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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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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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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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The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis.
Gudnadottir, U, Debelius, JW, Du, J, Hugerth, LW, Danielsson, H, Schuppe-Koistinen, I, Fransson, E, Brusselaers, N
Scientific reports. 2022;12(1):7926
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Preterm birth is a major cause of neonatal mortality and morbidity. Many factors can trigger premature labour onset, including preterm premature rupture of membranes, infections and microbial invasion of the amniotic cavity. The vaginal microbiome is thought to protect from such infections. The aim of this study was to assess the association between the vaginal microbiome and the risk of preterm birth. This study is a systematic review and meta-analysis of 17 cohort studies. The number of pregnancies per study ranged between 38 and 539, with 8 and 107 preterm births. Results show that women with a “low-lactobacilli” vaginal microbiome composition were at higher risk of preterm birth (spontaneous and overall) compared to women with L. crispatus (microbiome) dominant microbiome compositions. Authors conclude that the diversity of the vaginal microbiome seems to play a part in the risk of preterm birth.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The diversity of the vaginal microbiome is reported to play a part in the risk of preterm births.
- Practitioners could consider testing the virginal microbiome for low Lactobacilli or the dominance of Gardnerella and Prevotella and then recommending a probiotic supplement to pregnant patients who have low Lactobacilli vaginal microbiome.
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
A systematic review and network meta-analysis was conducted to investigate the association between vaginal microbiome and risk of preterm births.
Methodology
- Seventeen longitudinal cohort studies were included. Seven originated from North America, three from Europe, two from South America, three from Asia, and two from Africa. The number of pregnancies per study ranged between 38 and 539, with 8 and 107 preterm births. 16S Sequencing techniques were used to identify the microbial species. Preterm birth was defined as birth before 37 weeks of gestation.
- Microbiome community state types (CSTs) were grouped into five categories based on dominating species: L. crispatus, L. gasseri, L. iners,“low-lactobacilli” and L. jensenii. “Low-lactobacilli” was defined as an increased diversity of anaerobic or mixture of aerobe and facultative anaerobe bacteria (such as Gardnerella and Prevotella) based on the cut-offs and categorization used in the individual studies.
Results
Primary clinical outcomes were:
- Among women who delivered preterm, the pooled proportion with “low-lactobacilli” was 0.41 (95% CI 0.30-0.53) compared to 0.29 (95% CI 0.20-0.38) of women with full-term deliveries.
- The risk of preterm births was higher among women with “low-lactobacilli” compared to L. crispatus (OR 1.69, 95%CI 1.15 -2.49).”Low-lactobacilli” included Garnerella and Provotella, both of which are known to promote inflammatory cytokines and are commonly found in vaginal microbiome just before preterm premature rupture of membranes (PPROM).
Clinical practice applications:
- The diversity of the vaginal microbiome is reported to play an important role in the risk of preterm births.
- Women with low Lactobacilli seem to be at a greater risk of delivering preterm compared to women with L. crispatus dominant microbiome.
- Based on this study, practitioners could therefore consider testing the vaginal microbiome of their patients for low Lactobacilli and/or the dominance of Gardnerella and Prevotella.
- Practitioners may also consider recommending specific probiotic supplementation during pregnancy to increase the dominance of Lactobacilli and L. crispatus vaginal microbiome.
Considerations for future research:
- In the past, researchers have grouped the microbiome into categories based on dominating species, which is not ideal. Therefore, further studies are needed where individual microbiome sequencing data is used to make comparisons.
- Additionally, longitudinal studies are needed with higher sample sizes to investigate the natural changes of the vaginal microbiome during pregnancy and the physiological mechanisms underlying these apparent different risk profiles.
- Furthermore, randomized-controlled trials are needed to establish if pregnant women could benefit from specific probiotic supplementation during pregnancy.
Abstract
Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour that leads to preterm birth. The aim of this systematic review and network meta-analysis was to investigate the association between the vaginal microbiome, defined as community state types (CSTs, i.e. dominance of specific lactobacilli spp, or not (low-lactobacilli)), and the risk of preterm birth. Systematic review using PubMed, Web of Science, Embase and Cochrane library was performed. Longitudinal studies using culture-independent methods categorizing the vaginal microbiome in at least three different CSTs to assess the risk of preterm birth were included. A (network) meta-analysis was conducted, presenting pooled odds ratios (OR) and 95% confidence intervals (CI); and weighted proportions and 95% CI. All 17 studies were published between 2014 and 2021 and included 38-539 pregnancies and 8-107 preterm births. Women presenting with "low-lactobacilli" vaginal microbiome were at increased risk (OR 1.69, 95% CI 1.15-2.49) for delivering preterm compared to Lactobacillus crispatus dominant women. Our network meta-analysis supports the microbiome being predictive of preterm birth, where low abundance of lactobacilli is associated with the highest risk, and L. crispatus dominance the lowest.
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Adverse pregnancy and birth outcomes associated with Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum: a systematic review and meta-analysis.
Jonduo, ME, Vallely, LM, Wand, H, Sweeney, EL, Egli-Gany, D, Kaldor, J, Vallely, AJ, Low, N
BMJ open. 2022;12(8):e062990
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Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum, referred to together as genital mycoplasmas, commonly colonise the urogenital tract in women, and are often found together. These species do not appear to cause symptoms or harmful effects in non-pregnant women. However, studies have reported that colonisation with a genital mycoplasma has been associated with several adverse pregnancy outcomes. The main objective of this study was to investigate the associations between M. hominis, U. urealyticum and/or U. parvum and the risk of pre-term birth, alone and in combination with bacterial vaginosis (BV). This study is a systematic review and meta-analysis of fifty-seven studies. Results show that genital mycoplasmas are associated with several different adverse pregnancy outcomes in univariable analysis only. Authors conclude that since only six of the fifty-seven studies reported multivariable analysis, the current available literature does not allow conclusions about the role of mycoplasmas in adverse pregnancy and birth outcomes, alone or with coexisting BV.
Abstract
OBJECTIVES Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum (genital mycoplasmas) commonly colonise the urogenital tract in pregnant women. This systematic review aims to investigate their role in adverse pregnancy and birth outcomes, alone or in combination with bacterial vaginosis (BV). METHODS We searched Embase, Medline and CINAHL databases from January 1971 to February 2021. Eligible studies tested for any of the three genital mycoplasmas during pregnancy and reported on the primary outcome, preterm birth (PTB) and/or secondary outcomes low birth weight (LBW), premature rupture of membranes (PROM), spontaneous abortion (SA) and/or perinatal or neonatal death (PND).Two reviewers independently screened titles and abstracts, read potentially eligible full texts and extracted data. Two reviewers independently assessed risks of bias using published checklists. Random effects meta-analysis was used to estimate summary ORs (with 95% CIs and prediction intervals). Multivariable and stratified analyses were synthesised descriptively. RESULTS Of 57/1194 included studies, 39 were from high-income countries. In meta-analysis of unadjusted ORs, M. hominis was associated with PTB (OR 1.87, 95% CI 1.49 to 2.34), PROM, LBW and PND but not SA. U. urealyticum was associated with PTB (OR 1.84, 95% CI 1.34 to 2.55), PROM, LBW, SA and PND. U. parvum was associated with PTB (1.60, 95% CI 1.12 to 2.30), PROM and SA. Nine of 57 studies reported any multivariable analysis. In two studies, analyses stratified by BV status showed that M. hominis and U. parvum were more strongly associated with PTB in the presence than in the absence of BV. The most frequent source of bias was a failure to control for confounding. CONCLUSIONS The currently available literature does not allow conclusions about the role of mycoplasmas in adverse pregnancy and birth outcomes, alone or with coexisting BV. Future studies that consider genital mycoplasmas in the context of the vaginal microbiome are needed. PROSPERO REGISTRATION NUMBER CRD42016050962.
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The Effect of Exogenous Sex Steroids on the Vaginal Microbiota: A Systematic Review.
Ratten, LK, Plummer, EL, Bradshaw, CS, Fairley, CK, Murray, GL, Garland, SM, Bateson, D, Tachedjian, G, Masson, L, Vodstrcil, LA
Frontiers in cellular and infection microbiology. 2021;11:732423
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A vaginal microbiota associated with optimal reproductive and sexual health outcomes is characterised by Lactobacillus spp., although microbiome composition varies across geographical locations and specific populations. The aim of this study was to summarise the effect of specific oestrogen-containing or progestin-only contraceptives as well as menopausal hormonal therapy (MHT) on the vaginal microbiota, and evaluate the strength of these findings. This study is a systematic review of twenty-nine studies out of which 25 studies reported on the effect of hormonal contraception among reproductive-aged women and four on the effect of MHT among post-menopausal women. This review shows that: - oestrogen-containing contraceptives, particularly the combined oestrogen and progestin-containing oral contraceptive pill, had a positive effect on the composition of the vaginal microbiota. - among post-menopausal women using MHT, exogenous oestrogen also appeared to positively influence the vaginal microbiota. - exogenous-oestrogen as an adjunctive therapy does not impact the composition of the vaginal microbiota in a detrimental way. - the impact of progestin-only hormonal contraceptives was less consistent as there was equal evidence that they have either a negative or neutral impact on the vaginal microbiota. Authors conclude that their findings confirm the potential benefits of exogenous oestrogen in conferring a vaginal microbiota associated with optimal health outcomes for women.
Abstract
BACKGROUND Exogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms, without consideration of their effects on the vaginal microbiota. This is largely because their use predates our understanding of the importance of the vaginal microbiome on human health. We conducted a systematic review (PROSPERO CRD42018107730) to determine the influence of exogenous sex steroids, stratified by oestrogen-containing or progestin-only types of contraception, and MHT on the vaginal microbiome, as measured by molecular methods. METHODS Embase, PubMed and Medline were searched for relevant literature published through to December 1st 2020. Eligible studies reported on the effect of specific exogenous sex steroids on the vaginal microbiome using a molecular method. Data regarding the 'positive', 'negative' or 'neutral' effect of each type of contraceptive or MHT on the vaginal microbiome was extracted and summarised. A positive effect reflected sex steroid exposure that was associated with increased abundance of lactobacilli, a change to, or maintenance of, an optimal vaginal microbiota composition, or a decrease in bacterial diversity (specifically reflecting a low-diversity optimal microbiota state), relative to the control group. An exogenous sex steroid was designated as having a negative effect on the vaginal microbiome if it resulted in opposing effects (i.e. loss of lactobacilli, a non-optimal microbiota state). When no significant change was found, this was considered neutral/inconclusive. RESULTS We identified 29 manuscripts reporting on the effect of exogenous sex steroids on the vaginal microbiome; 25 investigating hormonal contraceptives, and 4 investigating MHT. Oestrogen-containing contraception, particularly reflecting the combined oestrogen and progestin-containing contraceptive pill, had a positive effect on the composition of the vaginal microbiota. Progestin-only contraception, particularly reflecting depo-medroxyprogesterone acetate, had mixed effects on the microbiota. Among post-menopausal women using MHT, exogenous oestrogen applied topically was associated with increased prevalence of lactobacilli. CONCLUSION Our findings suggest that oestrogen-containing compounds may promote an optimal vaginal microbiota, which could have clinical applications. The impact of progestin-only contraceptives on the vaginal microbiota is less clear; more data is needed to determine how progestin-only contraceptives contribute to adverse reproductive and sexual health outcomes.
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Association between plant-based diets and plasma lipids: a systematic review and meta-analysis.
Yokoyama, Y, Levin, SM, Barnard, ND
Nutrition reviews. 2017;75(9):683-698
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Plasma lipids play a prominent role in heart disease and modifiable factors such as diet and lifestyle can facilitate in preventing or developing hyperlipidemia. Previous research has suggested that vegetarian diets are associated with lower plasma lipid concentrations, however long-term impacts of consuming a plant-based diet (PBD) has not been studied. The aim of this research was to conduct a systematic review and meta-analysis for studies that have examined the relationship between PBDs and plasma lipids. Thirty observational studies and 19 clinical trials were included in this analysis and showed consumption of a PBD was significantly associated with lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), but not in triglyceride concentrations. Based on these results, the authors conclude PBDs could offer individuals and healthcare professionals an effective option for reducing heart disease. They also add that while dietary changes may not be as powerful as pharmaceutical drugs in reducing plasma lipids, dietary and pharmacologic interventions can work together.
Abstract
CONTEXT Although a recent meta-analysis of randomized controlled trials showed that adoption of a vegetarian diet reduces plasma lipids, the association between vegetarian diets and long-term effects on plasma lipids has not been subjected to meta-analysis. OBJECTIVE The aim was to conduct a systematic review and meta-analysis of observational studies and clinical trials that have examined associations between plant-based diets and plasma lipids. DATA SOURCES MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for articles published in English until June 2015. STUDY SELECTION The literature was searched for controlled trials and observational studies that investigated the effects of at least 4 weeks of a vegetarian diet on plasma lipids. DATA EXTRACTION Two reviewers independently extracted the study methodology and sample size, the baseline characteristics of the study population, and the concentrations and variance measures of plasma lipids. Mean differences in concentrations of plasma lipids between vegetarian and comparison diet groups were calculated. Data were pooled using a random-effects model. RESULTS Of the 8385 studies identified, 30 observational studies and 19 clinical trials met the inclusion criteria (N = 1484; mean age, 48.6 years). Consumption of vegetarian diets was associated with lower mean concentrations of total cholesterol (-29.2 and -12.5 mg/dL, P < 0.001), low-density lipoprotein cholesterol (-22.9 and -12.2 mg/dL, P < 0.001), and high-density lipoprotein cholesterol (-3.6 and -3.4 mg/dL, P < 0.001), compared with consumption of omnivorous diets in observational studies and clinical trials, respectively. Triglyceride differences were -6.5 (P = 0.092) in observational studies and 5.8 mg/dL (P = 0.090) in intervention trials. CONCLUSIONS Plant-based diets are associated with decreased total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but not with decreased triglycerides. SYSTEMATIC REVIEW REGISTRATION PROSPERO number CRD42015023783. Available at: https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015023783.
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Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis.
Bailie, L, Loughrey, MB, Coleman, HG
Gastroenterology. 2017;152(1):92-104
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Colorectal cancer (CRC) is a heterogeneous disease thought to result from the accumulation of various aberrant mutations in the cells lining the colorectal mucosa. The aim of this systematic review and meta-analysis was to evaluate modifiable and lifestyle factors and the risk of serrated polyps (a type of growth that stick out from the surface of the colon or rectum) of the colorectum. A search of 3 databases yielded a potential 2446 studies for inclusion, from which 43 remained for systematic review. Results indicate that smoking, alcohol consumption, body fatness, dietary fat and meat consumption increased the risk of developing serrated polyps. Whereas, nonsteroidal anti-inflammatory drugs, aspirin and dietary folate decreased this risk. Authors conclude that their findings strengthen public health messages promoting awareness and change in order to reduce the risk of these precancerous lesions and consequently CRC.
Abstract
BACKGROUND & AIMS Certain subsets of colorectal serrated polyps (SP) have malignant potential. We performed a systematic review and meta-analysis to investigate the association between modifiable lifestyle factors and risk for SPs. METHODS We conducted a systematic search of Medline, Embase, and Web of Science for observational or interventional studies that contained the terms risk or risk factor, and serrated or hyperplastic, and polyps or adenomas, and colorectal (or synonymous terms), published by March 2016. Titles and abstracts of identified articles were independently reviewed by at least 2 reviewers. Adjusted relative risk (RR) and 95% confidence interval (CI) were combined using random effects meta-analyses to assess the risk of SP, when possible. RESULTS We identified 43 studies of SP risk associated with 7 different lifestyle factors: smoking, alcohol, body fatness, diet, physical activity, medication, and hormone-replacement therapy. When we compared the highest and lowest categories of exposure, factors we found to significantly increase risk for SP included tobacco smoking (RR, 2.47; 95% CI, 2.12-2.87), alcohol intake (RR, 1.33; 95% CI, 1.17-1.52), body mass index (RR, 1.40; 95% CI, 1.22-1.61), and high intake of fat or meat. Direct associations for smoking and alcohol, but not body fat, tended to be stronger for sessile serrated adenomas/polyps than hyperplastic polyps. In contrast, factors we found to significantly decrease risks for SP included use of nonsteroidal anti-inflammatory drugs (RR, 0.77; 95% CI, 0.65-0.92) or aspirin (RR, 0.81; 95% CI, 0.67-0.99), as well as high intake of folate, calcium, or fiber. No significant associations were detected between SP risk and physical activity or hormone replacement therapy. CONCLUSIONS Several lifestyle factors, most notably smoking and alcohol, are associated with SP risk. These findings enhance our understanding of mechanisms of SP development and indicate that risk of serrated pathway colorectal neoplasms could be reduced with lifestyle changes.