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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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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 effectiveness of interventions during the first 1,000 days to improve energy balance-related behaviors or prevent overweight/obesity in children from socio-economically disadvantaged families of high-income countries: a systematic review.
Lioret, S, Harrar, F, Boccia, D, Hesketh, KD, Kuswara, K, Van Baaren, C, Maritano, S, Charles, MA, Heude, B, Laws, R
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;24(1):e13524
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The first 1,000 days is an opportune time to support parents, as primary caregivers and role model, to promote a healthy lifestyle and prevent obesity for their children. The aim of this study was to update the current evidence on the effectiveness of family-based interventions implemented during pregnancy and up to 2 years of age to improve energy balance-related behaviours and growth, or prevent overweight (OW)/ obesity (OB), in children growing up in families experiencing socio-economic disadvantage. This study is a systematic review of thirty-three studies which corresponded to 24 distinct interventions. Of the 24 interventions, nearly all were (cluster) randomised controlled trials; three had a quasi-experimental design. Results show that there is some effectiveness on behavioural and anthropometric outcomes in young children when programmes target and are tailored to families experiencing socioeconomic disadvantage. Authors conclude that a holistic, multilevel and proportionate interventions are likely to more effective and sustainably address the issue of social inequalities and inequities. Additionally, more thorough process evaluation of such complex interventions using mixed methods is needed to better understand why interventions worked or not, by which mechanisms of action (if any), for whom and in which context.
Abstract
This narrative systematic review examined effectiveness of interventions during pregnancy and up to 2 years of age in improving energy balance-related behaviors or prevent overweight/obesity in children from families experiencing socio-economic disadvantage. We identified 24 interventions, from 33 articles, since 1990. Overall, despite their heterogeneity and variability in internal and external validity, there was some evidence of beneficial impact of interventions on obesity risk (4/15), and associated behaviors, e.g.: breastfeeding (9/18), responsive feeding (11/16), diet (7/8), sedentary (1/3) and movement (4/7) behaviors, and sleep (1/2). The most effective interventions aimed at promoting breastfeeding commenced antenatally; this was similar for the prevention of obesity, provided the intervention continued for at least 2 years postnatally and was multi-behavioral. Effective interventions were more likely to target first-time mothers and involve professional delivery agents, multidisciplinary teams and peer groups. Among ethnic/racial minorities, interventions delivered by lay agents had some impact on dietary behavior but not weight outcomes. Co-creation with stakeholders, including parents, and adherence to theoretical frameworks were additional ingredients for more pragmatic, inclusive, non-judgmental, and effective programs. The growing body of evidence on obesity prevention interventions targeting families experiencing socio-economic disadvantage is promising for reducing early inequalities in obesity risk.
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Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies.
Chávez-Hidalgo, LP, Martín-Fernández-de-Labastida, S, M de Pancorbo, M, Arroyo-Izaga, M
World journal of gastroenterology. 2023;29(7):1219-1234
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Colorectal cancer (CRC) is the third most frequent type of cancer and yet has the second highest mortality rate in cancer patients worldwide. Hence there is an urgency to understand more about dietary and lifestyle factors that can help to prevent this type of cancer. It is known that folate has a preventive function in CRC, possibly due to its role in DNA methylation. Methylation is the addition of methyl groups to DNA, which influences gene expression and regulation. This systematic review investigated how folate and other dietary methyl groups and methyl influencers such as B vitamins and alcohol influence the development of CRC, whilst also considering various genetic variants in methyl-metabolising enzymes (polymorphisms). The analysis included a total of 19 case-control and cohort studies and highlighted that potential interactions between methyl donor nutrients, genetic variants, and alcohol influence CRC risk. For most, high levels of folate intake were considered a protective factor, while high alcohol consumption proved to be a risk factor. Yet these interactions appear to be complex, with gender, genetic variations and folate status appearing to contribute to variable and, in some cases, contradictory outcomes. The authors suggested in their findings that Vitamin B6, Vitamin B3 (Niacin), and alcohol may affect CRC by influencing its risk by acting on both the genetic code itself and the epigenetic factors that control gene activity. Further research is needed to better understand the complexity of these mechanisms, and to help clarify the influence of methyl group donors as epigenetic regulators of gene activity in CRC development.
Abstract
BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. AIM: To improve the current understanding of the molecular basis of CRC. METHODS A literature search in the Medline database, Reference Citation Analysis (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022. RESULTS A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk. CONCLUSION Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B6, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.
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Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
Oh, JH, Jang, YS, Kang, D, Kim, HS, Kim, EJ, Park, SY, Kim, CH, Min, YW, Chang, DK
Gut and liver. 2023;17(1):100-107
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Irritable bowel syndrome (IBS) affects 1 in 10 people globally and is a common health problem for the elderly. Recent studies have shown that changes in the gut microbiome may play an important part in IBS and there is evidence that using pre and pro biotics have positive effects on IBS. The aim of this randomized, double-blind, placebo-controlled trial was to determine the effects of a new synbiotic formulation (L. paracasei DKGF1 and prebiotics extracted from O. humifusa) on GI symptoms in elderly patients with IBS. 67 participants were randomly divided into 2 groups. For 4 weeks one group took the synbiotic and the other group took a placebo. Symptoms were recorded via questionnaires. The consumption of the synbiotic combination was associated with overall relief of IBS symptoms in elderly patients. In particular, abdominal pain and psychological well-being noticeably improved. In conclusion this synbiotic is effective and safe to use in elderly patients with global IBS symptoms.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The management of IBS in elderly people is more complicated than in younger populations.
- Synbiotic formulations containing both probiotics and prebiotics have reported gastrointestinal health benefits.
- This randomized controlled trial indicated that the synbiotic containing L. paracasei DKGF1 and Optuntia humifusa extracts might be effective and safe for treating IBS symptoms in elderly patients.
Evidence Category:
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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:
This study involved a randomized, double-blind, placebo-controlled trial to investigate the impact of a synbiotic combination, comprising of L. paracasei DKGF1 and prebiotics extracted from Optuntia humifusa, on Irritable Bowel Syndrome (IBS) in elderly patients.
Method
Sixty-seven IBS patients (mean age: 64 years) were randomly assigned to either a synbiotic group (n=33) or a placebo group (n=34) for a 4-week intervention. The synbiotic group received a daily sachet containing one billion colony-forming units of L. paracasei DKGF1, 0.2g of O. humifusa extract and 1.59 grams of maltodextrin, while the placebo group received an identical sachet containing only maltodextrin.
During the study period
- Participants recorded the degree of symptom improvement using a Subject Global Assessment (SGA) scale.
- IBS symptoms, abdominal pain, gas, bloating, and psychological well-being were recorded using a Visual Analogue Scale (VAS).
- Stool form and consistency were assessed using a Bristol Stool Chart (BSC).
Results
The primary findings from the study were as follows:
- There was significant improvement in IBS symptoms as measured by the SGA score, in the synbiotic group versus the placebo group (+50.5% vs +23.5%, p=0.017). The synbiotic group consistently demonstrated improved response rates.
The secondary findings were as follows:
- Participants also reported an improvement in psychological well-being in the synbiotic group (from 1.3 to 1.0) compared to the placebo group (from 3.0 to 2.0) (p=0.003).
- Responders reported a significant improvement in stool form and consistency in the synbiotic group (+85.7%) compared to the placebo group (+22.2%) (p=0.04).
- Among the patients with IBS constipation, patients in the synbiotic group reported a positive response compared to the placebo group (0% and +100%, p=0.029).
- . However, there was no significant improvement among the patients with IBS diarrhoea in the synbiotic group compared to the placebo group (+33.3% and +66.6%,, p=0.52).
Conclusion:
This randomized, double-blind, placebo-controlled trial, reported that the synbiotic combination of L. paracasei DKGF1 and Optuntia humifusa, may be associated with the relief of IBS symptoms in elderly patients, particularly in terms of abdominal pain and psychological well-being.
Clinical practice applications:
- The human microbiota undergoes changes in diversity and variation with age, emphasising the importance of understanding age-specific interventions.
- Managing IBS in the elderly is challenging, and synbiotics, containing both probiotics and prebiotics, have reported gastrointestinal health benefits.
- Most clinical trials have excluded elderly patients, and there has been uncertainty about whether synbiotic use is safe for the elderly.
- This study focused exclusively on elderly patients with IBS, indicating the potential safety and effective use of a synbiotic containing L. paracasei DKGF1 and Optuntia humifusa in improving IBS symptoms.
Considerations for future research:
- Only elderly patients were included in this study, therefore further investigation is needed to explore the effects of synbiotics on participants of different age groups.
- Microbial analysis was not done in this study. It would be useful to include this in future research to gain more insight into the microbiome’s diversity in elderly patients with IBS.
- The study did not quantify food intake or variety which might have impacted the results, therefore future research needs to consider the impact diet has on the microbiome and IBS.
- Since patient reports are subjective, future research should consider involving researchers during patient-reported assessments to enhance the accuracy and reliability of the data.
Abstract
BACKGROUND/AIMS: There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS. METHODS Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebo group (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4. RESULTS Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological well-being (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group. CONCLUSIONS The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.
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Effects of a Raisin Supplement on Cognitive Performance, Quality of Life, and Functional Activities in Healthy Older Adults-Randomized Clinical Trial.
Rodrigo-Gonzalo, MJ, González-Manzano, S, Pablos-Hernández, MC, Méndez-Sánchez, R, Ayuda Duran, B, González-Sánchez, J, Barbero-Iglesias, F, González-Paramás, AM, Recio-Rodríguez, JI
Nutrients. 2023;15(12)
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The regular intake of foods rich in polyphenols shows many biological activities, such as antioxidant, cardioprotective, anti-inflammation and anti-aging properties. This diversity of compounds found in grapes, especially red grapes, makes it a candidate for testing the role of dietary polyphenols to health. The objective of this single blinded randomised controlled clinical trial was to evaluate the effects of consuming 50g of Málaga muscatel raisins which are dried grapes on cognitive performance, quality of life, and functional activities in healthy adults over 70 years. According to the researchers this is the first study looking at the effect of raisins on cognitive performance. A group of 80 participants were split into two groups with one group adding 50g of raisins a day to their usual diet for six months and a control group of 40 patients receiving no raisins. Cognitive performance was measured by various tests which are summarised in the full text article. The results of this study showed that the supplement of 50 g of raisins slightly improved cognitive performance including spatial orientation, memory and comprehension, reading, writing, and drawing. In addition to a slight improvement in quality of life and functional activities. This shows promising results and that the addition of raisins to the diet along with a variety of foods rich in polyphenols can confer positive health benefits that can prevent age related cognitive decline. More research is needed to know exactly the mechanism of action of polyphenols on cognitive performance.
Abstract
The objective of this study was to evaluate the effects of consuming 50 g of raisins on cognitive performance, quality of life, and functional activities in healthy older adults. This is a parallel randomized controlled clinical trial, in which 80 subjects over 70 years of age participated. For 6 months, the intervention group (IG; n = 40) consumed 50 g of raisins per day added to their usual diet, whereas the control group (CG; n = 40) received no supplement. All variables were measured at baseline and at 6 months. Cognitive performance assessed with the Montreal Cognitive Assessment (MOCA) test shows a difference of 3.27 points (95% CI 1.59 to 4.96), p ≤ 0.001, favorable to the IG, after the intervention. Among the cognitive performances, an improvement is observed in the IG in orientation, assessed both with the MOCA test 0.49 (95% CI 0.10 to 0.87), p = 0.014, and with the Mini-Mental State Examination (MMSE) test, 0.36 (95% CI 0.02 to 0.70), p = 0.038. In visuospatial/executive capacity and in language, improvements were also observed in the IG, 1.36 (95% CI 0.77 to 1.95), p = 0.001, and 0.54 points (95% CI 0.12 to 0.96), p = 0.014, respectively. Immediate and delayed recall, assessed with the Rey Auditory Verbal Learning Test, improved in the IG. In addition, the IG showed a better quality of life and greater autonomy in instrumental activities of daily living after 6 months. No significant changes were observed in the rest of the variables analyzed. Therefore, the consumption of 50 g of raisins produces a slight improvement in cognitive performance, quality of life, and functional activities in the elderly.
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Diet as an Optional Treatment in Adults With Inflammatory Bowel Disease: A Systematic Review of the Literature.
Jaramillo, AP, Abaza, A, Sid Idris, F, Anis, H, Vahora, I, Moparthi, KP, Al Rushaidi, MT, Muddam, M, Obajeun, OA
Cureus. 2023;15(7):e42057
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Crohn's disease (CD) and ulcerative colitis (UC) are linked with significant morbidity and higher healthcare costs. The current model of CD pathogenesis implies that environmental variables and the gut microbiota interact in those who are genetically predisposed to the condition. The aim of this study was to investigate a treatment based on the diet of IBD patients. This study was a systematic review of nine studies. Results showed that following a diet that reduces inflammation may prevent its recurrence in UC patients in clinical remission. In fact, there were significant systemic changes in the intestinal microbiota of anti-inflammatory diet patients. Authors concluded that a four-week FODMAP diet combined with professional counseling and regular follow-up will be helpful in the therapy of persistent gastrointestinal symptoms in quiescent IBD, although care should be used in the long run.
Expert Review
Conflicts of interest:
None
Take Home Message:
Whilst concise, this limited review highlights the current lack of evidence supporting stand alone dietary strategies in preventing relapse for IBD patients. At the very least an anti-inflammatory diet should ideally be implemented alongside specific medical care and counselling to minimise risk of disease relapses.
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 systematic review evaluated the efficacy of diet as a preventative therapeutic treatment for Inflammatory Bowel Disease (IBD).
Methods
A total of 9 studies (published in the last 5 years) were chosen. The articles included 6 randomised controlled trials (RCT), one systematic literature review (SLR) and two SLR and meta-analysis. The authors used the Assessment Systematic Reviews (AMSTAR) approach and an unspecified Cochrane Risk of Bias assessment tool.
Results
(The following refers to the original RCT articles as the review article data was sparse).
- A 6-month, open-label, randomised, placebo-controlled trial of 53 adult Ulcerative Colitis (UC) patients compared response to an Anti-inflammatory Diet (AID) with Canada’s Food Guide (CFG). The outcome showed that the faecal calprotectin value (<150 µg/g at the endpoint) was significantly higher in the AID group (69.2 vs. 37.0%, p = 0.02) (Keshteli et al., 2022).
- The Specific Carbohydrate Diet (SCD) was not superior to the Mediterranean Diet (MD) in terms of achieved symptomatic remission at 6 weeks (SCD 46.5%, MD 43.5%; p = .77) (Lewis et al., 2022).
- A single-blind, 4-week trial concluded significant relief from gut symptoms was achieved when comparing a low FODMAP diet (14/27, 52% of positive patient feedback) to a control diet (4/25, 16%, p=.007) (Cox et al., 2020).
- A 7-day trial of 28 volunteers compared individualised food-based diet (CD-TREAT), with similar composition to Exclusive Enteral Nutrition (EEN) and found a change in relative abundance in faecal microbiome genera of 58 (49.3%) and 38 (32.3%) following both feeding practices respectively (Svolos et al., 2019).
- Substantial reduction in red and processed meat was not significant in reducing time to symptomatic relapse in Crohn’s Disease (CD) patients when comparing 115 high red meat consumers with 87 low red meat CD patients (p = 0.61 any relapse and p = 0.50 for moderate to severe relapse) (Aldenberg et al., 2019).
Conclusion
An anti-inflammatory diet may prolong clinical remission for UC patients. CD patients, with mild to severe symptoms, may tolerate both the MD and SCD equally well. The authors advise a low FODMAP diet for a 4-week period combined with professional counselling and regular follow-up sessions to delay flare-up episodes. However the findings were based on a very limited number of scientific material that requires extensive further assessment prior to deriving any firm conclusions.
Clinical practice applications:
- In order to delay relapse in IBD it is imperative that foods that support anti-inflammatory mechanisms are incorporated and maintained
- Whilst limited, the papers reviewed highlight potential for an initial low FODMAP diet followed by a longer term MD or SCD combined with constant monitoring
- From one study, red meat consumption did not appear to exacerbate symptoms.
Considerations for future research:
- Future studies need to include larger cohorts to ascertain the efficacy of dietary interventions as a stand alone treatment option for IBD
- Longer periods of intervention are needed to confirm dietary intervention efficacy and safety in this population.
Abstract
While the exact cause of IBD is unknown, there are a number of factors that are thought to contribute to its development, including environmental and genetic factors. While exclusive enteral nutrition (EEN) is a promising therapy for Crohn's disease (CD), it is not yet considered a first-line treatment. Additionally, the efficacy of EEN compared to corticosteroid treatment is still being investigated. EEN is suggested as a first-line therapy by which guidelines and in which age groups, as it may differ in pediatric and adult recommendations. Another finding was that dietary changes involving an increase in anti-inflammatory foods and decreased intake of foods high in inflammatory compounds are linked to a beneficial outcome both metabolically and microbiologically in patients with ulcerative colitis (UC) in remission. For relevant medical literature, we examined PubMed/Medline, the Cochrane Library, and Google Scholar as examples of medical databases. The articles were identified, evaluated, and eligibility applied, and nine publications were found. The finished articles investigated the role of several diet alternatives for patients with IBD. Some others have shown that following a normal low-fat diet may be effective in reducing the occurrence of subclinical colitis. The EEN and partial enteral nutrition (PEN) indicated no significant differences between both regimens, but both had good outcomes during active IBD. Other strict diets, such as the specific carbohydrate diet (SCD) versus the Mediterranean diet (MD), demonstrate excellent outcomes in patients with IBD. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) dietary counseling improves gastrointestinal symptoms and quality of life in IBD patients. Based on the above, we concluded that more studies determining which component of the diet is not clear (proteins, carbs balanced) or diet types are required to establish a particular diet employed as a treatment intervention in these individuals.
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8.
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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9.
Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.
Wang, YB, Yang, L, Deng, YQ, Yan, SY, Luo, LS, Chen, P, Zeng, XT
Journal of translational medicine. 2022;20(1):495
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Benign prostatic hyperplasia (BPH) is a common benign disease in middle-aged and elderly men which is often underestimated and underdiagnosed. If patients are not treated in time, it may lead to serious complications, such as urinary retention, renal insufficiency and renal failure. The aim of this study was to evaluate the possible causal associations of abdominal obesity (measured as waist circumference), overall obesity (measured as body mass index), lifestyle factors (dietary habits, smoking, alcohol drinking, and sedentary behaviour) with risk of BPH. This study is a univariable and multivariable mendelian randomised study. Results show that genetic predisposition to higher waist circumference and sedentary behaviour are independently and causally associated with the risk of BPH. However, there isn’t conclusive evidence that genetic predisposition to relative carbohydrate, fat, protein, and sugar intake, smoking and alcohol drinking are causally associated with the risk of BPH. Authors conclude that further studies are needed to identify comprehensive risk factors on BPH and develop freely accessible prediction models for the BPH. These will help to identify individuals at particular risk and provide decision-making supports for individualised intervention.
Abstract
BACKGROUND Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. METHODS We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis. RESULTS The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI. CONCLUSION This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.
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10.
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.