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Efficacy of probiotics or synbiotics in critically ill patients: A systematic review and meta-analysis.
Lou, J, Cui, S, Huang, N, Jin, G, Chen, C, Fan, Y, Zhang, C, Li, J
Clinical nutrition ESPEN. 2024;59:48-62
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The intestinal microbiota is a complex microbial community that plays an irreplaceable role in human life. Intestinal dysbiosis is very common in patients with critical illnesses. The aim of this study was to assess the efficacy and safety of probiotics or synbiotics in preventing ventilator associated pneumonia (VAP) in critically ill patients in the intensive care unit (ICU). This study was a systematic review and meta-analysis of thirty-three trials (n=4 retrospective studies and n=29 randomised controlled studies). A total of 7886 patients were grouped into the probiotics or synbiotics group (n= 4065) and control group (n= 3821). Results showed that probiotics or synbiotics significantly reduced the incidence of VAP and sepsis, as well as the duration of mechanical support, length of hospital stay, length of ICU stay, and ICU morality. Authors concluded that probiotics or synbiotics supplementation plays a beneficial role in critically ill patients and presents a novel approach to the management of critical diseases.
Abstract
BACKGROUND This latest systematic review and meta-analysis aim to examine the effects of probiotic and synbiotic supplementation in critically ill patients. METHODS Relevant articles were retrieved from PubMed, Embase, the Cochrane Database, and the Web of Science. The primary output measure was the incident of ventilator-associated pneumonia, and the secondary outputs were diarrhea, Clostridium diffusion infection (CDI), incident of sepsis, incident of hospital acquired pneumonia, duration of mechanical exploitation, ICU mortality rate, length of ICU stay, in hospital mortality, and length of hospital stay. Data were pooled and expressed as Relative Risk(RR) and Standardized Mean Difference (SMD) with a 95 % confidence interval (CI). RESULTS 33 studies were included in this systematic review and meta-analysis, with 4065 patients who received probiotics or synbiotics (treatment group) and 3821 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced incidence of ventilation-associated pneumonia (VAP) (RR = 0.80; 95 % CI: 0.67-0.96; p = 0.021, I2 = 52.5 %) and sepsis (RR = 0.97; 95 % CI: 0.66-1.42; p = 0.032, I2 = 54.4 %), As well as significantly increased duration of mechanical exploitation (SMD = -0.47; 95 % CI: -0.74-0.20, p = 0.012, I2 = 63.4 %), ICU mobility (RR = 0.95; 95 % CI: 0.71-1.27; p = 0.004, I2 = 62.8 %), length of ICU stay (SMD = -0.29; 95 % CI: -0.58-0.01; p = 0.000, I2 = 82.3 %) and length of hospital stay (SMD = -0.33; 95 % CI: -0.57-0.08, p = 0.000, I2 = 74.2 %) than the control group. There were no significant differences in diarrhea, CDI, incidence of hospital acquired pneumonia, and in hospital mortality between the two groups. CONCLUSION Our meta-analysis showed that probiotic and synbiotic supplements are beneficial for critically ill patients as they significantly reduce the incidence of ventilator associated pneumonia and sepsis, as well as the duration of mechanical exploitation, length of hospital stay, length of ICU stay, and ICU mortality. However, this intervention has minimal impact on diarrhea, CDI, incidence of hospital acquired pneumonia, and in hospital mortality in critically ill patients.
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Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial.
Ni Lochlainn, M, Bowyer, RCE, Moll, JM, García, MP, Wadge, S, Baleanu, AF, Nessa, A, Sheedy, A, Akdag, G, Hart, D, et al
Nature communications. 2024;15(1):1859
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Humans lose skeletal muscle with advancing age, and this can progress to sarcopenia. Dietary protein is crucial for maintaining skeletal muscle health; however, several factors can lead to reduced protein intake in older age. The aim of this study was to test whether the addition of gut microbiome modulation could augment established muscle function improvements from combined protein (branched chain amino acids [BCAA]) and resistance exercise. This study was based on the PROMOTe (effect of PRebiotic and prOtein on Muscle in Older Twins) trial which was a randomised controlled trial in which twin pairs (n= 72) were randomised, one twin to each study arm. Results showed that prebiotics improved cognition but did not impact muscle strength and function, compared with placebo. Furthermore, gut microbiome modulation via prebiotic supplementation in the context of ageing-muscle research is feasible and well tolerated, with clear responses noted in the gut microbiota composition and function. Authors concluded that cheap and readily available gut microbiome interventions hold promise for improving cognitive frailty in our ageing population.
Abstract
Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.
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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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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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Effect of prebiotics, probiotics, synbiotics on depression: results from a meta-analysis.
Zhang, Q, Chen, B, Zhang, J, Dong, J, Ma, J, Zhang, Y, Jin, K, Lu, J
BMC psychiatry. 2023;23(1):477
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Major depressive disorder (MDD) is a mood disorder that impairs psychosocial function and quality of life. Recent studies show that prebiotics, probiotics, and synbiotics reveal a novel way to treat psychiatric disorders such as depression through the microbiota-gut-brain axis. The aim of this study was to evaluate the effectiveness of prebiotics, probiotics and synbiotics in alleviating depressive symptoms. This study was a meta-analysis of thirteen studies with a total of 786 participants who were allocated to the intervention group (n=427) and the placebo group (n=359). Results showed that the overall effects of probiotics, prebiotics and synbiotics on depressive symptoms were significantly superior to those of placebo. Additionally, biological sex was a vital factor that influenced patients’ responses to the treatment. Authors concluded that agents that manipulate gut microbiota might become a novel approach to treat patients with mild-to-moderate depression.
Abstract
Accumulating studies have shown the effects of gut microbiota management tools in improving depression. We conducted a meta-analysis to evaluate the effects of prebiotics, probiotics, and synbiotics on patients with depression. We searched six databases up to July 2022. In total, 13 randomized controlled trials (RCTs) with 786 participants were included. The overall results demonstrated that patients who received prebiotics, probiotics or synbiotics had significantly improved symptoms of depression compared with those in the placebo group. However, subgroup analysis only confirmed the significant antidepressant effects of agents that contained probiotics. In addition, patients with mild or moderate depression could both benefit from the treatment. Studies with a lower proportion of females reported stronger effects for alleviating depressive symptoms. In conclusion, agents that manipulate gut microbiota might improve mild-to-moderate depression. It is necessary to further investigate the benefits of prebiotic, probiotic and synbiotic treatments relative to antidepressants and follow up with individuals over a longer time before these therapies are implemented in clinical practice.
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Probiotics and non-alcoholic fatty liver disease in children and adolescents: a systematic review.
Avelar-Rodríguez, D, Peña-Vélez, R, Popov, J, Hill, L, Ryan, PM
Revista espanola de enfermedades digestivas. 2023;115(8):418-427
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Non-alcoholic fatty liver disease (NAFLD), as a direct result of the escalating childhood obesity epidemic, is a significant public health issue globally. NAFLD is the most common cause of chronic liver disease in the paediatric population. The aim of this study was to assess the quality of evidence currently available for the use of microbial therapies (i.e., prebiotics, probiotics, and synbiotics) in the treatment of NAFLD in children with obesity. This study was a systematic review and meta-analysis of five randomised controlled studies. Results showed that although there is a range of promising effects on both clinical and biochemical parameters, significant interstudy discrepancies reduce reliability and generalisability of these results. Authors concluded there is insufficient evidence to support the beneficial role of probiotics and synbiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials.
Abstract
BACKGROUND non-alcoholic fatty liver disease (NAFLD) in childhood is an increasing global public health issue with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesize all the available literature on the use of probiotics in children and adolescents with NAFLD. METHODS PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library were systematically searched for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD. RESULTS five randomized controlled trials met the inclusion criteria. Of these, four trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of alanine aminotransferase (ALT) (mean difference: -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93 %). CONCLUSIONS there is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children.
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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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Effects of probiotic administration on overweight or obese children: a meta-analysis and systematic review.
Li, Y, Liu, T, Qin, L, Wu, L
Journal of translational medicine. 2023;21(1):525
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The prevalence of overweight or obesity in children is increasing due to changes in dietary structure and exercise habits, as determined by the body mass index (BMI) calculated from height and weight. Childhood obesity can cause some clinical complications such as hypertension, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease. The aim of this study was to examine the effects of probiotics on eight factors in children with overweight or obesity. This study was a systematic review and meta-analysis of four studies with a total of 206 overweight or obesity children. Among them, 105 were in the probiotic group, and 101 were in the placebo group. Results showed that probiotics can improve high- and low-density lipoprotein cholesterol, adiponectin, leptin, and TNF-α in overweight or obese children. The systematic review showed that probiotics work mainly by reshaping disturbed intestinal microbiota, regulating lipid metabolism, reducing inflammation and immune response, playing a positive effect of short-chain fatty acids produced, alleviating oxidative stress and endoplasmic reticulum stress, and inhibiting the growth and reproduction of pathogens in the gut. Authors concluded that probiotics could regulate lipid metabolism and immune response to some degree in children with overweight or obesity.
Abstract
BACKGROUND This paper aimed to examine the effects of probiotics on eight factors in overweight or obese children by meta-analysis, namely, body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), adiponectin, leptin and tumor necrosis factor-α (TNF-α) and summarize the mechanisms of action of probiotics based on the existing researches. METHODS Six databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed and CNKI) were searched until March 2023. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model or random effect model to observe the effects of probiotic administration on the included indicators. RESULTS Four publications with a total of 206 overweight or obesity children were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HDL-C (MD, 0.06; 95% CI 0.03, 0.09; P = 0.0001), LDL-C (MD, - 0.06; 95% CI - 0.12, - 0.00; P = 0.04), adiponectin (MD, 1.39; 95% CI 1.19, 1.59; P < 0.00001), leptin (MD, - 2.72; 95% CI - 2.9, - 2.54; P < 0.00001) and TNF-α (MD, - 4.91; 95% CI - 7.15, - 2.67; P < 0.0001) compared to those in the placebo group. Still, for BMI, the palcebo group seemed to be better than the probiotic group (MD, 0.85; 95% CI 0.04, 1.66; P = 0.04). TC (MD, - 0.05; 95% CI - 0.12, 0.02; P = 0.14) and TG (MD, - 0.16; 95% CI - 0.36, 0.05; P = 0.14) were not different between two groups. CONCLUSIONS This review drew that probiotics might act as a role in regulating HDL-C, LDL-C, adiponectin, leptin and TNF-α in overweight or obesity children. Additionally, our systematic review yielded that probiotics might regulate lipid metabolism and improve obese associated symptoms by some paths. This meta-analysis has been registered at PROSPERO with ID: CRD42023408359.
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Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis.
Akinsuyi, OS, Roesch, LFW
Microbiology spectrum. 2023;11(3):e0032223
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Osteoporosis (OP) is the most common metabolic bone disease associated with aging. Microbiome dysbiosis leading to impaired intestinal immune responses and subsequent production of osteoclastogenic cytokines has been proposed as the mechanism by which gut microbes are associated with osteoporosis. The aim of this study was to identify gut bacteria consistently associated with osteoporosis across different cohorts. This study was a meta-analysis of five studies. Results showed that gut microbial dysbiosis in osteoporosis patients is associated with functional changes, which result in significant changes in metabolites that play a key role in bone metabolism. Authors concluded that their findings set the stage for future studies to provide more comprehensive knowledge on how dysbiosis in the gut microbiome contributes to osteoporosis.
Abstract
Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational studies has linked changes in the gut microbiota to the pathophysiology of osteoporosis (OP). Nonetheless, the results of these studies contain discrepancies, leaving the literature without a consensus on osteoporosis-associated microbial signatures. Here, we conducted a comprehensive meta-analysis combining and reexamining five publicly available 16S rRNA partial sequence data sets to identify gut bacteria consistently associated with osteoporosis across different cohorts. After adjusting for the batch effect associated with technical variation and heterogeneity of studies, we observed a significant shift in the microbiota composition in the osteoporosis group. An increase in the relative abundance of opportunistic pathogens Clostridium sensu stricto, Bacteroides, and Intestinibacter was observed in the OP group. Moreover, short-chain-fatty-acid (SCFA) producers, including members of the genera Collinsella, Megasphaera, Agathobaculum, Mediterraneibacter, Clostridium XIV, and Dorea, were depleted in the OP group relative to the healthy control (HC) group. Lactic acid-producing bacteria, including Limosilactobacillus, were significantly increased in the OP group. The random forest algorithm further confirmed that these bacteria differentiate the two groups. Furthermore, functional prediction revealed depletion of the SCFA biosynthesis pathway (glycolysis, tricarboxylic acid [TCA] cycle, and Wood-Ljungdahl pathway) and amino acid biosynthesis pathway (methionine, histidine, and arginine) in the OP group relative to the HC group. This study uncovered OP-associated compositional and functional microbial alterations, providing robust insight into OP pathogenesis and aiding the possible development of a therapeutic intervention to manage the disease. IMPORTANCE Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis. However, which microbes are associated with dysbiosis and their impact on bone density and inflammation remain largely unknown due to inconsistent results in the literature. Here, we present a meta-analysis with a standard workflow, robust statistical approaches, and machine learning algorithms to identify notable microbial compositional changes influencing osteoporosis.
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The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.
Naseri, K, Saadati, S, Ghaemi, F, Ashtary-Larky, D, Asbaghi, O, Sadeghi, A, Afrisham, R, de Courten, B
European journal of nutrition. 2023;62(2):543-561
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When acute, inflammation is a necessary function of the immune system allowing the body to recognise and remove foreign stimuli. However, when chronic inflammation occurs, it can contribute to and exacerbate diseases such as type 2 diabetes (T2D). The gut microbiota and the use of probiotics has been shown to modulate processes within the body and decrease chronic inflammation, however research has not consistently shown this and an inverse relationship has been shown in some studies. This systematic review and meta-analysis aimed to determine the effect of probiotics and synbiotics on inflammation in individuals with prediabetes and T2D. A total of 32 randomised control trials were included in the meta-analysis and showed that certain, but not all inflammatory markers were reduced. Antioxidants were increased. The effect was especially pronounced in individuals with T2D as opposed to prediabetes. It was concluded that probiotics or synbiotics could be useful for individuals with T2D to reduce inflammation and reduce the risk for other associated diseases such as heart disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Probiotic and synbiotic supplementation may significantly reduce inflammation and oxidative stress, potentially lowering the risk of cardiovascular diseases in those with prediabetes and T2DM.
- These supplements may be particularly beneficial for individuals with T2DM and those who are overweight or obese.
- Incorporating probiotics and synbiotics into the diet could be a supportive strategy for improving metabolic health markers.
- The observed benefits vary depending on the type and duration of supplementation, suggesting that consistent, long-term use might be necessary to achieve noticeable health improvements.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This systematic review meta-analysis and meta-regression assessed the impact of probiotics and synbiotics on inflammation, antioxidants, oxidative stress, and adipokines in prediabetes and type 2 diabetes.
Methodology
The methodology involved searching PubMed/MEDLINE, ISI Web of Science, Scopus, and Cochrane Library databases without date or language restrictions until March 2022. Study quality was evaluated.
- Inclusion criteria: Adults 18+ with prediabetes or type 2 diabetes; interventions with probiotics or synbiotics versus placebo or other treatments; and reporting on inflammatory biomarkers, adipocytokines, and oxidative stress serum biomarkers in RCTs with parallel or cross-over designs.
Results
32 RCTs with 2074 participants were analysed, mostly in Asia (26 studies) and 5 in Europe, Africa, Oceania, and America, over 4 to 24 weeks. Dosages varied, including synbiotic bread with Lactobacillus sporogenes and inulin (1×10^8 CFU, 0.07g/g, thrice daily), 300ml/day fermented milk with L. helveticus, daily synbiotic and probiotic tablets, a probiotic mixture (120g/day), synbiotics (9g, thrice daily), multistrain probiotic yoghurt (300g/day), L. sporogenes-enriched bread (40g, thrice daily), and probiotic honey (2500mg/day). Measurements included CRP (31 RCTs), TNF-α (12 RCTs), GSH (13 RCTs), MDA (12 RCTs), TAC (11 RCTs), and NO levels (8 trials).
Effects of probiotics and synbiotics:
- significantly reduced CRP levels (-0.62 mg/L, 95% CI: -0.80 to -0.44, p < 0.001, 31 RCTs), showing greater efficacy in T2DM than prediabetes, particularly in individuals with overweight.
- TNF-α levels decreased in participants with T2D or overweight (-0.48 pg/mL, 95% CI: -0.81 to -0.15, p = 0.004, 12 RCTs).
- GSH levels significantly rose (69.80, 95% CI: 33.65 to 105.95, p < 0.001, 13 RCTs), independent of trial duration or baseline BMI.
- MDA levels were significantly reduced (-0.51, 95% CI: -0.73 to -0.30, p < 0.001, 12 RCTs) in studies lasting ≥12 weeks.
- TAC significantly increased (73.59, 95% CI: 33.24 to 113.95, p < 0.001, 11 RCTs), with more pronounced effects in longer trials and with probiotics.
- NO levels improved significantly (7.49, 95% CI: 3.12 to 11.86, p = 0.001, 9 trials) in individuals with obesity.
- Positive impacts on CRP, TNF-α, MDA, and TAC were more marked in trials ≥12 weeks.
Conclusions
Probiotic or synbiotic intake may benefit those with prediabetes and T2DM, reducing CRP, TNF-α, MDA, and enhancing TAC, GSH, NO levels, especially in T2DM individuals. Effects are stronger in individuals with overweight or obesity.
Clinical practice applications:
- Probiotic and synbiotic supplementation could be recommended to reduce inflammatory biomarkers like CRP and TNF-α, especially in individuals with T2DM.
- The improvements in oxidative stress markers, such as increased TAC and GSH and decreased MDA, support the use of probiotic and synbiotic supplements in managing oxidative stress in T2DM and prediabetes.
- Longer durations (≥12 weeks) of probiotic or synbiotic supplementation may offer a more pronounced effect on antioxidant capacity.
- The findings can guide personalised nutritional recommendations, as for example improvement in inflammation biomarkers and NO were more evident in individuals with T2DM or overweight suggesting an anti-inflammatory effect primarily in these groups. Moreover, markers related to antioxidant capacity were improved in those diagnosed with prediabetes or T2DM irrespective of BMI.
Considerations for future research:
- The beneficial effects on inflammatory and antioxidant/oxidative stress markers suggest a need for larger and longer-term studies to solidify the role of probiotics and synbiotics in benefiting chronic conditions like T2DM and prediabetes.
- There is potential for investigating the specific strains of probiotics that are most effective, considering varying outcomes observed across different studies.
- Research could explore the mechanisms by which probiotics and synbiotics exert their beneficial effects, contributing to a better understanding of gut-health interactions.
- The varying responses based on BMI categories indicate a need for personalised nutrition research to optimise probiotic therapy for individual needs.
- Future studies should consider standardising the dosage and formulation of probiotics to determine the most effective therapeutic doses and combinations.
Abstract
PURPOSE Probiotics or synbiotics consumption have been suggested to reduce the risk of cardiovascular disease (CVD) through a decline in inflammation and oxidative stress, however, the results from studies are conflicting. This study filled this knowledge gap by evaluating randomized controlled trials (RCTs) investigating probiotics or synbiotics intake on adipokines, inflammation, and oxidative stress in patients with prediabetes and type-2 diabetes mellitus (T2DM). METHODS We systematically did search up to March 2022 in PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each outcome. RESULTS A total of 32 RCTs were included in the meta-analysis. This intervention led to a significant decrease in levels of C-reactive protein (CRP) (WMD - 0.62 mg/l; 95% CI - 0.80, - 0.44; p < 0.001), tumor necrosis factor-α (TNF-α) (WMD - 0.27 pg/ml; 95% CI - 0.44, - 0.10; p = 0.002) and malondialdehyde (MDA) (WMD - 0.51 µmol/l; 95% CI - 0.73, - 0.30; p < 0.001), and also a significant increase in levels of glutathione (GSH) (WMD 69.80 µmol/l; 95% CI 33.65, 105.95; p < 0.001), total antioxidant capacity (TAC) (WMD 73.59 mmol/l; 95% CI 33.24, 113.95; p < 0.001) and nitric oxide (NO) (WMD 7.49 µmol/l; 95% CI 3.12, 11.86; p = 0.001), without significant alterations in interleukin-6 (IL-6) and adipokines levels. CONCLUSION A consumption of probiotics or synbiotics could be a useful intervention to improve cardiometabolic outcomes through a reduced inflammation and oxidative stress in patients with prediabetes and T2DM.