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Lifestyle-, environmental-, and additional health factors associated with an increased sperm DNA fragmentation: a systematic review and meta-analysis.
Szabó, A, Váncsa, S, Hegyi, P, Váradi, A, Forintos, A, Filipov, T, Ács, J, Ács, N, Szarvas, T, Nyirády, P, et al
Reproductive biology and endocrinology : RB&E. 2023;21(1):5
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The World Health Organization defines infertility as regular unprotected sexual intercourse without achieving conception within a year. In recent years, there has been a growing demand for functional, objective parameters reflecting fertility status more clearly than classical parameters. Of these, sperm DNA fragmentation (SDF) and the DNA fragmentation index – denoting the percentage of sperm with damaged DNA – seem to be of utmost importance. The aim of this study was to investigate all risk factors that may potentially be increasing SDF. This study is a systematic review and meta-analysis of one hundred and ninety articles. The earliest studies were published in 2003, and the latest in 2021. Results show that several modifiable risk factors negatively affect SDF, namely; a. health conditions: varicocele [when veins become enlarged inside the pouch of skin that holds the testicles] and impaired glucose tolerance, b. infections: Chlamydia, c. malignancies: testicular tumours, and d. lifestyle factors: smoking, alcohol consumption and body mass index. Authors conclude that several lifestyle-, environmental-, and additional health factors are associated with increased SDF.
Abstract
INTRODUCTION Infertility affects one in every six couples in developed countries, and approximately 50% is of male origin. In 2021, sperm DNA fragmentation (SDF) testing became an evidence-based test for fertility evaluations depicting fertility more clearly than standard semen parameters. Therefore, we aimed to summarize the potential prognostic factors of a higher SDF. METHODS We conducted a systematic search in three medical databases and included studies investigating any risk factors for SDF values. We calculated mean differences (MD) in SDF with 95% confidence interval (CI) for exposed and non-exposed individuals. RESULTS We included 190 studies in our analysis. In the group of associated health conditions, varicocele (MD = 13.62%, CI: 9.39-17.84) and impaired glucose tolerance (MD = 13.75%, CI: 6.99-20.51) had the most significant increase in SDF. Among malignancies, testicular tumors had the highest impact, with a maximum of MD = 11.3% (CI: 7.84-14.76). Among infections, the overall effects of both Chlamydia and HPV were negligible. Of lifestyle factors, smoking had the most disruptive effect on SDF - an increase of 9.19% (CI: 4.33-14.06). Different periods of sexual abstinence did not show significant variations in SDF values. Age seemed to have a more drastic effect on SDF from age 50 onwards, with a mean difference of 12.58% (CI: 7.31-17.86). Pollution also had a detrimental effect - 9.68% (CI: 6.85-12.52). CONCLUSION Of the above risk factors, varicocele, impaired glucose tolerance, testicular tumors, smoking, pollution, and paternal age of over 50 were associated with the highest SDF. TRIAL REGISTRATION CRD42021282533.
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The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review.
Zhang, T, Zhang, J, Duan, L
Nutrients. 2023;15(7)
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Inflammatory bowel disease (IBD), largely classified as Crohn’s disease (CD) or ulcerative colitis (UC), is a chronic intestinal inflammatory disorder mediated by genetic, immune, microbial, and environmental factors. The aim of this study was to summarise the efficacy of different genetically modified probiotics compared to wild-type probiotics in the treatment of IBD in animal models and patients and to investigate the specific effects and main mechanisms involved. This study was a systematic review of forty-five preclinical studies and one clinical study. Results showed a protective effect of genetically modified organisms (gm) probiotics in colitis. Several protective mechanisms have been identified: reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of the activity of oxidative stress in the colon, improvement of intestinal barrier integrity, modulation of the diversity and composition of gut microbiota, and production of favourable metabolites, including short-chain fatty acids, by beneficial bacteria. Authors concluded that gm probiotics are more effective and safer than wild-type probiotics, to facilitate clinical translation.
Expert Review
Conflicts of interest:
None
Take Home Message:
Conclusions of this review were largely based on mouse models and although treatment using probiotics is generally considered safe in humans, with only minor side-effects (flatulence), practitioners need to be aware that in an IBD population the use of GM formulations might not be completely without risk.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This paper summarises the efficacy of specific genetically modified (GM) probiotic formulations for Inflammatory Bowel Disease (IBD) when compared to wild type probiotics. The aim was to ascertain what specific effects and mechanisms such probiotics have on IBD symptomatology.
Methods
- A total of 46 published articles were included; 45 mouse experimental models (induced acute or chronic colitis) (n=15-130) and 1 human IBD population clinical trial (n=10)
- The effect of GM probiotics were compared to placebo and wild-type probiotics in trials including preclinical studies, randomised controlled trials and cohort studies
- Animals received probiotics via gastric gavage (105 - 4 x 1012 CFU) for 3-6 weeks
- The human placebo-uncontrolled trial lasted 7 days and patients received 10 GM capsules of L.lactis (1 x 1010 CFU) twice daily.
Results
- GM probiotics that secrete immunoregulatory cytokines such as IL-10 appear to reduce intestinal damage
- The human trial using GM L.lactis resulted in 5 patients who went into complete clinical remission (CDAI, <150) with 3 patients exhibiting a clinical response (decrease in CDAI, >70). with only minor adverse events (flatulence)
- However, human cytokines that promote intestinal barrier function and epithelial restitution were not enhanced with oral administration of probiotics
- Two studies concluded that GM L.lactis and S.boulardii, that secrete atrial natriuretic peptide, might be the most effective options in supporting colitis
- GM L.casei resulted in faster recovery from weight loss in acute colitis models
- Superoxide dismutase (SOD) producing GM L.fermentum increased SOD activity by almost eightfold compared to the wild type
- GM Lact. fermentum furthermore showed a higher survival rate and lower disease activity index (P <0·05) in colitis models
- GM L.lactis improved gut microbial composition and GM S.cerevisiae improved microbial diversity whilst reducing the Firmicutes to Bacteroides ratio
- GM E.coli significantly reduced weight loss, colon shortening plus lower disease activity and histological changes (P < 0.05).
Conclusion
Despite the heterogeneity of the trials, GM probiotics appear to play a notable part in ameliorating IBD symptomatology and disease severity when compared to wild-type probiotics. Human efficacy and potential adverse effects require more in-depth trials to ascertain safety and optimal dosages.
Clinical practice applications:
- Probiotics species used in the trials included S.thermophilus, E.coli, L.lactis, B.ovatus, S.boulardii, L.fermentum, B.longhum, L.casei, L.plantarum, and S.cerevisiae. Wild-types of some of these are already available to use in clinical practice
- Note that oral administration in the human trial showed no significant health outcome, therefore efficacy and safety need to be ascertained on an individual patient level
- Colonisation of beneficial bacteria in the gut of IBD patients might be difficult and any form of supplementation therefore needs to be closely monitored.
Considerations for future research:
- More evidence is needed to demonstrate that GM probiotic formulations result in significantly improved outcomes when compared to wild-types
- Future randomised placebo-controlled trials need to include larger cohorts to determine supplement efficacy
- Longer periods of intervention are needed to confirm efficacy, safety, and tolerance for both Crohn’s Disease and Colitis
- Optimal GM probiotic formulation, doses, and means of application need to be identified.
Abstract
BACKGROUND Many preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD). OBJECTIVE This systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms. METHODS PubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical. RESULTS Forty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn's disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients. CONCLUSIONS Gm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.
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SARS-CoV-2 effects on sperm parameters: a meta-analysis study.
Xie, Y, Mirzaei, M, Kahrizi, MS, Shabestari, AM, Riahi, SM, Farsimadan, M, Roviello, G
Journal of assisted reproduction and genetics. 2022;39(7):1555-1563
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Infertility is a reproductive system disorder. Viruses as a major cause of fertility problems can potentially interfere with reproductive function in men. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to be the causing viral pathogen of COVID-19 and capable of affecting human health. The aim of this study was to evaluate the effects of SARS-CoV-2 on different semen parameters including sperm count, sperm concentration, volume, motility, and progressive motility. This study is a meta-analysis of twelve studies of which seven were case control studies and five were retrospective cohort studies. Results show that SARS-CoV-2 infection could lead to significant impairments of male reproductive function through exerting negative influences on different semen parameters namely semen volume, sperm concentration, sperm count, and sperm motility. Authors conclude that their findings revealed the vulnerability of semen quality to SARS-CoV-2 infection.
Abstract
AIM: The rapid outbreak of the coronavirus disease 2019 (COVID-19) pandemic posed challenges across different medical fields, especially reproductive health, and gave rise to concerns regarding the effects of SARS-CoV-2 on male infertility, owing to the fact that the male reproductive system indicated to be extremely vulnerable to SARS-CoV-2 infection. Only a small number of studies have investigated the effects of SARS-CoV-2 on male reproduction, but the results are not consistent. So, we performed this meta-analysis to draw a clearer picture and evaluate the impacts of COVID-19 on male reproductive system. METHOD We searched Embase, Web of Science, PubMed, and Google Scholar databases to identify the potentially relevant studies. Standardized mean difference (SMD) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity testing, sensitivity analysis, and publication bias testing were also performed. RESULTS A total of twelve studies including 7 case control investigations and 5 retrospective cohort studies were found relevant and chosen for our research. Our result showed that different sperm parameters including semen volume [SMD = - 0.27 (- 0.46, - 1.48) (p = 0.00)], sperm concentration [SMD = - 0.41 (- 0.67, - 0.15) (p = 0.002)], sperm count [SMD = - 0.30 (- 0.44, - 0.17) (p = 0.00)], sperm motility [SMD = - 0.66 (- 0.98, - 0.33) (p = 0.00)], and progressive motility [SMD = - 0.35 (- 0.61, - 0.08) (p = 0.01)] were negatively influenced by SARS-CoV-2 infection. However, sperm concentration (p = 0.07) and progressive motility (p = 0.61) were not found to be significantly associated with SARS-CoV-2 infection in case control studies. No publication bias was detected. CONCLUSION The present study revealed the vulnerability of semen quality to SARS-CoV-2 infection. Our data showed a strong association of different sperm parameters with SARS-CoV-2 infection. The results suggested that SARS-CoV-2 infection in patients may negatively influence their fertility potential in a short-term period, but more studies are needed to decide about the long-term effects.
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Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies.
Sanchez-Gimenez, R, Ahmed-Khodja, W, Molina, Y, Peiró, OM, Bonet, G, Carrasquer, A, Fragkiadakis, GA, Bulló, M, Bardaji, A, Papandreou, C
Nutrients. 2022;14(13)
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Cardiovascular disease (CVD) remains a major public health issue. Identification of circulating biomarkers with prognostic value may help to both identify pathophysiological processes relevant to CVD development and improve preventive cardiovascular risk reduction efforts. The aim of this study was to identify the association of circulating levels of microbial metabolites with CVD incidence. This study is a systematic review of twenty-one studies of which 19 were prospective cohort studies, one study included one nested case-control study and one study included two nested case–control studies. Results show that: - associations of trimethylamine N-oxide (TMAO) [molecular metabolite derived from the gut flora] and subsequent risk of CV outcomes were supported by some but not all prospective studies. - inconsistent results were also obtained for secondary bile acids in relation to CVD and related outcomes, and CVD/all-cause mortality. - with regards to branched-chain amino acids (BCAAs), their associations with CV outcomes were robust amongst most of the studies. Authors conclude that their findings show inconsistent results for TMAO and bile acids but robust ones for the relationships between BCAAs and CVD. Thus, further studies are needed to investigate whether circulating microbial metabolites could be an intervention target for CVD.
Abstract
Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier's Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), tryptophan and indole derivatives, with risk of cardiovascular disease (CVD). A total of twenty-one studies were included in the systematic review after evaluating 1210 non-duplicate records. There were nineteen of the twenty-one studies that were cohort studies and two studies had a nested case-control design. All of the included studies were of high quality according to the "Newcastle-Ottawa Scale". TMAO was positively associated with adverse cardiovascular events and CVD/all-cause mortality in some, but not all of the included studies. Bile acids were associated with atrial fibrillation and CVD/all-cause mortality, but not with CVD. Positive associations were found between BCAAs and CVD, and between indole derivatives and major adverse cardiovascular events, while a negative association was reported between tryptophan and all-cause mortality. No studies examining the relationship between SCFAs and CVD risk were identified. Evidence from prospective studies included in the systematic review supports a role of microbial metabolites in CVD.
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Dietary macronutrients and the gut microbiome: a precision nutrition approach to improve cardiometabolic health.
Jardon, KM, Canfora, EE, Goossens, GH, Blaak, EE
Gut. 2022;71(6):1214-1226
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The global rise in the prevalence of obesity is strongly associated with an increase in the incidence and prevalence of cardiometabolic diseases, including insulin resistance (IR) and type 2 diabetes mellitus. In recent years, advancements have been made in understanding the involvement of the gut microbiome in obesity and related cardiometabolic complications as regulator of host energy and substrate metabolism. This study is a review that discusses the latest research describing interactions between dietary composition, the gut microbiome and host metabolism. Results show that current evidence for developing optimal dietary interventions targeting bodyweight control and IR via the gut microbiota is still in its infancy and does not capture the complexity of the integration of a whole-diet approach, the microbial and the host’s metabolic phenotype. Furthermore, implementation of targeted, precision nutrition intervention strategies or dietary guidelines for individuals or subgroups in public health requires further insight in the mechanisms involved in (non-)response to dietary intervention. Authors conclude that future studies are needed and these should focus on assessing detailed individual phenotyping and gaining insight into the balance between carbohydrate and protein fermentation by the gut microbiota as well as the site of fermentation in the colon.
Abstract
Accumulating evidence indicates that the gut microbiome is an important regulator of body weight, glucose and lipid metabolism, and inflammatory processes, and may thereby play a key role in the aetiology of obesity, insulin resistance and type 2 diabetes. Interindividual responsiveness to specific dietary interventions may be partially determined by differences in baseline gut microbiota composition and functionality between individuals with distinct metabolic phenotypes. However, the relationship between an individual's diet, gut microbiome and host metabolic phenotype is multidirectional and complex, yielding a challenge for practical implementation of targeted dietary guidelines. In this review, we discuss the latest research describing interactions between dietary composition, the gut microbiome and host metabolism. Furthermore, we describe how this knowledge can be integrated to develop precision-based nutritional strategies to improve bodyweight control and metabolic health in humans. Specifically, we will address that (1) insight in the role of the baseline gut microbial and metabolic phenotype in dietary intervention response may provide leads for precision-based nutritional strategies; that (2) the balance between carbohydrate and protein fermentation by the gut microbiota, as well as the site of fermentation in the colon, seems important determinants of host metabolism; and that (3) 'big data', including multiple omics and advanced modelling, are of undeniable importance in predicting (non-)response to dietary interventions. Clearly, detailed metabolic and microbial phenotyping in humans is necessary to better understand the link between diet, the gut microbiome and host metabolism, which is required to develop targeted dietary strategies and guidelines for different subgroups of the population.
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Psoriasis and cardiovascular disease risk in European and East Asian populations: evidence from meta-analysis and Mendelian randomization analysis.
Zhang, L, Wang, Y, Qiu, L, Wu, J
BMC medicine. 2022;20(1):421
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Psoriasis constitutes a chronic, inflammatory skin disease with an immune-genetic basis that has been linked to numerous diseases, including metabolic syndrome, cancer, as well as cardiovascular disease (CVD). The aim of this study was to determine if the relationship of psoriasis with CV events (CVE) risk is congruent with causal associations. This study is a report employing a meta-analysis of observational studies and a two-sample mendelian randomised trial (MR). Results from the meta-analysis show that psoriasis was remarkably associated with a higher risk of incident coronary artery disease (CAD) and myocardial infarction (MI) and was not associated with heart failure risk. Furthermore, the MR approach showed that psoriasis was linked with a higher risk of CAD in both European and East Asian populations. Additionally, psoriasis was also causally linked to an elevated risk of MI in European population. Authors conclude that their findings indicate a causal association of psoriasis with CAD and MI. However, further studies are needed to establish the mechanisms of the causal relationship of psoriasis with CAD and MI.
Abstract
BACKGROUND Psoriasis has been linked to cardiovascular disease (CVD), including coronary artery disease (CAD), myocardial infarction (MI), and heart failure (HF). However, available studies regarding this relationship have shown inconsistent results. Therefore, in this report, we performed a comprehensive review of the literature to assess the effects of psoriasis on risk of these CVDs. METHODS A search of literature until 24 December 2021 was done in PubMed, the Cochrane Library, Web of Science, Google Scholar, and Embase. Within European and East Asian populations, meta-analyses of observational studies assessing correlations between psoriasis and various CVD risk factors were conducted. Mendelian randomization (MR) was then employed to assess the causative impact of genetic pre-disposition for psoriasis on these CVD risk factors. RESULTS The results of the meta-analyses indicated that, in both the European and East Asian populations, psoriasis was significantly linked to an elevated risk in the incidence of CAD (RR = 1.51, 95% confidence interval (CI): 1.04-2.18, p = 0.028 and RR = 1.91, 95% CI: 1.62-2.25, p < 0.001) and MI (RR = 1.23, 95% CI: 1.04-1.46, p = 0.017 and RR = 2.17, 95% CI: 1.44-3.28, p < 0.001). A positive genetic relationship of psoriasis with CAD was found in European individuals (IVW OR1.03; 95% CI: 1.01-1.06, p = 0.005) and in East Asian individuals (IVW OR1.18; 95% CI: 1.03-1.32, p = 0.031). We also established that psoriasis was causally linked with an elevated risk of MI (IVW OR1.05; 95% CI: 1.01-1.09, p = 0.026) in the European population as determined using an MR approach. Moreover, our MR results were congruent with the null findings from the meta-analysis assessing associations of psoriasis with HF risk. CONCLUSIONS This research work provides preliminary evidence that psoriasis and CVD have a common genetic origin and that targeted psoriasis treatment might improve cardiovascular outcomes. These results not only increase our knowledge of the genetic underpinnings linking a comorbidity of psoriasis with CVD but also suggests a novel approach for CVD prevention.
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Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis.
Filippini, T, Wise, LA, Vinceti, M
Environment international. 2022;158:106920
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Cadmium is a toxic metal released in the environment after both natural and anthropogenic activities, particularly in contaminated and industrial areas devoted to smelting and refining of metals, and the manufacturing of batteries, coatings, or plastics. Exposure to cadmium may occur through occupational activities, smoking, food, and air pollution. The aim of this study was to provide updated literature on cadmium exposure and the risk of both type 2 diabetes and prediabetes, and to model the shape of these associations using a dose response approach. This study is a systematic review and meta-analysis of forty-two studies. Diabetes was investigated as an outcome in thirty-one studies, prediabetes in four studies, and both diabetes and prediabetes in seven studies. Results show that higher cadmium exposure was associated with increased risks of both diabetes and prediabetes. Diabetes risk increased linearly in studies using urinary cadmium concentrations, while disease risk increased only at the highest exposure levels when assessed using blood concentrations. The analysis for prediabetes also showed a linear increase in risk from low exposure, with a flattening effect at higher urinary cadmium concentrations. Authors conclude that their findings add to the available evidence on potential adverse health effects of environmental exposure to cadmium.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Cadmium exposure through diet, occupational exposure and smoking may increase the risk of type 2 diabetes in affected individuals.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Cadmium exposure might occur through occupational activities, food, air pollution, and smoking. Smokers, in particular, have higher blood cadmium concentrations than non-smokers. Food is the main transmission route for non-smokers, particularly cereals, vegetables, mollusks, and offal. Females and older adults are at a greater risk due to an increased risk of iron deficiency in these population groups, leading to increased absorption, as well as greater age-related bioaccumulation.
Furthermore, cadmium exposure has been associated with an increased risk of diabetes in a number of studies, as referenced in the present manuscript. However, the magnitude and shape of the correlation are uncertain.This systematic review and meta-analysis therefore investigates the relationship between exposure to cadmium and type 2 diabetes and prediabetes risk.
Methods
- The systematic review was conducted and reported in line with the PRISMA 2020 statement. Search strings related to the terms “cadmium” and “diabetes”, or “prediabetes state” in PubMed/MEDLINE, Web of Science and EMBASE databases were employed to search for relevant articles. Latest search date: 1 October 2021.
- Eligibility criteria included: studies evaluating cadmium exposure via biomarker levels with outcomes of interest being type 2 diabetes or prediabetes using WHO criteria and the American Diabetes Association; and reporting of relative risk estimates using the hazard ratio (HR), risk ratio (RR), or odds ratio (OR) with the corresponding 95% confidence interval (CIs). For inclusion in dose-response meta-analysis: reported effect estimates for all exposure categories along with dose in each category.
- Studies were assessed for risk of bias using theROBINS-E tool. Overall certainty of the evidence was assessed using the GRADE approach.
- The meta-analysis involved estimating RRs with corresponding 95% CIs from each study. Generalised least-squares regression with a random effects model and restricted maximum likelihood estimation were used. The highest versus lowest exposure categories were compared. The association between exposure and risk of diabetes or prediabetes was investigated using a one-stage dose-response meta-analysis. Sensitivity analyses were performed and heterogeneity between studies was assessed..
Results
- 42 eligible studies (case-control, cross-sectional, and cohort studies), ranging 65-34, 814 male and female adult participants, were identified investigating the association between cadmium exposure and risk of diabetes or prediabetes. Seven of the included studies were at overall high risk of bias; heterogeneity in the resulting meta-analyses was moderate to substantial. Sensitivity analyses indicated comparable results. Assessment with GRADE found no major inconsistency, indirectness or imprecision for either outcome.
- Comparing the highest versus lowest cadmium exposure concentrations associated with type 2 diabetes resulted in a RR of 1.24 (95% CI 0.96–1.59), RR 1.21 (CI 95% 1.00–1.45), and RR 1.47 (CI 95% 1.01–2.13) for blood, urinary, and toenail matrices, respectively. Concurrently, there was an elevated risk of prediabetes for cadmium levels in urine of RR 1.41 (95% CI: 1.15–1.73) and blood RR 1.38 (95% CI: 1.16–1.63), respectively.
- In the dose-response meta-analysis, a linear positive correlation between increasing urinary cadmium levels and diabetes risk was observed, with a RR 1.25 (95% CI 0.90–1.72) at concentration 2.0 µg/g of creatinine compared with no exposure. Conversely, for blood cadmium concentrations, the diabetes risk seemed to rise above 1 µg/L compared with no exposure. Moreover, prediabetes risk increased up to approximately 2 µg/g creatinine beyond which a plateau was reached with RR 1.40 (95% CI 1.12–1.76) at 2 µg/g creatinine.
- The meta-regression showed a negligible correlation between blood cadmium levels and diabetes risk. However, a positive yet imprecise association was found with increasing urinary cadmium concentrations. Similarly, no association was observed between blood cadmium concentrations and risk of prediabetes, whereas a positive relationship with urinary cadmium levels was observed. However, these findings were based on a limited cohort of studies.
Conclusions
- A positive linear correlation between cadmium concentration (measured in multiple matrices) and risk of both type 2 diabetes and prediabetes with a dose-response relationship (moderate-certainty evidence) were observed in this systematic review and meta-analysis. Diabetes risk increased linearly in studies using urinary cadmium concentrations, whereas disease risk increased only at the highest exposure levels when assessed using blood levels. The analysis for prediabetes also demonstrated a linear increase in risk from low exposure, which plateaued at higher urinary cadmium concentrations.
Clinical practice applications:
- To inform practitioners and clients of the risks of cadmium exposure in the diet, through occupational exposure, and through smoking.
- To motivate practitioners to educate themselves and their clients regarding the foods which may pose a higher risk of cadmium exposure (not reviewed in the present article).
- To advise clients on prediabetes and type 2 diabetes risk from cadmium exposure through smoking.
Considerations for future research:
- As cited by the authors, future studies could incorporate stratified analysis in specific subgroups, e.g., non-smokers, or could be restricted to prospective cohort studies with more sufficient data,
- Large-scale observational studies could be conducted investigating cadmium exposure in smokers versus non-smokers.
- Clinical trials could be performed to evaluate the effect of reduction or cessation of tobacco smoking on total body cadmium concentrations .
- Continuous surveillance of dietary cadmium exposure and other heavy metals should be prioritised to inform public health.
- Dietary interventions could assess the possibility to attenuate the risk of cadmium exposure.
Abstract
BACKGROUND Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association. OBJECTIVE To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association. DATA SOURCE After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes. STUDY ELIGIBILITY CRITERIA We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only. STUDY APPRAISAL AND SYNTHESIS METHODS Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model. RESULTS In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine. LIMITATIONS AND CONCLUSIONS This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.
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Interaction of cervical microbiome with epigenome of epithelial cells: Significance of inflammation to primary healthcare.
Holubekova, V, Kolkova, Z, Kasubova, I, Samec, M, Mazurakova, A, Koklesova, L, Kubatka, P, Rokos, T, Kozubik, E, Biringer, K, et al
Biomolecular concepts. 2022;13(1):61-80
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A female health is one medical area of the framework strategies in predictive, preventive, and personalized (3P) medicine. Cervical cancer is preventable and successfully treatable at early stages that makes the disease as an ideal candidate applicable in the context of 3P medicine. The aim of this study was to examine the interaction of the cervical microbiome with epithelial cells in relation to inflammation, and to assess direct evidence of epigenetic changes related to the cervical microbiome. This study is a systematic review of publications in the field of cervical cancer research. This review shows that: - cervical cancer screening in future integration of precision cancer prevention regimes should match an individual’s risk of cancer in context with genomic and environmental factors. - identification of microbiome population might be one of the key aspects of precision medicine in the future. Microbial composition may early identify the potential risk of precancerous lesion formation or permanent bacterial vaginosis. - the composition of the microbiome can be influenced by dietary composition, which will also affect the epigenetic background of the microbiome. However, food forms the microbiome through epigenetic mechanisms, and it is thus necessary to clarify how cancer risk is increased due to food-related microbially produced metabolites. - an examination of the metabolites during inflammation of the cervical epithelium and bacterial vaginosis may improve the precise identification of inflammatory-induced biomarkers that could aid in the precision medicine in prediction of the risk of cervical dysplasia development. - cancer-associated inflammation pathways can be influenced by phytochemicals with anti-inflammatory effects on immune cells, suppression of proinflammatory transcription factors, cytokines, and chemokines. The biological balance between uncontrolled chronic inflammation and controlled inflammation is essential for cancer prevention, prediction, and prognostication. Authors conclude that their review highlighted the pivotal contribution of cervical microbiome, epigenetic changes, and inflammation to the formation of cervical intraepithelial lesion and progression to cervical cancer.
Abstract
One pillar of the predictive, preventive, and personalized medicine framework strategies is the female health. The evaluation of women's lifestyle and dietary habits in context with genetic and modifiable risk factors may reflect the prevention of cervical cancer before the occurrence of clinical symptoms and prediction of cervical lesion behavior. The main aim of this review is to analyze publications in the field of precision medicine that allow the use of research knowledge of cervical microbiome, epigenetic modifications, and inflammation in potential application in clinical practice. Personalized approach in evaluating patient's risk of future development of cervical abnormality should consider the biomarkers of the local microenvironment characterized by the microbial composition, epigenetic pattern of cervical epithelium, and presence of chronic inflammation. Novel sequencing techniques enable a more detailed characterization of actual state in cervical epithelium. Better understanding of all changes in multiomics level enables a better assessment of disease prognosis and selects the eligible targeted therapy in personalized medicine. Restoring of healthy vaginal microflora and reversing the outbreak of cervical abnormality can be also achieved by dietary habits as well as uptake of prebiotics, probiotics, synbiotics, microbial transplantation, and others.
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9.
Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID.
Stefano, GB
Medical science monitor : international medical journal of experimental and clinical research. 2021;27:e931447
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Literature shows that there are long-term symptoms and organ damage in patients with confirmed coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 that persist after the acute illness. The aim of this review was to present a historical overview of infections and disorders associated with the neurological and psychiatric sequelae that have shown similarities with long COVID. Historically, the common symptom of altered cognition has been reported during earlier pandemics. Pandemics discussed in this review include; influenza pandemics of 1889 and 1892 (Russian flu), Spanish flu pandemic (1918-1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome). Furthermore, literature shows that there are similarities between the symptoms of chronic fatigue syndrome and the brain fog of long COVID. Viral infection, cerebral hypoxia [reduced supply of oxygen to the brain), cognitive dysfunction, or brain fog may occur along a common pathway in the long-term pathogenesis of epidemic and pandemic infections, including COVID-19. Authors conclude that utilising data from past epidemics and pandemics may help to identify common acute and chronic syndromes, including neurological and psychiatric sequelae with similarities to the conditions currently described in patients with long COVID.
Abstract
Long-term sequelae of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized. However, there is still a lack of consensus regarding the terminology for this emerging chronic clinical syndrome, which includes long COVID, chronic COVID syndrome, post-COVID-19 syndrome, post-acute COVID-19, and long-hauler COVID-19. In this review, I will use the term "long COVID". A review of the medical history and epidemiology of past pandemics and epidemics in modern literature review identifies common long-term post-infectious disorders, with the common finding of altered cognition. In the brain, the cerebral hypoxia induced by SARS-CoV-2 infection may be caused by mitochondrial dysfunction, resulting in "brain fog". Historically, the common symptom of altered cognition has been reported during earlier pandemics, which include the influenza pandemics of 1889 and 1892 (Russian flu), the Spanish flu pandemic (1918-1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome). There are similarities between chronic fatigue syndrome and the "brain fog" described in long COVID. During past viral epidemics and pandemics, a commonality of neural targets may have increased viral survival by conformational matching. The neurological and psychiatric sequelae of SARS-CoV-2 infection, or long COVID, may have emerged from neural effects that have emerged from an invertebrate and vertebrate virosphere. This review aims to present a historical overview of infections and disorders associated with neurological and psychiatric sequelae that have shown similarities with long COVID.
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10.
SARS-CoV-2 and immune-microbiome interactions: Lessons from respiratory viral infections.
Cyprian, F, Sohail, MU, Abdelhafez, I, Salman, S, Attique, Z, Kamareddine, L, Al-Asmakh, M
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021;105:540-550
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus. This virus caused the coronavirus disease 2019 (COVID-19) pandemic. The aim of this review was to investigate the relationship between microbiota, immunity, and COVID-19, with particular focus on how microbiome-associated immune crosstalk can shape outcome of COVID-19. The study included 118 articles which investigated or reviewed COVID-19 or coronavirus and the microbiome of the gut or respiratory tract. Findings indicate that: - an over-activated immune system leads to massive pulmonary damage in COVID-19 patients. - the effect of aging and comorbidities, and the use of antibiotics have an effect on the diversity of the microbiota. - the milieu of gut flora can exert influence on pulmonary immune responses. - a unique cross-talk exists between the pulmonary and gut microbial compartments. Authors conclude by highlighting the need of further studies that delineate the role of the microbiota and their products in the immune dysregulation observed in SARS-CoV-2 infections.
Abstract
By the beginning of 2020, infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had rapidly evolved into an emergent worldwide pandemic, an outbreak whose unprecedented consequences highlighted many existing flaws within public healthcare systems across the world. While coronavirus disease 2019 (COVID-19) is bestowed with a broad spectrum of clinical manifestations, involving the vital organs, the respiratory system transpires as the main route of entry for SARS-CoV-2, with the lungs being its primary target. Of those infected, up to 20% require hospitalization on account of severity, while the majority of patients are either asymptomatic or exhibit mild symptoms. Exacerbation in the disease severity and complications of COVID-19 infection have been associated with multiple comorbidities, including hypertension, diabetes mellitus, cardiovascular disorders, cancer, and chronic lung disease. Interestingly, a recent body of evidence indicated the pulmonary and gut microbiomes as potential modulators for altering the course of COVID-19, potentially via the microbiome-immune system axis. While the relative concordance between microbes and immunity has yet to be fully elucidated with regards to COVID-19, we present an overview of our current understanding of COVID-19-microbiome-immune cross talk and discuss the potential contributions of microbiome-related immunity to SARS-CoV-2 pathogenesis and COVID-19 disease progression.