1.
Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy.
Siena, M, Laterza, L, Matteo, MV, Mignini, I, Schepis, T, Rizzatti, G, Ianiro, G, Rinninella, E, Cintoni, M, Gasbarrini, A
Microorganisms. 2021;9(3)
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During pregnancy, several adaptations occur in the female organism. In fact, from fertilization until delivery, the maternal body changes and activates a series of physiological transformations to welcome the new life. The microbiota as a component of human bodies is subject to these modifications. This study is a review that focused on gut and reproductive tract microbiota variations during physiologic pregnancy and in case of pregnancy complications, particularly gestational diabetes mellitus (GDM), pre-eclampsia (PE), and preterm birth (PTB). Results show that: - during pregnancy, major changes have been seen in mothers’ gut microbiota. Between the first and third trimester of pregnancy, to support the foetus growth, there is a shift towards communities of microbes implicated in energy production and storage. - in nonpregnant women, vaginal microbiota could be classified into five major types, representing the community state types. - meconium’s microbes seems to be dominated by the Enterobacteriaceae family, suggesting prenatally stepwise colonization. - gut microbiota may contribute to enhanced insulin resistance in early pregnancy (1st and 2nd trimester). - microbiota imbalances in PE women are related not only with blood pressure levels but also with markers of kidney dysfunction. Thus, it is of key importance to understand the role of microbiota and other factors involved in the etiopathogenesis of PE - dysbiosis is related to PTB (however, further studies are necessary to better understand the correlation between this pregnancy complication and the specific microbiota alteration). Authors conclude that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
Abstract
Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
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Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.
Leong, KSW, Jayasinghe, TN, Wilson, BC, Derraik, JGB, Albert, BB, Chiavaroli, V, Svirskis, DM, Beck, KL, Conlon, CA, Jiang, Y, et al
JAMA network open. 2020;3(12):e2030415
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Obesity has become a global pandemic even in adolescents. Lifestyle interventions have had limited impact on this cohort and drugs targeting obesity are often unlicensed in children. The gut microbiome has a role in weight regulation and may be a new target in adolescents with obesity. This randomised control trial of 87 adolescents with obesity over 26 weeks, aimed to assess if faecal microbiome transfer (FMT), which is a method whereby faecal matter is transplanted from one person to another, can be used to treat obesity. The results showed that FMT did not have an effect on body mass index (BMI) and the intervention group had a marginally increased BMI after FMT. Other disorders associated with obesity such as blood sugar levels were also unaffected by FMT, however there was a reduction in fat storage around the middle. It was concluded that FMT alone is not adequate to improve obesity in adolescents, but may reduce fat stored around the middle. Healthcare professionals could use this study to understand that simply transplanting one person’s gut microbiome to another, may not be enough. Targeted personalised approaches may be required, however further research is needed.
Abstract
Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.
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Non-Nutritive Sweeteners and Their Implications on the Development of Metabolic Syndrome.
Liauchonak, I, Qorri, B, Dawoud, F, Riat, Y, Szewczuk, MR
Nutrients. 2019;11(3)
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Artificial sweeteners, such as aspartame, neotame, saccharin, sucralose, and stevia are widely promoted as low-calorie alternatives to sugar and are known as non-nutritive sweeteners (NNS). Generally, they have been considered as a healthy option to replace sugars, but data is emerging that they may influence obesity and metabolic syndrome (METs) and contribute to the development of type II diabetes. These non-nutritive sweeteners can be thousands of times sweeter than sugar and have been widely adopted by the food industry to help reduce calories, and promote weight loss and diabetic products. It is believed that 25% of children and 41% of adults consume low-calorie sweeteners regularly, with the beverage industry relying heavily on them. However, it is now been shown that these sweeteners can cause imbalances to gut bacteria and interact with taste receptors and insulin signalling. These findings mean that artificial sweeteners may trigger the same hormonal response as sugar by releasing insulin and overtime lead to insulin resistance, obesity, and overall metabolic syndrome. Finally, there is evidence that our body develops a learned response to sweeteners which paradoxically leads to weight gain.
Abstract
Individuals widely use non-nutritive sweeteners (NNS) in attempts to lower their overall daily caloric intake, lose weight, and sustain a healthy diet. There are insufficient scientific data that support the safety of consuming NNS. However, recent studies have suggested that NNS consumption can induce gut microbiota dysbiosis and promote glucose intolerance in healthy individuals that may result in the development of type 2 diabetes mellitus (T2DM). This sequence of events may result in changes in the gut microbiota composition through microRNA (miRNA)-mediated changes. The mechanism(s) by which miRNAs alter gene expression of different bacterial species provides a link between the consumption of NNS and the development of metabolic changes. Another potential mechanism that connects NNS to metabolic changes is the molecular crosstalk between the insulin receptor (IR) and G protein-coupled receptors (GPCRs). Here, we aim to highlight the role of NNS in obesity and discuss IR-GPCR crosstalk and miRNA-mediated changes, in the manipulation of the gut microbiota composition and T2DM pathogenesis.