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Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials.
Shu, Q, Kang, C, Li, J, Hou, Z, Xiong, M, Wang, X, Peng, H
PloS one. 2024;19(1):e0296733
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The gut microbiome is thought to play a role in thyroid disorders, mediated by regulating iodine uptake, degradation and enterohepatic cycling of thyroid hormones, and differences in microbiome composition between patients with thyroid disorders and healthy individuals have been observed. The aim of this systematic review and meta-analysis was to evaluate the effect of pro-, pre- and synbiotics on thyroid function (thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) and thyroid stimulating hormone receptor antibody (TRAb)) in patients with and without thyroid disorders. 8 randomised controlled trials including 367 participants were included in the review and meta-analysis. Neither pro-, pre- nor synbiotics had a significant effect on TSH, fT4 or fT3 but pre- and probiotics lead to a significant reduction in TRAb in patients with Graves’ disease.
Abstract
BACKGROUND Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels. METHODS We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement. RESULTS A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: -0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: -0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: -0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found. CONCLUSIONS Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves' disease.
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Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults.
van der Spoel, E, van Vliet, NA, Poortvliet, RKE, Du Puy, RS, den Elzen, WPJ, Quinn, TJ, Stott, DJ, Sattar, N, Kearney, PM, Blum, MR, et al
The Journal of clinical endocrinology and metabolism. 2024;109(3):e1167-e1174
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With increasing age, circulating levels of thyroid stimulating hormone (TSH) generally rise, accompanied by a higher prevalence of subclinical hypothyroidism. Subclinical hypothyroidism is defined as an elevated TSH level while the serum free T4 (fT4) concentration is within the normal range. The aim of this study was to investigate the incidence of spontaneous normalisation of TSH levels and identify determinants of normalisation in a large group of adults aged 65 years and older with (persistent) subclinical hypothyroidism. This study was a longitudinal study that pooled data from 2 randomised, double-blind, placebo-controlled parallel-group clinical trials. Results showed that 60.8% of the older adults with biochemical subclinical hypothyroidism based on at least 1 elevated TSH measurement, TSH levels had returned to the normal range without intervention after a median follow-up of 1 year. Subsequently, TSH levels had still normalised after 1 year in 39.9% of older adults with persistent subclinical hypothyroidism. Younger age, female sex, lower initial TSH level, higher normal initial fT4 level, the absence of thyroid peroxidase antibodies, and a second measurement in summer were independent determinants for TSH normalisation. Authors concluded that since TSH levels spontaneously normalised in a large proportion of older adults with subclinical hypothyroidism, a third measurement is recommended before considering treatment.
Abstract
CONTEXT With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. OBJECTIVE To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism. DESIGN Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial). SETTING Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. PARTICIPANTS The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. MAIN OUTCOME MEASURES Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. RESULTS In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. CONCLUSION Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment. TRIAL REGISTRATION ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.
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Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes.
Yang, J, Yang, X, Wu, G, Huang, F, Shi, X, Wei, W, Zhang, Y, Zhang, H, Cheng, L, Yu, L, et al
Cell metabolism. 2023;35(9):1548-1562.e7
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Distal symmetric polyneuropathy (DSPN) is the most common complication associated with diabetes, which can lead to pain, numbness, and weakness or tingling in the limbs or parts of the body. There are no cures for DSPN only drugs to manage symptoms, highlighting a need for further research. Recently it has been shown that the gut microbiota of individuals with DSPN differs to that of healthy individuals, but it is unclear as to the significance of this. This randomised control trial aimed to determine the effect of transplanting faecal microbiota from healthy individuals into those with DSPN. The results showed that DSPN was associated with a decreased abundance of beneficial gut bacteria and an increased abundance of pathogenic bacteria. Furthermore, compared to placebo, DSPN was alleviated in all 22 patients who received a faecal microbiota transplant from healthy subjects. There was an increase in gut microbiota associated with the production of beneficial short chain fatty acids and a decrease in toxin production. It was concluded that dysbiosis in the gut microbiota contributes to DSPN, which can be alleviated by faecal microbial transplant from healthy individuals. This study could be used by healthcare professionals to understand that the gut microbiota has an important role in DSPN. Further larger studies would be warranted before recommending faecal microbial transplant to individuals with this disorder.
Abstract
The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.
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Sustained Diet-Induced Remission in Pediatric Crohn's Disease Is Associated With Kynurenine and Serotonin Pathways.
Ghiboub, M, Boneh, RS, Sovran, B, Wine, E, Lefèvre, A, Emond, P, Verburgt, CM, Benninga, MA, de Jonge, WJ, Van Limbergen, JE
Inflammatory bowel diseases. 2023;29(5):684-694
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Crohn’s disease (CD) is an inflammatory bowel disease associated with alterations in intestinal tryptophan metabolism, in particular with increases in metabolites of the kynurenine pathway and decreased metabolites of the serotonin pathway. The aim of this 12-week randomised clinical study was to evaluate the effect of CD exclusion diet with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) on intestinal tryptophan metabolism (as measured in faeces) in 43 children with mild-to-moderate CD. 13 of 15 patients on CDED+PEN and 9/13 on EEN achieved remission at week 6, and 8/9 and 6/9 patients, respectively, maintained remission at 12 weeks. Some kynurenine pathway metabolites decreased and some serotonin metabolites increased, in patients who achieved induction and maintenance of remission. These changes were similar in both intervention groups. On the other hand, in patients on EEN who did not go into remission, these changes were not observed. The authors concluded that further studies are warranted to inform whether there is a causal link and to refine nutritional interventions.
Abstract
BACKGROUND Both the Crohn's disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn's disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and changes in tryptophan metabolism pathways. Here, we characterize the changes in several fecal tryptophan metabolites induced by CDED+PEN or EEN and their association with remission. METHODS A total of 21 tryptophan metabolites were quantified in fecal samples from a 12-week prospective randomized trial with CDED+PEN or EEN for induction of remission in mild to moderate pediatric Crohn's disease. Tryptophan metabolites at week 0 (W0), W6, and W12 of 73 samples were quantitatively measured by liquid chromatography coupled with triple quadrupole mass spectrometry, and data were analyzed according to clinical groups of baselines (W0), induced remission at W6, no remission, sustained remission at W12, and nonsustained remission. RESULTS Reduction in components of the kynurenine pathway, such as kynurenine and quinolinic acid, were strongly associated with induced remission with both CDED+PEN and EEN, which were maintained in sustained remission. Specific serotonin pathway metabolites, such as melatonin, N-acetylserotonin, and 5-OH-tryptophan, were significantly increased in fecal samples from patients maintaining remission at W12 with both CDED+PEN and EEN. Importantly, in samples from patients failing to sustain remission, no changes were observed. Remission induction with EEN differs from CDED+PEN, particularly the moderate effects on indole pathway metabolites. The ratios of kynurenine and melatonin and quinolinic acid and melatonin perform well as markers for sustained remission. CONCLUSIONS The reduction in specific kynurenine pathway compounds and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. Further studies are warranted to assess causality and the association of these metabolites with specific diet and lifestyle factors, affecting sustained clinical remission. We show that fecal tryptophan metabolites are associated with remission following dietary therapy in a prospective clinical trial of pediatric Crohn’s disease patients. Our study shows that reduction in some kynurenine pathway metabolites and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. These compounds may play a role in mediating the mechanism of action of dietary therapy.
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study.
Yu Chen, H, Dina, C, Small, AM, Shaffer, CM, Levinson, RT, Helgadóttir, A, Capoulade, R, Munter, HM, Martinsson, A, Cairns, BJ, et al
European heart journal. 2023;44(21):1927-1939
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Aortic stenosis (AS) is a form of heart disease that is an abnormal narrowing of the aortic valve in the heart, which restricts blood flow. Although being over the age of 75 appears to increase the risk for development, it is unclear as to who else may be at risk. A better understanding of genetic factors, which may be involved in its development could better help to identify those at risk. This meta-analysis of 10 cohort studies aimed to determine genetic contributors to AS and possible mechanisms involved. The results showed that 15 different gene variations were strongly associated with AS including those in the CELSR2-SORT1, NLRP6, LPA and SMC2 genes. Interestingly some of these genes were also identified in individuals with African and Latin American ancestry. It was concluded that these genes, many of which are associated with hardening of the arteries, altered lipid metabolism, excess storage of fat, and inflammation may all contribute to AS. This study could be used by healthcare professionals to understand that there are specific genetic contributors to the development of AS and that in the future we may be able to target these to identify high-risk individuals and use them in therapeutic management.
Abstract
AIMS: Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND RESULTS A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. CONCLUSION Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.
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Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Jamshidi, P, Farsi, Y, Nariman, Z, Hatamnejad, MR, Mohammadzadeh, B, Akbarialiabad, H, Nasiri, MJ, Sechi, LA
International journal of molecular sciences. 2023;24(19)
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Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder the cause of which is not yet fully elucidated. Probiotics, prebiotics and dietary changes have been shown to mitigate IBS symptoms whilst the results from studies of faecal microbiota transplants (FMT) have been inconsistent. The aim of this systematic review and meta-analysis of double-blind, randomised controlled trials (RCT) was to evaluate the efficacy and safety of FMT in IBS. 7 RCTs with a low risk of bias and no publication bias were included in the meta-analysis. Overall, no statistically significant effect was observed. A subgroup analysis by treatment modality showed that benefits were seen with lower GI administration of a single dose of multiple-donor FMT. Abdominal pain, nausea, diarrhoea and bloating were the most common adverse events, with no severe or critical adverse events reported. The authors call for larger and longer clinical trials to fill existing knowledge gaps.
Abstract
Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.
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Irritable Bowel Syndrome Is Not Associated with an Increased Risk of Polyps and Colorectal Cancer: A Systematic Review and Meta-Analysis.
Vichos, T, Rezaie, A, Vichos, P, Cash, B, Pimentel, M
Digestive diseases and sciences. 2023;68(6):2585-2596
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Colorectal cancer (CRC) is one of the most common cancers and adenomatous colorectal polyps (CRP) are a risk factor for developing CRC. The potential role of functional disturbances seen in irritable bowel syndrome (IBS) for the development of CRC are not yet clear. The aim of this systematic review and meta-analysis was to evaluate the occurrence of CRC and CRP in IBS patients. 14 cohort studies with a total of 654,764 IBS patients and 2,277,195 controls and six cross-sectional studies with 26,641 IBS patients and 87,803 controls were included in the review. Based on the pooled data from 5 cross-sectional studies, IBS patients had a significantly lower occurrence of CRP (by 71%). CRC risk was also reduced but this did not reach statistical significance. Only four of the 14 cohort studies were included in the meta-analysis and, again, CRC risk was lower in IBS patients but this was not statistically significant.
Abstract
OBJECTIVES Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients. METHODS Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models. RESULTS Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I2 = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I2 = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]). CONCLUSION Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development.
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COVID-19-associated lung weakness (CALW): Systematic review and meta-analysis.
Redruello-Guerrero, P, Ruiz-Del-Pino, M, Jiménez-Gutiérrez, C, Jiménez-Gutiérrez, P, Carrascos-Cáliz, A, Romero-Linares, A, Láinez Ramos-Bossini, AJ, Rivera-Izquierdo, M, Cárdenas-Cruz, A
Medicina intensiva. 2023;47(10):583-593
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During the Covid-19 pandemic there was an increase in the number of individuals experiencing a collapsed lung, otherwise known as a pneumothorax (PNX) or pneumomediastinum (PNMD). The reasons for increased PNX are unclear and this systematic review and meta-analysis of 12 studies including 4901 individuals with Covid-19 aimed to determine what may be responsible for this. The results showed that 1629 individuals experienced a PNX and 253 a PNMD, and death was higher amongst those who developed PNX and PNMD. There were strong associations between the occurrence of PNX and PNMD and death. It was concluded that PNX and PNMD significantly increased the risk of dying in individuals with Covid-19 and it was proposed that the term Covid-19-Associated Lung Weakness (CALW) should be applied to those who experience PNX of PNMD. There was some concern that the quality of the research used was very low and so this study could be used by healthcare professionals to understand that PNX and PNMD in Covid-19 patients should be closely monitored and managed.
Abstract
OBJECTIVES To assess mortality and different clinical factors derived from the development of atraumatic pneumothorax (PNX) and/or pneumomediastinum (PNMD) in critically ill patients as a consequence of COVID-19-associated lung weakness (CALW). DESIGN Systematic review with meta-analysis. SETTING Intensive Care Unit (ICU). PARTICIPANTS Original research evaluating patients, with or without the need for protective invasive mechanical ventilation (IMV), with a diagnosis of COVID-19, who developed atraumatic PNX or PNMD on admission or during hospital stay. INTERVENTIONS Data of interest were obtained from each article and analyzed and assessed by the Newcastle-Ottawa Scale. The risk of the variables of interest was assessed with data derived from studies including patients who developed atraumatic PNX or PNMD. MAIN VARIABLES OF INTEREST Mortality, mean ICU stay and mean PaO2/FiO2 at diagnosis. RESULTS Information was collected from 12 longitudinal studies. Data from a total of 4901 patients were included in the meta-analysis. A total of 1629 patients had an episode of atraumatic PNX and 253 patients had an episode of atraumatic PNMD. Despite the finding of significantly strong associations, the great heterogeneity between studies implies that the interpretation of results should be made with caution. CONCLUSIONS Mortality among COVID-19 patients was higher in those who developed atraumatic PNX and/or PNMD compared to those who did not. The mean PaO2/FiO2 index was lower in patients who developed atraumatic PNX and/or PNMD. We propose grouping these cases under the term COVID-19-associated lung weakness (CALW). OBJETIVO Evaluar la mortalidad y diversos factores clínicos derivados del desarrollo de neumotórax (NTX) y/o neumomediastino (NMD) atraumáticos en pacientes críticos como consecuencia de la debilidad pulmonar asociada a COVID-19 (DPAC). DISEÑO: Revisión sistemática con metaanálisis. ÁMBITO Unidad de Cuidados Intensivos (UCI). PARTICIPANTES Investigaciones originales en las que se evaluase a pacientes, con o sin necesidad de ventilación mecánica invasiva (VMI), con diagnóstico de COVID-19 que hubiesen desarrollado NTX o NMD atraumáticos al ingreso o durante su estancia hospitalaria. INTERVENCIONES Se obtuvieron los datos de interés de cada artículo que fueron analizados y evaluados por la Escala Newcastle-Ottawa. El riesgo de las variables de interés principales se evaluó por los datos derivados de los estudios que incluyeron a pacientes que desarrollaron NTX o NMD atraumáticos. VARIABLES DE INTERÉS PRINCIPALS Mortalidad, estancia media en la UCI y PaO2/FiO2 media en el momento diagnóstico. RESULTADOS Se recogieron datos de 12 estudios longitudinales. En el metaanálisis se incluyeron datos de un total de 4.901 pacientes, entre los cuales 1.629 presentaron un episodio de NTX y 253 de NMD atraumáticos. A pesar de encontrar asociaciones significativamente fuertes, la alta heterogeneidad entre los estudios hace que la interpretación de los resultados deba hacerse con cautela. CONCLUSIONES La mortalidad de los pacientes COVID-19 fue mayor en los que desarrollaron NTX y/o NMD atraumáticos con respecto a los que no lo hicieron. La media del índice PaO2/FiO2 fue menor en los pacientes que desarrollaron NTX y/o NMD atraumáticos. Proponemos agrupar bajo el término deDPAC estos casos.
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Effects of Probiotics in Adults with Gastroenteritis: A Systematic Review and Meta-Analysis of Clinical Trials.
Mitra, AK, Asala, AF, Malone, S, Mridha, MK
Diseases (Basel, Switzerland). 2023;11(4)
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Gastroenteritis is a major cause of morbidity and mortality globally and symptoms can range from mild to life-threatening. Some studies have suggested benefits of probiotics in the treatment of gastroenteritis in children whilst in adults, results are inconsistent. The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics on acute and chronic gastroenteritis in adults. 35 clinical trials were included in the systematic review and 22 in the meta-analysis. Of these, 23 dealt with inflammatory bowel disease, 5 with pouchitis, 3 with antibiotic-induced diarrhoea, 2 with Helicobacter pylori infection and one each with diverticulitis and acute watery diarrhoea. 27 (77%) of studies showed some benefits of probiotic administration. The meta-analysis of 22 studies did not show a statistically significant benefit of probiotics. Although statistical analysis showed the studies to be homogenous, the authors point out that studies differed widely in aetiologies and probiotics used. A subgroup analysis of 8 studies in patients with ulcerative colitis also showed no benefit. In all studies, probiotics were well tolerated and no adverse side effects were reported. The authors concluded that further research is needed to help identify the most appropriate use of probiotics for the different types of gastroenteritis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For chronic inflammatory gastroenteritis conditions in adults, probiotics were effective in treating and preventing relapse
- In ulcerative colitis, probiotics were not effective and adverse events outweighed the benefits
- No safety concerns were found for probiotic use in any studies
- Aetiologies, disease severity and duration as well as the type of probiotics used were widely diverse.
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
To date, evidence has been mixed for probiotic effectiveness in gastrointestinal syndromes associated with gastroenteritis. The aim of this study was to review current evidence on the effect of probiotics on gastroenteritis in adults.
Methods
This was a systematic review (n=35; total sample size 4577, median 44) and meta-analysis (n=22) of randomised controlled trials. Quality was assessed using CADIMA as per a rating scale (0 to 4) and standards of critical appraisal.
Results
All 35 studies on gastroenteritis included participants with chronic diarrhoea of diverse aetiologies such as IBD, antibiotic-associated, except one which had acute watery diarrhoea.
51% (n=18) of studies assessed the effects of probiotics in the treatment of ulcerative colitis (UC) and Crohn's disease (CD). 60% (n=21) used multiple strains of probiotics while the rest used single strains. Lactobacilli, Bifidobacteria, Escherichia and Streptococcus were the most common and only a few studies administered probiotics with another conventional treatment.
19 studies (55%) rated highly in terms of quality while 15 (43%) scored moderately. The majority (63%) of the 27 studies where probiotics were shown to be effective were of high quality.
Systematic review results:
- 27/53 studies (77%) showed a favourable response after using probiotics (resolution, improvement, remission or no relapse), mostly in patients with IBDs
- 7 studies (20%) found probiotics to be ineffective
- 1 study was inconclusive
- Multiple strain probiotics (VSL #3) was found to be most effective in IBD
- All administered probiotics were well tolerated with no adverse side effects although caution in immunocompromised patients was mentioned in several studies.
The meta-analysis results:
- Overall effectiveness for 22 studies (p=0.37) highlighted there was not enough evidence that the intervention was more protective than controls.
- Probiotics were not effective in UC (p = 0.28), and adverse events caused by probiotics may outweigh the benefits in studies with UC patients.
Conclusion
While benefits of effectiveness were found for probiotic use in gastroenteritis in adults, results from the systematic review and meta-analysis showed a mixed effect.
Clinical practice applications:
- Based on the systematic review, probiotics may be an effective treatment or adjuvant treatment for gastroenteritis but ineffective for around 20% of patients
- It is worth noting that combined therapy with standard treatment showed effective results
- Beneficial effects of probiotics in other key clinical outcomes including disease prevention, relapse, quality of life, morbidity were found
- While the results are interesting it is difficult to apply them in practice as the type of probiotics used were widely different as were the causes, severity and duration of gastroenteritis.
Considerations for future research:
- Further and larger studies would be beneficial to understand the benefits of probiotics in terms of single therapy or in combination with standard treatment particularly for UC, CDs, gastroenteritis not due to viral infection
- Individual-level data instead of aggregated data could give a better idea of effectiveness of probiotics in the future
- In this study aetiologies and the type, dosage, duration of probiotics used were widely diverse therefore systematic reviews and meta-analysis on specific conditions, specific probiotic strains and combinations would be beneficial.
Abstract
Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions is inconclusive and conflicting. The aim of this study was to review the existing literature on the effects of probiotics on gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases, such as PubMed, Google Scholar, MEDLINE and Scopus databases, were searched for the data. The study followed standard procedures for data extraction using a PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was performed. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective, and 1 study's results were inconclusive. The meta-analysis did not demonstrate any significant protective effects of probiotics. Having a τ2 value of zero and I2 of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.
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Effect of supplementation with probiotics or synbiotics on cardiovascular risk factors in patients with metabolic syndrome: a systematic review and meta-analysis of randomized clinical trials.
Chen, T, Wang, J, Liu, Z, Gao, F
Frontiers in endocrinology. 2023;14:1282699
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Plain language summary
Metabolic syndrome (metS) is characterised by insulin resistance, dyslipidaemia, central obesity and/or high blood pressure and is a significant risk factor for cardiovascular disease and type 2 diabetes mellitus. MetS is associated with an imbalanced microbiome and some but not all studies have shown benefits of supplementation with probiotics. The aim of this systematic review and meta-analysis of randomised controlled trials was to evaluate the effects of pro- or synbiotics on cardiovascular risk factors (body mass index, LDL cholesterol, fasting blood glucose and systolic blood pressure) in patients with metS. 11 studies were included in the review of which 7 were judged to have a low risk of bias, whilst risk of bias was unclear in 4 articles. The meta-analysis found that pro- or synbiotics have a positive effect on body mass index, LDL cholesterol and fasting blood glucose but not on systolic blood pressure. Subgroup analysis of pro- and synbiotics separately also found no effects on systolic blood pressure.
Abstract
PURPOSE The effectiveness of probiotics or synbiotics in adults with metabolic syndromes (MetS) remains controversial, this meta-analysis will further analyze the effects of probiotics or synbiotics on cardiovascular factors in adults with MetS. METHODS We searched Web of Science, PubMed, Embase, Cochrane Library and other databases for randomized controlled trials (RCTs) on the effects of probiotics or synbiotics on MetS in adults up to July 2023, and used RevMan 5.4.0 software for statistical analysis. RESULTS This analysis included eleven RCTs (n = 608 participants), and the results showed that compared with the control group, supplementation with probiotics or synbiotics reduced body mass index (weighted mean difference, WMD = -0.83, 95% CI = [-1.21, -0.44], P <0.0001, n = 9), low-density lipoprotein (LDL-c) (standard mean difference, SMD = -0.24, 95% CI = [-0.41, -0.08], P = 0.004, n = 10), fasting blood glucose (FBG)(SMD = -0.17, 95% CI = [-0.33, -0.01], P = 0.03, n = 11), but had no beneficial effect on systolic blood pressure (SBP) (WMD = 1.24, 95% CI = [-2.06, 4.54], P = 0.46, n = 8) in MetS patients. CONCLUSION Supplementation with probiotics or synbiotics can reduce BMI, LDL-c, FBG in patients with MetS, but our findings did not demonstrate a favorable effect on reducing SBP. Future studies with larger samples and longer intervention periods are needed.