopinavir/ritonavir (LPV/r) to atazanavir, used as ritonavir-boosted (ATV/r) or un-boosted. We conducted a retrospective observational cohort study on the effect of ATV/(r) on glycaemic metabolism (ATAGLU) in patients with undetectable levels of HIV-RNA who switched from LPV/r. In total, 235 patients treated for 48 weeks with LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) and with undetectable HIV-RNA were included: 134 continued LPV/r after the initial 48 weeks and 101 switched to ATV(/r) (18.3% to ATV; 24.7% to ATV/r). A significant decrease in mean glucose level and insulin resistance was observed in patients who switched to ATV(/r). The mean cholesterol triglyceride levels increased in the LPV/r group and decreased among the patients who switched. A significant increase of CD4 T cells with undetectable levels of HIV-RNA was observed in all groups. The long-term results obtained in this real-life study suggest that patients who have achieved initial suppression on a regimen including LPV/r + two NRTIs can switch to ATV/(r) + two NRTIs with an improvement in lipid and glycaemic metabolism.
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Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the "Probio-HIV" Clinical Trial.
d'Ettorre, G, Ceccarelli, G, Giustini, N, Serafino, S, Calantone, N, De Girolamo, G, Bianchi, L, Bellelli, V, Ascoli-Bartoli, T, Marcellini, S, et al
PloS one. 2015;(9):e0137200
Abstract
BACKGROUND HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation. METHODS In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma. RESULTS We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls. CONCLUSIONS Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis. TRIAL REGISTRATION ClinicalTrials.gov NCT02164344.