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Lack of association between endocrine disrupting chemicals and male fertility: A systematic review and meta-analysis.
Martínez, MÁ, Marquès, M, Salas-Huetos, A, Babio, N, Domingo, JL, Salas-Salvadó, J
Environmental research. 2023;217:114942
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Exposure to natural or synthetic chemicals is directly related to environmental conditions, dietary and other lifestyle factors. Some of these chemicals are named endocrine disrupting chemicals (EDCs) because of their capability to interfere with the endocrine system. The aim of this study was to summarise and explore the association between exposure to EDCs and human male fertility indicators. This study is a systematic review and meta-analysis of seven studies; 4 assessed bisphenol A (BPA) in urine and sperm quality parameters, while 3 articles evaluated PCB153 [polychlorinated biphenyls] in serum and sperm quality parameters. Results show that there weren’t any positive or inverse associations between BPA or PCB153 and the sperm parameters analysed. Authors conclude that the systematic review showed a high disparity between studies, making difficult a consensus on the possible detrimental effect of the 12 groups of EDCs on male fertility. Thus, no conclusive statements can be drawn. Further studies are needed in order to provide more robust data.
Abstract
The incidence of infertility currently affects about 15% of the world's population. Male factors are estimated to be responsible for up to 40-50% of these cases. While the cause of these reproductive disorders is still unclear, the exposure to a family of ubiquitous compounds in our daily life, named endocrine disrupting chemicals (EDCs) could be involved. This paper was aimed at performing a systematic review and meta-analysis of population studies exploring whether human male exposure to EDCs affects male fertility. Clinical and observational studies assessing the exposure to EDCs along with sperm quality, the most common reproductive disorders, sperm DNA damage, sperm oxidative stress, fertilization rate, implantation rate, clinical pregnancy rate, live birth rate, and miscarriage rate were included. The quality assessment tool from the NHLBI-NIH was used to assure that studies met standardized quality criteria. Sensitivity analysis and heterogeneity among studies was assessed. Overall, the 32 selected articles, including 7825 individuals in the systematic review, explored 12 families of EDCs. The results revealed a high heterogeneity among studies in relation to the association between exposure to EDCs and the endpoints analyzed. Meta-analyses were performed with data from 7 articles including 479 individuals, 4 articles assessing the association between BPA in urine and sperm quality, and 3 articles evaluating PCB153 in serum and sperm quality. In the meta-analysis, we identified an unpredicted significant positive association between PCB153 exposure and sperm concentration. However, it would not be clinically relevant. No positive or inverse associations were found neither for BPA, nor for PCB153 and the rest of sperm parameters analyzed. The high disparity between studies made difficult to draw conclusions on the potential harmful effects of EDCs on male fertility. Consequently, to delineate the potential relationship that EDCs can have on male fertility, an important condition stressing the health system, further investigations are required.
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Mycotoxin-Linked Mutations and Cancer Risk: A Global Health Issue.
Ekwomadu, T, Mwanza, M, Musekiwa, A
International journal of environmental research and public health. 2022;19(13)
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Mycotoxins are toxic substances produced by fungi, which can be found in common foods like maize, wheat, nuts, and foods containing them. Mycotoxins such as aflatoxins, ochratoxin, fumonisins, zearalenone, and some Penicillium toxins can alter genetic material. According to previous studies, they can damage genetic material and affect cell growth. Usage of chemicals such as fertilizers and fungicides is a common practice in the agricultural industry to protect plants from fungus and to feed them. However, fungicides can accelerate mycotoxin production. 16 studies were included in this Systematic Review and 11 in Meta-Analysis. This research looked at the harmful effects of mycotoxins such as aflatoxins, fumonisins, ochratoxin, T2, zearalenone, and some Penicillium toxins in causing cancers. The researchers evaluated the link between aflatoxin exposure and liver cancer, fumonisin B1 exposure and liver cancer, zearalenone exposure and breast cancer, zearalenone exposure and cervical cancer, citrinine and patulin exposure and colorectal cancer, and NEO, HT-2, and T-2 exposure and Oesophageal cancer. This research did not show significant associations between various mycotoxins and cancer risk. As currently, most studies are primarily focused on aflatoxin; more robust studies are needed to assess the cancer risk associated with different mycotoxin exposure. Using the results of this study, healthcare professionals can gain a better understanding of how mycotoxins affect our bodies.
Abstract
Humans continue to be constantly exposed to mycotoxins, mainly through oral exposure (dietary), inhalation, or dermal contact. Recently, it has been of increasing interest to investigate mycotoxin-linked carcinogenicity. This systematic review was conducted to synthesize evidence of the association between mycotoxin-linked mutations and the risk of cancer, to provide an overview of the data linking exposure to different mycotoxins with human cancer risk, and to provide an update on current research on the risk of cancer associated with human exposure to mycotoxins. PRISMA guidelines were used when conducting the systematic review. PubMed, MEDLINE, and CINAHL electronic databases were comprehensively searched to extract the relevant studies published from inception to May 2022. A total of sixteen relevant studies (4907 participants) were identified and included in this review. Of these, twelve studies were from Asia, while four of the studies were conducted in Africa. The overall meta-analysis result found no significant association, although some of the studies confirmed an association between mycotoxin-linked mutations and primary liver cancer risk. Mainly, the experimental studies have shown associations between mycotoxin-linked mutations and cancer risk, and there is a need for researchers to confirm these links in epidemiological studies in order to guide public health policies and interventions.
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The role of gut microbiome in inflammatory skin disorders: A systematic review.
Widhiati, S, Purnomosari, D, Wibawa, T, Soebono, H
Dermatology reports. 2022;14(1):9188
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Gut-skin axis refers to the complex cross-talk between gut bacteria and skin. Although the exact mechanism underlying chronic inflammatory skin conditions is unknown, imbalances in the composition of gut microbes are believed to play a role. Twenty-three studies were included in this systematic review to assess whether gut microbial imbalance may contribute to inflammatory skin conditions such as Psoriasis, Acne Vulgaris, Atopic Dermatitis, and Urticaria. According to this systematic review, immune stimulation, inflammation, and disruption of bacterial composition are common mechanisms in all these skin disorders. A western diet and environmental exposures are found to be contributing to the disruption of bacteria and the pathology of these skin disorders. It has been observed that friendly gut bacteria such as Bifidobacterium are reduced in people with inflammatory skin conditions, whereas elevated levels of pathogenic bacteria such as E. coli and Proteobacteria are present in the gut of patients with inflammatory skin conditions. The abundance of anti-inflammatory bacteria such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Clostridium leptum, Lactobacillus, and Bifidobacterium may protect against inflammatory skin conditions. Further robust studies are required to evaluate the pathogenesis behind inflammatory skin conditions as well as the involvement of gut bacteria in the development and progression of the disease. Healthcare professionals can gain a deeper understanding of gut bacteria that contribute to the pathology of inflammatory diseases as well as how clinically using anti-inflammatory bacterial species may improve the condition of individuals suffering from inflammatory skin conditions.
Abstract
The close relationship between the intestine and the skin has been widely stated, seen from gastrointestinal (GI) disorders often accompanied by skin manifestations. Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders are still unclear. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis. This systematic review aimed to explore the associations between the gut microbiome with inflammatory skin disorders, such as acne, psoriasis, atopic dermatitis, and urticaria, and to discover the advanced concept of this relationship. The literature search was limited to any articles published up to December 2020 using PubMed and EBSCOHost. The review followed the PRISMA guidelines for conducting a systematic review. Of the 319 articles screened based on title and abstract, 111 articles underwent full-text screening. Of these, 23 articles met our inclusion criteria, comprising 13 atopic dermatitis (AD), three psoriasis, four acne vulgaris, and four chronic urticaria articles. Acne vulgaris, atopic dermatitis, psoriasis, and chronic urticaria are inflammation skin disorders that were studied recently to ascertain the relationship of these disorders with dysbiosis of the GI microbiome. All acne vulgaris, psoriasis, and chronic urticaria studies stated the association of gut microbiome with skin manifestations. However, the results in atopic dermatitis are still conflicting. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorders.
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Effects of Hemp Sanitary Pads on the Vaginal Microecology.
Sun, Y, Li, C, Yan, Y, Lai, A, Peng, X, Yue, X, Li, Y, Liu, J, Liu, Y
Computational and mathematical methods in medicine. 2022;2022:4435722
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Under ideal situations, women have a variety of microbes that reside in the vagina which form the normal vaginal microbiome. When combined, the vaginal microbial flora, endocrine regulation system, anatomic structure of the vagina, and local endocrine system constitute the vaginal microecosystem, which is in turn part of the entire human microecosystem. In fact, the choice of appropriate sanitary pads is of high importance during the menstrual period. The aim of this study was to evaluate the effect of hemp cotton sanitary pads on the vaginal microecology. The study is a randomised controlled field trial study which recruited women of childbearing age. The patients were randomly divided into two groups (experimental and control groups). The control group was further divided into 2 subgroups. The subjects in the experimental group used hemp sanitary pads. Results show that: - among women with a normal vaginal microecosystem or a vaginal microecologic imbalance at baseline, the vaginal cleanliness grade and overall vaginal microecologic status were better if hemp sanitary pads were used rather than the ordinary cotton sanitary pads. - there was no significant difference in the vaginal pH values between the two groups. - hemp sanitary pads had no therapeutic effect against vaginal infections. Authors conclude that the use of hemp cotton sanitary pads during menstruation, by women without vaginal inflammation, can help maintain balanced vaginal microecology which will help to prevent reproductive tract infections.
Abstract
OBJECTIVE To evaluate the effect of hemp cotton sanitary pads on the vaginal microecology. METHODS A randomized controlled field trial was used to recruit 1002 community-based women of childbearing age. The women were randomly divided into experimental and control groups. The experimental group used hemp cotton sanitary pads, while the control group used two types of cotton sanitary randomly chosen from the top five sanitary pads in terms of market share in China. The vaginal microecology was compared between the two groups after three months. RESULTS According to the vaginal microecologic examination results at baseline, 1002 women were included in 3 groups: normal vaginal microecologic, vaginal microecological disorders, and suspected vaginal infections. The number of patients in three groups were 39 (3.9%), 652 (65.1%), and 311 (31%), respectively. Three months later, the vaginal microecologic status and vaginal pH value of the suspected vaginal infection group were not significantly different between the experimental group and control group. The experimental group outperformed the control group with respect to vaginal cleanliness and vaginal microecology status in the women without a vaginal infection (normal vaginal microecology or microecological disorders group). The rate of abnormal cleanliness in the experimental group was lower than the control group (31.95% [108/338] vs. 43.62% [154/353]). The incidence of suspected vaginitis in the experimental group was lower than the control group (15.29% [51/338] vs. 23.51% [83/353]). CONCLUSION For women without vaginal inflammation, the use of hemp cotton sanitary pads during menstruation can help maintain the balance of the vaginal microecology to prevent reproductive tract infections.
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A Deep Look at the Vaginal Environment During Pregnancy and Puerperium.
Severgnini, M, Morselli, S, Camboni, T, Ceccarani, C, Laghi, L, Zagonari, S, Patuelli, G, Pedna, MF, Sambri, V, Foschi, C, et al
Frontiers in cellular and infection microbiology. 2022;12:838405
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In healthy reproductive-aged women, the vaginal microbiome is generally dominated by members of the Lactobacillus genus. Lactobacilli promote the maintenance of the vaginal health, preventing the colonization and growth of adverse microorganisms through various mechanisms. The composition of the vaginal bacterial communities and related metabolites play a crucial role in maternal-foetal health. The aim of this study was to deepen the characteristics of the vaginal environment in a cohort of Caucasian women with a normal pregnancy throughout their different gestational ages (i.e., first, second, third trimester) and puerperium. This study is a prospective study of sixty-three Caucasian pregnant women. Participants were enrolled and sampled during all gestational ages; for 30 of them, clinical and microbiological data were also available for the puerperium. Additionally, 9 women who had a spontaneous miscarriage at the first trimester of pregnancy (gestational age: 11-13 weeks) during the study were included. Results show that: - irrespective of the period and type of pregnancy, bacterial vaginosis cases were characterised by a dramatic reduction of Lactobacillus and an increase of anaerobic bacteria. - the vaginal microbiome becomes more stable throughout the entire pregnancy, being less diverse and mainly dominated by lactobacilli. - women receiving an intrapartum antibiotic prophylaxis for Group B Streptococcus were characterized by a vaginal abundance of Prevotella compared to untreated women. - at the puerperium, a significantly lower content of Lactobacillus and higher levels of Gardnerella, Prevotella, Atopobium, and Streptococcus were observed. Authors conclude that their findings may help implement ‘prognostic’ criteria (e.g., evaluation of the risk of spontaneous miscarriage based on the microbiome/metabolome profiles), as well as strategies for the prevention of early pregnancy loss, based on the ‘manipulation’ of the vaginal bacterial inhabitants.
Abstract
A deep comprehension of the vaginal ecosystem may hold promise for unraveling the pathophysiology of pregnancy and may provide novel biomarkers to identify subjects at risk of maternal-fetal complications. In this prospective study, we assessed the characteristics of the vaginal environment in a cohort of pregnant women throughout their different gestational ages and puerperium. Both the vaginal bacterial composition and the vaginal metabolic profiles were analyzed. A total of 63 Caucasian women with a successful pregnancy and 9 subjects who had a first trimester miscarriage were enrolled. For the study, obstetric examinations were scheduled along the three trimester phases (9-13, 20-24, 32-34 gestation weeks) and puerperium (40-55 days after delivery). Two vaginal swabs were collected at each time point, to assess the vaginal microbiome profiling (by Nugent score and 16S rRNA gene sequencing) and the vaginal metabolic composition (1H-NMR spectroscopy). During pregnancy, the vaginal microbiome underwent marked changes, with a significant decrease in overall diversity, and increased stability. Over time, we found a significant increase of Lactobacillus and a decrease of several genera related to bacterial vaginosis (BV), such as Prevotella, Atopobium and Sneathia. It is worth noting that the levels of Bifidobacterium spp. tended to decrease at the end of pregnancy. At the puerperium, a significantly lower content of Lactobacillus and higher levels of Gardnerella, Prevotella, Atopobium, and Streptococcus were observed. Women receiving an intrapartum antibiotic prophylaxis for Group B Streptococcus (GBS) were characterized by a vaginal abundance of Prevotella compared to untreated women. Analysis of bacterial relative abundances highlighted an increased abundance of Fusobacterium in women suffering a first trimester abortion, at all taxonomic levels. Lactobacillus abundance was strongly correlated with higher levels of lactate, sarcosine, and many amino acids (i.e., isoleucine, leucine, phenylalanine, valine, threonine, tryptophan). Conversely, BV-associated genera, such as Gardnerella, Atopobium, and Sneathia, were related to amines (e.g., putrescine, methylamine), formate, acetate, alcohols, and short-chain fatty-acids (i.e., butyrate, propionate).
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Prenatal exposure to phthalate and decreased body mass index of children: a systematic review and meta-analysis.
Lee, DW, Lim, HM, Lee, JY, Min, KB, Shin, CH, Lee, YA, Hong, YC
Scientific reports. 2022;12(1):8961
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Phthalates are widely used chemicals to improve the utility of plastics and personal care products. Phthalates can be classified as high-molecular-weight phthalates and low-molecular-weight phthalates. The aim of this study was to clarify whether prenatal and postnatal exposures to phthalates are associated with physical growth as measured by body composition indices in children. This study is a systematic literature review and meta-analysis of 39 studies about the association of phthalates with body composition indices among children. Results showed that prenatal exposure to phthalates is significantly associated with low body mass index in children, but not with body fat mass. In addition, prenatal phthalate exposure may affect the disturbance of normal growth of children rather than act as an obesogen. Authors conclude that it is necessary to administer stricter and broader regulations on phthalates in living environments.
Abstract
Phthalates are well-known endocrine-disrupting chemicals. Many detrimental health effects of phthalates were investigated, but studies on the association of phthalates with obesity in children showed inconsistent results. Thus, this systematic review and meta-analysis were performed to clarify whether prenatal and postnatal exposures to phthalates are associated with physical growth disturbances in children. We performed the systematic review and meta-analysis following the PRISMA 2020 statement guidelines, and found 39 studies that met our inclusion criteria, including 22 longitudinal and 17 cross-sectional studies. We observed a significant negative association between the prenatal exposure to DEHP and the body mass index (BMI) z-score of the offspring (β = - 0.05; 95% CI: - 0.10, - 0.001) in the meta-analysis, while no significant association between the prenatal exposure to DEHP and the body fat percentage of the offspring was observed (β = 0.01; 95% CI: - 0.41, 0.44). In the systematic review, studies on the association between phthalates exposure in childhood and obesity were inconsistent. Prenatal exposure to phthalates was found to be associated with decreased BMI z-score in children, but not associated with body fat percentage. Our findings suggest that phthalates disturb the normal muscle growth of children, rather than induce obesity, as previous studies have hypothesized.
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Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.
Aghapour, M, Tulen, CBM, Abdi Sarabi, M, Weinert, S, Müsken, M, Relja, B, van Schooten, FJ, Jeron, A, Braun-Dullaeus, R, Remels, AH, et al
Cells. 2022;11(11)
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Cigarette smoking can affect airway epithelial cells, causing overproduction of mucus, damage, and inflammation, which may result in the progression of airway diseases. Airway epithelial cells (AEC) rely on mitochondria for energy, and mitochondrial dysfunction may affect innate immunity and the integrity of the airway epithelium. Cigarette smoking is found to accelerate mitochondrial damage within AEC. Maintaining a normal microbial composition within the respiratory tract is essential for maintaining immunity. There is evidence that smoking cigarettes disrupts the microbial composition and increases the spread of pathogenic bacteria such as Streptococcus pneumoniae (Sp) which causes inflammation. By exposing 16HBE cells to Sp and cigarette smoke extract (CSE), this study investigated the effect of cigarette smoking on mitochondrial dysfunction in ACE in an in vitro model. Additionally, the study examined the direct and indirect pathways involved in cigarette smoking-induced mitochondrial dysfunction and altered innate immune response to Sp infection. CSE exposure decreases mitochondrial complex protein levels and mitochondrial membrane potential, which affects energy production. It also increases mitochondrial oxidative stress and mitochondrial degradation. All these factors lead to mitochondrial dysfunction in ACE. CSE exposure to ACE was associated with altered gene expression in the tight and adherence junctions that serve as a protective barrier against pathogens and pollutants and reduced type I interferon immune responses to Sp. Using the results of this study, healthcare professionals can gain a better understanding of the impact of cigarette smoking on mitochondrial dysfunction and how it increases susceptibility to Sp-related immune responses. It is necessary to conduct further studies to evaluate the effects of cigarette smoking on mitochondrial dysfunction, microbial composition disruption, and the interaction between AECs and elevated immune responses.
Abstract
Mitochondrial functionality is crucial for the execution of physiologic functions of metabolically active cells in the respiratory tract including airway epithelial cells (AECs). Cigarette smoke is known to impair mitochondrial function in AECs. However, the potential contribution of mitochondrial dysfunction in AECs to airway infection and airway epithelial barrier dysfunction is unknown. In this study, we used an in vitro model based on AECs exposed to cigarette smoke extract (CSE) followed by an infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress as an indicator of mitochondrial stress were quantified upon CSE and Sp treatment. In addition, expression of proteins associated with mitophagy, mitochondrial content, and biogenesis as well as mitochondrial fission and fusion was quantified. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with indices of mitochondrial function. We observed that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp.
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Effects of early-life antibiotics on the developing infant gut microbiome and resistome: a randomized trial.
Reyman, M, van Houten, MA, Watson, RL, Chu, MLJN, Arp, K, de Waal, WJ, Schiering, I, Plötz, FB, Willems, RJL, van Schaik, W, et al
Nature communications. 2022;13(1):893
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Disturbances of the gut microbial community composition after birth are associated with a broad spectrum of health problems in early infancy and later in life. The ecological side effects of antibiotics may be even more pronounced and persistent when administered in the early assembly phase of the neonatal gut microbiome in the first weeks of life. The aim of this study was to identify the antibiotic regimen with the least ecological and antimicrobial resistance (AMR) gene selection effects. This study was a randomised controlled study in 147 infants who required broad-spectrum antibiotics for treatment of (suspected) early-onset neonatal sepsis (sEONS) in their first week of life. Infants were randomly allocated 1:1:1 to three most commonly prescribed intravenous antibiotic combinations. Results showed that antibiotic-treated infants show temporarily reduced gut microbial diversity, and major and prolonged ecological perturbations, compared with healthy term-born controls. Furthermore, there was also a shift in AMR gene profile. Authors conclude that there are significant long-term effects of broad-spectrum antibiotic treatment. In fact, their findings suggest that more emphasis should be put on reducing the number of neonates that receive broad-spectrum antibiotics for sEONS.
Abstract
Broad-spectrum antibiotics for suspected early-onset neonatal sepsis (sEONS) may have pronounced effects on gut microbiome development and selection of antimicrobial resistance when administered in the first week of life, during the assembly phase of the neonatal microbiome. Here, 147 infants born at ≥36 weeks of gestational age, requiring broad-spectrum antibiotics for treatment of sEONS in their first week of life were randomized 1:1:1 to receive three commonly prescribed intravenous antibiotic combinations, namely penicillin + gentamicin, co-amoxiclav + gentamicin or amoxicillin + cefotaxime (ZEBRA study, Trial Register NL4882). Average antibiotic treatment duration was 48 hours. A subset of 80 non-antibiotic treated infants from a healthy birth cohort served as controls (MUIS study, Trial Register NL3821). Rectal swabs and/or faeces were collected before and immediately after treatment, and at 1, 4 and 12 months of life. Microbiota were characterized by 16S rRNA-based sequencing and a panel of 31 antimicrobial resistance genes was tested using targeted qPCR. Confirmatory shotgun metagenomic sequencing was executed on a subset of samples. The overall gut microbial community composition and antimicrobial resistance gene profile majorly shift directly following treatment (R2 = 9.5%, adjusted p-value = 0.001 and R2 = 7.5%, adjusted p-value = 0.001, respectively) and normalize over 12 months (R2 = 1.1%, adjusted p-value = 0.03 and R2 = 0.6%, adjusted p-value = 0.23, respectively). We find a decreased abundance of Bifidobacterium spp. and increased abundance of Klebsiella and Enterococcus spp. in the antibiotic treated infants compared to controls. Amoxicillin + cefotaxime shows the largest effects on both microbial community composition and antimicrobial resistance gene profile, whereas penicillin + gentamicin exhibits the least effects. These data suggest that the choice of empirical antibiotics is relevant for adverse ecological side-effects.
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Dynamics of gut microbiota during pregnancy in women with TPOAb-positive subclinical hypothyroidism: a prospective cohort study.
Wu, M, Chi, C, Yang, Y, Guo, S, Li, T, Gu, M, Zhang, T, Gao, H, Liu, R, Yin, C
BMC pregnancy and childbirth. 2022;22(1):592
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Subclinical hypothyroidism (SCH) in pregnancy refers to the elevation of thyroid stimulating hormone level with normal free T4 level. One third of women with SCH have been reported to test positive for anti-thyroid peroxidase antibody (TPOAb+). The aim of this study was to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. This study was a nested, prospective observational cohort study. A total of 64 and 68 pregnant women with TPOAb+ and TPOAb negative SCH, respectively, were included in this study. Results showed that women who were diagnosed with TPOAb+ SCH in trimester (T)1 show distinct dynamics of gut microbiota from T2 to T3. Furthermore, changes in the abundances of three types of bacterial species were abnormal in the presence of levothyroxine treatment. Authors conclude that gut microbiota can serve as potential therapeutic targets for TPOAb+ SCH during pregnancy.
Abstract
BACKGROUND Anti-thyroid peroxidase antibody (TPOAb) positivity can contribute to inhibit thyroxine synthesis. Gut microbiota can interact with metabolic or immune diseases. However, dynamics of gut microbiota from the second (T2) to the third trimester (T3) in women with TPOAb-positive/negative subclinical hypothyroidism (TPOAb+/TPOAb- SCH) have not been reported. Therefore, we aimed to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. METHODS In this single-center prospective cohort study, we observed gut microbiota dynamics by sequencing 16S rRNA from fecal samples collected in T2 (20-23+ 6 weeks) and T3 (28-33+ 6 weeks). TPOAb+/TPOAb- SCH were stratified depending on whether or not they used levothyroxine (LT4) during the pregnancy (LT4+/LT4-). Microbiome bioinformatics analyses were performed using QIIME2. The linear discriminant analysis effect size (LEfSe) was used for the quantitative analysis of biomarkers. Functional profiling was performed with PICRUSt2. RESULTS Distinct gut microbiota dynamics from T2 to T3 were noted in the TPOAb- (n = 68) and TPOAb+ (n = 64) SCH groups. The TPOAb+ LT4- group was characterized by enriched bacterial amplicon sequence variants (ASVs) of Prevotella in T2 and Bacteria, Lachnospirales, Lachnospiraceae, Blautia, and Agathobacter in T3 and by depleted ASVs of Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae in T2 and Actinobacteriota, Coriobacteriia, Actinobacteria, Coriobacteriales, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Dorea formicigenerans, and Bifidobacterium longum in T3. The TPOAb+ LT4+ group was characterized by enriched bacterial ASVs of Blautia, Streptococcus salivarius, and Bifidobacterium longum in T3 and by depleted ASVs of Bacteroidota, Bacteroidia, Bacteroidales, and Prevotella in T2 and Agathobacter in T3. Moreover, we identified 53 kinds of metabolic functions that were mainly involved in sugar, lipid, and amino acid metabolism. CONCLUSIONS Our results indicated that low dynamics of gut microbiota composition and high dynamics of its metabolic function from T2 to T3 were associated with TPOAb+ SCH. We concluded that gut microbiota could be new targets for treatment of TPOAb+ SCH during pregnancy. TRIAL REGISTRATION This study was retrospectively registered at the Chinese Clinical Trial Registry (registration number ChiCTR2100047175 ) on June 10, 2021.
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The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis.
Facondo, P, Di Lodovico, E, Delbarba, A, Anelli, V, Pezzaioli, LC, Filippini, E, Cappelli, C, Corona, G, Ferlin, A
Andrology. 2022;10(3):426-440
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The relationship between type 2 diabetes mellitus and male hypogonadism is well known, whereas the impact of type 1 diabetes mellitus (DM1) on male fertility and testis functions has been less studied. The aim of this study was to systematically review and discuss the available evidence evaluating paternity rate, male gonadal axis, and sperm parameters in men with DM1. This study is a systematic review and meta-analysis of fourteen studies. Results show: - reduced fertility potential in patients with DM1, as they have a lower number of children compared with unaffected population. In fact, the rate of children is statistically significantly lower among men who had been diagnosed with DM1 at an earlier age, according to a longer duration of the disease. - that men with DM1, compared with controls, have significantly lower normal sperm morphology, progressive motility and a trend toward a reduced semen volume, without difference in total sperm count and concentration. Authors conclude that DM1 might impair reproductive health at different levels, including functional sperm alterations definitively leading to reduced fertility rate in these patients.
Abstract
BACKGROUND Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear. OBJECTIVES To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1. MATERIALS AND METHODS A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta-analyzed. RESULTS The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta-analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [-0.36% (-0.66; -0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (-39.13; -28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [-0.51 (-1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto-antibodies, and retrograde ejaculation. DISCUSSION DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies. CONCLUSION Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions.