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Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review.
Alkurd, R, Mahrous, L, Zeb, F, Khan, MA, Alhaj, H, Khraiwesh, HM, Faris, ME
Medicina (Kaunas, Lithuania). 2024;60(1)
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Brain-derived neurotrophic factor (BDNF) is a protein that plays a crucial role in brain development, cognition and metabolism. Intermittent fasting (IF) is a promising therapeutic strategy for managing metabolic disorders and improving cognitive function. Therefore, this systematic review of sixteen experimental and observational studies investigated the effect of IF on BDNF production and improvements in cognition through the BDNF pathway in healthy adults and people with metabolic disorders. Included studies focused on different IF regimens such as calorie restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE) and Ramadan model of intermittent fasting (RIF) Future, well-controlled, long-term, robust studies are required to assess the effect of different IF regimens on the production of BDNF and cognitive function in people with metabolic disorders, as the current research is inconclusive. However, healthcare professionals can use the review to understand the potential beneficial effects of IF on cognition and metabolic health in humans.
Abstract
Background: The potential positive interaction between intermittent fasting (IF) and brain-derived neurotrophic factor (BDNF) on cognitive function has been widely discussed. This systematic review tried to assess the efficacy of interventions with different IF regimens on BDNF levels and their association with cognitive functions in humans. Interventions with different forms of IF such as caloric restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE), and the Ramadan model of intermittent fasting (RIF) were targeted. Methods: A systematic review was conducted for experimental and observational studies on healthy people and patients with diseases published in EMBASE, Scopus, PubMed, and Google Scholar databases from January 2000 to December 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statements (PRISMA) for writing this review. Results: Sixteen research works conducted on healthy people and patients with metabolic disorders met the inclusion criteria for this systematic review. Five studies showed a significant increase in BDNF after the intervention, while five studies reported a significant decrease in BDNF levels, and the other six studies showed no significant changes in BDNF levels due to IF regimens. Moreover, five studies examined the RIF protocol, of which, three studies showed a significant reduction, while two showed a significant increase in BDNF levels, along with an improvement in cognitive function after RIF. Conclusions: The current findings suggest that IF has varying effects on BDNF levels and cognitive functions in healthy, overweight/obese individuals and patients with metabolic conditions. However, few human studies have shown that IF increases BDNF levels, with controversial results. In humans, IF has yet to be fully investigated in terms of its long-term effect on BDNF and cognitive functions. Large-scale, well-controlled studies with high-quality data are warranted to elucidate the impact of the IF regimens on BDNF levels and cognitive functions.
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Outcome-Specific Efficacy of Different Probiotic Strains and Mixtures in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.
Xie, P, Luo, M, Deng, X, Fan, J, Xiong, L
Nutrients. 2023;15(17)
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Irritable bowel syndrome (IBS) is a common functional bowel disease that is induced by disorders of gut–brain interactions. Typical symptoms of IBS include recurrent abdominal pain associated with changes in stool form or frequency. The aim of this study was to evaluate the comparative efficacy of different probiotic strains and mixtures based on global conditions, mental health levels, and specific gastrointestinal symptoms. This study was a systematic review and network meta-analysis (NMA) of eighty-one randomised controlled trials. Results showed that only some probiotic strains and combinations were more effective than the placebo for each specific outcome of IBS. Authors concluded that probiotics should be selected according to the specific symptoms of IBS patients.
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disease. The efficacy of different probiotics in treating IBS remains controversial. This network meta-analysis aimed to compare and rank the outcome-specific efficacy of different probiotic strains or combinations in adults with IBS. We searched the literature up to June 2023. Randomized controlled trials (RCTs) that evaluated the efficacy of probiotics in IBS were included. A frequentist framework was used to perform this study. In total, 9253 participants from 81 RCTs were included in the study. Four probiotic strains and five mixtures were significantly superior to placebo in improving IBS Symptom Severity Scale, among which Lactobacillus acidophilus DDS-1 ranked first (surface under the cumulative ranking, SUCRA, 92.9%). A mixture containing five probiotics (SUCRA, 100%) ranked first in improving the IBS-Quality of life. Bacillus coagulans MTCC 5856 (SUCRA, 96.9%) and Bacillus coagulans Unique IS2 (SUCRA, 92.6%) were among the most effective probiotics for improving abdominal pain. Three probiotic strains and two mixtures were effective in alleviating abdominal bloating. Four probiotic strains and a mixture were significantly superior to placebo in reducing the bowel movement frequency in diarrhea-predominant IBS (IBS-D). Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D. Only some probiotics are effective for particular outcomes in IBS patients. This study provided the first ranking of outcome-specific efficacy of different probiotic strains and combinations in IBS. Further studies are needed to confirm these results.
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Examining the Association between Coffee Intake and the Risk of Developing Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.
Lee, JY, Yau, CY, Loh, CYL, Lim, WS, Teoh, SE, Yau, CE, Ong, C, Thumboo, J, Namasivayam, VSO, Ng, QX
Nutrients. 2023;15(22)
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Irritable bowel syndrome (IBS) is a highly prevalent disorder of brain–gut interaction with a significant impact on quality of life and social functioning. Diet has been implicated in the pathophysiology of IBS as well as disease flares. A significant proportion of IBS patients experience food-related symptoms associated with consuming or eliminating certain foods. This study's aim was to determine if there is an association between coffee intake and the likelihood of developing IBS. This study was a systematic review and meta-analysis of eight studies with 432,022 participants. Results showed that coffee drinkers (any intake) may have a decreased risk of developing IBS compared to controls. However, these findings must be interpreted in light of several shortcomings. Authors concluded that future studies should (1) prioritise high-quality prospective cohort studies with well-documented coffee consumption (and exposure) and track the development of incident IBS in previously healthy individuals over time, and (2) investigate biological mechanisms.
Abstract
Irritable bowel syndrome (IBS) is a highly prevalent disorder of brain-gut interaction with a significant impact on quality of life. Coffee is a widely consumed beverage with numerous bioactive compounds that have potential effects on human health and disease states. Current studies on the effect of regular coffee consumption on the risk of developing IBS symptoms have yielded conflicting results. This systematic review and meta-analysis aimed to determine whether coffee intake is associated with developing IBS. A systematic literature search was performed in three electronic databases, namely PubMed, EMBASE, and The Cochrane Library, from inception until 31 March 2023. All original studies reporting associations between coffee intake and IBS were considered for inclusion. Odds ratios (ORs) were calculated for each study, and estimates were pooled, and where appropriate, 95% confidence intervals (95% CI) and p-values were calculated. Eight studies comprising 432,022 patients were included in the final meta-analysis. Using a fixed-effects model, coffee drinkers (any intake) had a reduced likelihood of developing IBS compared to controls, with a pooled OR of 0.84 (95% CI: 0.80 to 0.84). Sensitivity analysis confirmed the stability of the estimates. Future research should prioritise prospective cohort studies that are robust and closely track the development of incident IBS in previously healthy individuals.
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Do Colonic Mucosal Tumor Necrosis Factor Alpha Levels Play a Role in Diverticular Disease? A Systematic Review and Meta-Analysis.
Sabo, CM, Ismaiel, M, Ismaiel, A, Leucuta, DC, Popa, SL, Grad, S, Dumitrascu, DL
International journal of molecular sciences. 2023;24(12)
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Diverticular disease (DD) is a disease of the colon that can be split into symptomatic uncomplicated diverticular disease (SUDD), asymptomatic complicated, and segmental colitis associated with diverticulosis (SCAD). They are all diseases of the colon that are poorly understood. It is thought that inflammation of the colon may play a part in their development, however levels of certain inflammatory biomarkers have shown contradicting relationships. This systematic review of 12 studies and meta-analysis of 6 of these aimed to determine the role of one inflammatory biomarker known as tumour necrosis factor-alpha (TNF-a) in DD. The results showed that mucosal TNF-a levels were unchanged in individuals with SUDD compared to healthy controls. They were also unchanged in SUDD vs asymptomatic DD. They were higher in individuals with DD and SCAD when compared to individuals with irritable bowel syndrome (IBS). It was concluded that TNF-a may be involved in the development of specific types of DD. This study could be used by healthcare professionals to understand that the management of inflammation in individuals with DD may be of benefit.
Abstract
Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI -1.148-2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI -0.883-2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744-30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823-30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies.
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Effects of Probiotics on Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis of Clinical Trials.
He, X, Liu, W, Tang, F, Chen, X, Song, G
Nutrients. 2023;15(6)
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Autism spectrum disorder (ASD) is a developmental disability caused by differences in the brain and is characterized by a series of neurodevelopmental disorders, including language and social disorders, restricted interests, and repetitive stereotyped activities. The aim of this study was to explore whether probiotics could improve the overall severity of ASD symptoms in children. This study was a systematic review and meta-analysis of seven studies. Results showed that probiotic supplementation did not improve the associated behavioural symptoms in children with ASD. However, multiple-strain probiotic blend intervention exhibited a positive therapeutic effect on children with ASD and was more effective than single-strain probiotics in subgroup analyses. Authors concluded that to demonstrate the therapeutic effects of probiotics on children with ASD, randomised, double-blind, and placebo-controlled studies following strict trial guidelines are needed.
Abstract
Many studies have explored the efficacy of probiotics on autism spectrum disorder (ASD) in children, but there is no consensus on the curative effect. This systematic review and meta-analysis aimed to comprehensively investigate whether probiotics could improve behavioral symptoms in children with ASD. A systematic database search was conducted and a total of seven studies were included in the meta-analysis. We found a nonsignificant overall effect size of probiotics on behavioral symptoms in children with ASD (SMD = -0.24, 95% CI: -0.60 to 0.11, p = 0.18). However, a significant overall effect size was found in the subgroup of the probiotic blend (SMD = -0.42, 95% CI: -0.83 to -0.02, p = 0.04). Additionally, these studies provided limited evidence for the efficacy of probiotics due to their small sample sizes, a shorter intervention duration, different probiotics used, different scales used, and poor research quality. Thus, randomized, double-blind, and placebo-controlled studies following strict trial guidelines are needed to precisely demonstrate the therapeutic effects of probiotics on ASD in children.
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The Effects of Probiotics/Synbiotics on Glucose and Lipid Metabolism in Women with Gestational Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.
Mu, J, Guo, X, Zhou, Y, Cao, G
Nutrients. 2023;15(6)
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Women with gestational diabetes mellitus (GDM) are at an increased risk of complications during pregnancy and type 2 diabetes, pancreatic cancer, and heart disease after pregnancy. There is some controversy over the research surrounding current treatments of GDM and as such new treatment strategies are being researched and developed. Amongst these is the possibility of using probiotics and synbiotics to alleviate the driving factors of GDM, however the research is inconclusive as some studies have shown a benefit whereas others have not. This meta-analysis of 11 randomised control trials (RCTs) containing 779 participants aimed to determine the effect of probiotic/synbiotics on sugar and lipid levels in the blood. The results showed that amongst 8 of the RCTs, Lactobacillus was the most researched probiotic gut bacteria, with 6 species researched. In addition, Bifidobacterium bifidum and Streptococcus thermophilus were also used as a probiotic. 3 RCTs looked at synbiotics including 5 Lactobacillus species and 3 Bifidobacterium species. Supplementation with probiotics/synbiotics significantly improved blood sugar levels, measures of insulin resistance, and total cholesterol in pregnant women with GDM. Other blood lipids such as triglycerides, high density lipoprotein, low density lipoprotein, weight at the end of the trial, and weight gain during pregnancy were unaffected by supplementation. It was concluded that probiotics/synbiotics are of benefit to women with GDM especially if they contain L. acidophilus and B. bifidum. However, there may be more research required to better inform GDM management. This study could be used by healthcare professionals to understand that the gut microbiota may have a pivotal role in GDM. More research is required before this forms part of a regular management strategy.
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is prevalent with lasting health implications for the mother and offspring. Medical therapy is the foundation of GDM management, for achieving optimal glycemic control often requires treatment with insulin or metformin. Gut dysbiosis is a feature of GDM pregnancies, therefore, dietary manipulation of the gut microbiota may offer a new avenue for management. Probiotics are a relatively new intervention, which can reduce the mother's blood sugar levels and, furthermore, adjust glucose and lipid metabolism in both mother and offspring. OBJECTIVE The aim of this systematic review and meta-analysis is to explore the effect of probiotics/synbiotics on glucose and lipid metabolism in women with GDM. METHODS A systematic search of the literature was conducted using the electronic databases Cochrane Library, Web of Science, PubMed, and EBOSCO, published between 1 January 2012 and 1 November 2022. A total of 11 randomized controlled clinical trials (RCTs) were analyzed. The indicators included fasting plasma glucose (FPG), fasting serum insulin (FSI), the homoeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides (TG), the mean weight at end of trial, and gestational weight gain (GWG). RESULTS Compared with the placebo, probiotics/synbiotics were associated with a statistically significant improvement in FPG (MD = -2.33, 95% CI = -4.27, -0.40, p = 0.02), FSI (MD = -2.47 95% CI = -3.82, -1.12, p = 0.0003), HOMA-IR (MD = -0.40, 95% CI = -0.74, -0.06, p = 0.02), and TC (MD = -6.59, 95% CI = -12.23,--0.95, p = 0.02), while other factors had no significant difference. The subgroup analysis revealed that the kind of supplement led to heterogeneity for FPG and FSI, while heterogeneity was not found for others. CONCLUSION Probiotics/synbiotics could control glucose and lipid metabolism in pregnant women with GDM. There was a significant improvement in FPG, FSI, HOMA-IR, and TC. The use of specific probiotic supplementation may be a promising prevention and therapeutic strategy for GDM. However, due to the heterogeneity among existing studies, further studies are warranted to address the limitations of existing evidence and better inform the management of GDM.
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The effects of probiotics supplementation on glycaemic control among adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomised clinical trials.
Li, G, Feng, H, Mao, XL, Deng, YJ, Wang, XB, Zhang, Q, Guo, Y, Xiao, SM
Journal of translational medicine. 2023;21(1):442
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Type 2 diabetes mellitus (T2DM), an endocrine and metabolic disease, is influenced by host physiology and environmental factors. Recent studies have shown that the gut microbiota plays a key role in the maintenance of host homeostasis and pathogenesis of T2DM. The aim of this study was to evaluate the effects of a probiotic intervention on glycaemic control in T2DM patients and to evaluate the variations in these effects due to participant characteristics and intervention characteristics. This study was a systematic review and meta-analysis of thirty randomised-controlled studies including a total of 1,827 individuals. Results showed that probiotic supplementation had favourable effects on glycaemic control in T2DM patients. Bifdobacterium and food-type probiotics had greater glucose-lowering effects than other probiotic genera and types of vehicles used to deliver the probiotics. Authors concluded that the administration of probiotics may be a promising adjuvant therapy for glycaemic control in T2DM patients.
Abstract
OBJECTIVE This systematic review and meta-analysis study aimed to evaluate the effectiveness of probiotics supplementation on glycaemic control in patients with type 2 diabetes mellitus (T2DM) based on the data from the randomised clinical trials (RCTs). METHODS PubMed, Web of Sciences, Embase, and Cochrane Library were searched from the inception to October 2022, and RCTs about probiotics and T2DM were collected. The standardised mean difference (SMD) with 95% confidence interval (CI) was used to estimate the effects of probiotics supplementation on glycaemic control related parameters, e.g. fasting blood glucose (FBG), insulin, haemoglobin A1c (HbA1c), and homeostasis model of assessment of insulin resistance (HOMA-IR). RESULTS Thirty RCTs including 1,827 T2MD patients were identified. Compared with the placebo group, the probiotics supplementation group had a significant decrease in the parameters of glycaemic control, including FBG (SMD = - 0.331, 95% CI - 0.424 to - 0.238, Peffect < 0.001), insulin (SMD = - 0.185, 95% CI - 0.313 to - 0.056, Peffect = 0.005), HbA1c (SMD = - 0.421, 95% CI - 0.584 to - 0.258, Peffect < 0.001), and HOMA-IR (SMD = - 0.224, 95% CI - 0.342 to - 0.105, Peffect < 0.001). Further subgroup analyses showed that the effect was larger in the subgroups of Caucasians, high baseline body mass index (BMI ≥ 30.0 kg/m2), Bifidobacterium and food-type probiotics (Psubgroup < 0.050). CONCLUSION This study supported that probiotics supplementation had favourable effects on glycaemic control in T2DM patients. It may be a promising adjuvant therapy for patients with T2DM.
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Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis.
Prokopidis, K, Mazidi, M, Sankaranarayanan, R, Tajik, B, McArdle, A, Isanejad, M
The British journal of nutrition. 2023;129(5):759-770
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Reduced muscle mass and reduction in physical activity may lead to sarcopenia in older people. Age-related sarcopenia is associated with increased systemic low-grade inflammation and obesity. Protein supplementation is found to be beneficial in reducing circulating pro-inflammatory cytokines in old people. Previous research has shown that supplementation with isolated whey and soy protein reduces the levels of inflammatory cytokines in older adults. However, there is limited research on intact whey and soy protein supplementation in reducing age-related inflammation. This systematic review and meta-analysis investigated the effect of intact whey and soy protein on serum inflammatory markers such as C-reactive protein (CRP), Interleukin-6 (IL6) and TNF-α in older adults. The results of this meta-analysis show a significant reduction in circulating IL-6 and TNF-α levels after the supplementation with whey and soy protein. The addition of soy isoflavones resulted in a further decline in serum CRP levels. Subgroup analysis showed that the whey protein supplementation significantly improved sarcopenia and pre-frailty. Healthcare professionals can use the result of this systematic review and meta-analysis to understand the anti-inflammatory properties of intact whey and soy protein and soy isoflavones. However, further robust studies are required to assess the anti-inflammatory properties of whey and soy protein due to the high heterogeneity of included studies in this review.
Abstract
BACKGROUND AND AIMS Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers. METHODS We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603). RESULTS Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): -0·79, 95 % CI: -1·15, -0·42, I2 = 96 %] and TNF-α levels following soy protein supplementation (MD: -0·16, 95 % CI: -0·26, -0·05, I2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: -0·20, 95 % CI: -0·31, -0·08, I2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: -0·98, 95 % CI: -1·56, -0·39, I2 = 0 %). These findings may be dependent on participant characteristics and treatment duration. CONCLUSIONS These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.
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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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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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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.