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The synergistic effect of herbal medicine and probiotics in pediatric functional constipation: A systematic review and meta-analysis.
Kim, E, Chang, S, Nam, J, Park, N, Min, SY
Medicine. 2024;103(7):e36899
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Paediatric functional constipation (PFC) is a prevalent gastrointestinal disorder in children. The initial approach to managing PFC involves demystification, education, toilet training, and the use of laxatives. Using laxatives can lead to various adverse effects therefore, patients with functional constipation typically adopt a self-management approach and explore complementary and alternative therapies. The aim of this study was to analyse the synergistic effect of herbal medicine (HM) combined with probiotics in the treatment of PFC, by comparing it to the use of probiotics alone. This study was a systematic review and meta-analysis of twenty-two randomised controlled trials. Results showed that the combination of HM with probiotics may yield significantly greater benefits for total effective rate when compared to probiotics alone. Furthermore, HM combined with probiotics could potentially reduce the recurrence rate by 70% compared to probiotics alone. Authors concluded that HM could potentially offer advantages in enhancing the efficacy rate and Bristol faecal score, influencing gastrointestinal peptide hormones, decreasing inflammation indicators and lowering the recurrence rate among children with functional constipation.
Abstract
BACKGROUND Pediatric functional constipation (PFC) is a prevalent and persistent gastrointestinal disorder, that requires various treatments, including alternative approaches. This review assessed the synergistic efficacy of herbal medicine (HM) and probiotics for PFC. METHODS We conducted a comprehensive search of 11 databases, including English, Chinese, and Korean databases, until June 29, 2023. The inclusion criteria were randomized clinical trials (RCTs) comparing the intervention of HM with probiotics to that of the same probiotics. Statistical analyses included calculation of the mean difference (MD), standardized MD, risk ratio (RR) with a 95% confidence interval (CI), and assessment of risk of bias using Review Manager Version 5.4 software. The Grading of Recommendations Assessment, Development, and Evaluation rating system was used to evaluate evidence quality. Potential publication bias was assessed using funnel plots, Egger test, the fail-safe N test, and Duval and Tweedie trim and fill method. RESULTS A total of 22 RCTs involving 2228 patients were included in the meta-analysis. The HM and probiotics group exhibited superior outcomes compared to the probiotics alone group in various parameters: total effective rate (RR: 1.24, 95% CI: 1.19-1.29, P < .001), Bristol fecal Score (MD: 0.80, 95% CI: 0.71-0.89, P < .001), gastrointestinal peptide hormone (motilin) (MD: 35.37, 95% CI: 24.64-64.10, P < .001), inflammation indicator (nitrous oxide) (MD: -12.45, 95% CI: -15.12 to -9.77, P < .001), minimal sensitive volume of the rectum (MD: -8.7, 95% CI: -10.91 to -6.49, P < .001), and recurrence rate (RR: 0.30, 95% CI: 0.21-0.43, P < .001). CONCLUSION The combination of HM and probiotics may exhibit a synergistic effect on PFC. Nevertheless, it is imperative to undertake rigorously planned RCTs to comprehensively evaluate the synergistic efficacy of HM and probiotics.
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Oral compound probiotic supplements can improve the quality of life for patients with lung cancer during chemotherapy: A randomized placebo-controlled study.
Wei, H, Yue, Z, Han, J, Chen, P, Xie, K, Sun, Y, Zhu, J
Thoracic cancer. 2024;15(2):182-191
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Platinum-based doublet chemotherapy occupies an important role in the management of lung cancer; however, there are treatment-associated side effects. These symptoms may deteriorate the quality of life for patients undergoing chemotherapy, and even necessitate dose reduction or discontinuation. The aim of this study was to determine whether oral compound probiotic supplements can reduce chemotherapy-related adverse effects and improve lung cancer patients' quality of life during chemotherapy. This study was a prospective, randomised, placebo-controlled, multicentre clinical study. A total of 100 lung cancer patients undergoing chemotherapy where enrolled for the study. They were randomly assigned to one of the two groups: intervention (probiotics) vs placebo. Results showed that the participants receiving probiotic supplements were significantly better in various dimensions of the overall quality of life, role function, nausea and vomiting, appetite loss, constipation, and diarrhoea relative to the placebo group. Authors concluded that compound probiotic supplements can improve the quality of life and relieve platinum-based doublet chemotherapy-induced gastrointestinal adverse reactions for lung cancer patients undergoing chemotherapy.
Abstract
BACKGROUND Chemotherapy is an important approach for lung cancer patients. The study was designed to evaluate the feasibility of the compound probiotic supplements in improving the quality of life for lung cancer patients undergoing chemotherapy. METHODS This randomized, double-blind, placebo-controlled trial enrolled chemotherapy-naive patients with lung cancer who were scheduled to receive platinum-based doublet chemotherapy. All eligible patients were randomly administered (1:1) compound probiotic supplements (group BP-1) or placebo (group C) for two chemotherapy cycles. The EORTC QLQ C30 questionnaire scores were evaluated before the first, second, and third cycles of chemotherapy. The primary endpoint was the difference in the EROTC QLQ C30 questionnaire score between the two groups after two cycles of chemotherapy. RESULTS A total of 110 patients were recruited from March 2021 to January 2022. After undergoing two cycles of chemotherapy, group BP-1 were significantly better in various dimensions of the overall quality of life, role function, nausea and vomiting, appetite loss, constipation, and diarrhea relative to group C (76.90 ± 18.31 vs. 58.89 ± 17.17; 93.33 ± 11.58 vs. 85.93 ± 15.06; 0.00 ± 0.00 vs. 27.04 ± 29.15; 6.67 ± 13.53 vs. 22.22 ± 18.80; 0.95 ± 5.63 vs. 28.15 ± 22.42; 2.86 ± 9.47 vs. 15.56 ± 16.82; p < 0.05, respectively). The incidence of nausea and vomiting, appetite loss, constipation, and diarrhea in group BP-1 was significantly lower than in group C (0% vs. 71.43%, 16.67% vs. 57.14%, 2.38% vs. 63.27%, and 7.14% vs. 42.86%, respectively, p < 0.001). CONCLUSIONS Compound probiotic supplements can improve the quality of life and relieve chemotherapy-related gastrointestinal side effects for lung cancer patients receiving platinum-based doublet chemotherapy. (Chinese Clinical Trial Registry: ChiCTR1800019269).
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The roles of the dietitian in an 18-week telephone and mobile application nutrition intervention for upper gastrointestinal cancer: a qualitative analysis.
Testa, S, Furness, K, Choi, T, Haines, T, Huggins, CE
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2023;31(4):245
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Patients with upper gastrointestinal (UGI) cancer (oesophagus, gastric, and pancreas) are vulnerable to malnutrition. Symptoms of the cancer and its treatment are barriers to usual eating patterns that contribute to unintentional weight loss. The aim of this study was to explore the patient-dietitian experience of an 18-week nutrition intervention (the TEND study) delivered using the telephone and a mobile application to people newly diagnosed with UGI cancer to elucidate the roles of the dietitian. This study was an analysis set within the TEND study (a three-arm randomised controlled trial exploring the impact of delivering an 18-week intensive nutrition intervention to patients newly diagnosed with UGI cancer). Participants were allocated to receive the intervention using either the telephone or a mobile application, myPace. Results showed that: - rapport can be built within the patient-dietitian relationship without face-to-face communication. - the roles of the dietitian were characterised by regular collaborative problem-solving to encourage empowerment, a reassuring care navigator (including anticipatory guidance), and rapport building via reliable psychosocial support. - that role limitations led to unmet needs as the dietitian was constrained by poorly managed cancer symptoms that negatively impacted oral intake and subsequently weight stability. Authors concluded that more research is needed to examine an advanced care role for dietitians in the management of nutrition impact symptoms.
Abstract
PURPOSE This study aimed to explore the patient-dietitian experience during an 18-week nutrition counselling intervention delivered using the telephone and a mobile application to people newly diagnosed with upper gastrointestinal (UGI) cancer to (1) elucidate the roles of the dietitian during intervention delivery and (2) explore unmet needs impacting nutritional intake. METHODS Qualitative case study methodology was followed, whereby the case was the 18-week nutrition counselling intervention. Dietary counselling conversations and post-intervention interviews were inductively coded from six case participants which included fifty-one telephone conversations (17 h), 244 written messages, and four interviews. Data were coded inductively, and themes constructed. The coding framework was subsequently applied to all post-study interviews (n = 20) to explore unmet needs. RESULTS Themes describing the roles of the dietitian were as follows: regular collaborative problem-solving to encourage empowerment, a reassuring care navigator including anticipatory guidance, and rapport building via psychosocial support. Psychosocial support included provision of empathy, reliable care provision, and delivery of positive perspective. Despite intensive counselling from the dietitian, nutrition impact symptom management was a core unmet need as it required intervention beyond the scope of practice for the dietitian. CONCLUSION Delivery of nutrition care via the telephone or an asynchronous mobile application to people with newly diagnosed UGI cancer required the dietitian to adopt a range of roles to influence nutritional intake: they empower people, act as care navigators, and provide psychosocial support. Limitations in dietitians' scope of practice identified unmet patient's needs in nutrition impact symptom management, which requires medication management. TRIAL REGISTRATION 27th January 2017 Australian and New Zealand Clinical Trial Registry (ACTRN12617000152325).
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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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Increased ultra-processed food consumption is associated with worsening of cardiometabolic risk factors in adults with metabolic syndrome: Longitudinal analysis from a randomized trial.
González-Palacios, S, Oncina-Cánovas, A, García-de-la-Hera, M, Martínez-González, MÁ, Salas-Salvadó, J, Corella, D, Schröder, H, Martínez, JA, Alonso-Gómez, ÁM, Wärnberg, J, et al
Atherosclerosis. 2023;377:12-23
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Evidence is increasing linking the consumption of ultra-processed foods (UPF) and an increased risk for the development of heart disease. However, there is still uncertainty surrounding how changes in UPF consumption can affect heart disease risk factors. This secondary analysis of a randomised control trial, which looked at the effects of an energy restricted Mediterranean diet in combination with exercise on the prevention of heart disease, aimed to determine how changes in UPF consumption can affect indicators of heart disease risk over a 12-month period. The results showed that high UPF consumption was associated with higher heart disease risk factors including weight, body mass index, waist circumference, diastolic blood pressure, blood sugar levels, measures of insulin resistance, and triglycerides. Further detrimental effects were seen with UPF consumption increasing, and high-density lipoprotein cholesterol decreasing. No associations were seen with systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol. It was concluded that high UPF consumption has a detrimental effect on heart disease risk. This study could be used by healthcare professionals to recommend a diet low or devoid of UPF to stay heart healthy.
Abstract
BACKGROUND AND AIMS The association between changes in ultra-processed food (UPF) consumption and cardiometabolic risk (CMR) factors remains understudied. We evaluated the association between changes in UPF consumption over 12 months of follow-up and changes in CMR factors in adults diagnosed with metabolic syndrome. METHODS We analysed data from 5373 adults (aged 55-75 years) participating in the PREDIMED-Plus trial. Diet was evaluated at baseline, 6- and 12-month visits using a validated food frequency questionnaire, and UPF consumption (in grams/day and percentage of total daily dietary intake in grams) was categorized based on NOVA classification. We used mixed-effects linear models with repeated measurements at baseline, 6 and 12 months of follow-up to assess the associations between changes in UPF consumption and changes in CMR factors adjusting for sociodemographic and lifestyles variables. RESULTS In multivariable-adjusted models, when comparing the highest versus the lowest quartile of UPF consumption, positive associations were found for several CMR factors: weight (kg, β = 1.09; 95% confidence interval 0.91 to 1.26); BMI (kg/m2, β = 0.39; 0.33 to 0.46); waist circumference (cm, β = 1.03; 0.81 to 1.26); diastolic blood pressure (mm Hg, β = 0.67; 0.29 to 1.06); fasting blood glucose (mg/dl, β = 1.66; 0.61 to 2.70); HbA1c (%, β = 0.04; 0.01 to 0.07); triglycerides (mg/dl, β = 6.79; 3.66 to 9.91) and triglycerides and glucose index (β = 0.06; 0.04 to 0.08). CONCLUSIONS Higher UPF consumption was associated with adverse evolution in objectively measured CMR factors after 12 months of follow-up in adults with metabolic syndrome. Further research is needed to explore whether these changes persist for longer periods.
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Treating asthma patients with probiotics: a systematic review and meta-analysis.
Xie, Q, Yuan, J, Wang, Y
Nutricion hospitalaria. 2023;40(4):829-838
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Asthma is a common chronic inflammatory respiratory disease, with high morbidity and mortality. Recently, the efficacy of probiotics in allergic diseases has received special attention. Experiments have shown that probiotics have a clear effect on allergic diseases. The aim of this study was to study the efficacy of probiotics in the treatment of asthma and evaluate it, so as to provide a reference for the selection of treatment options for asthma patients. This study was a systematic review and meta-analysis of ten randomised controlled trials. Results showed that probiotics can improve symptoms and airway inflammation in patients with asthma, reduce acute exacerbation of asthma, and have no significant improvement in lung function. Authors concluded that the use of probiotics in patients with asthma can improve lung inflammation and asthma symptoms, as well as reduce the number of asthma attacks.
Abstract
Objective: To evaluate the role of probiotics in the treatment of asthma patients by meta-analysis. Methods: PubMed, Embase, The Cochrane Library, Web of Science, and other databases were searched by computer, and the relevant literature on the treatment of asthma by probiotics that met the inclusion criteria was screened by manual retrieval. Meta-analysis was performed using Revman 5.4 software and the combined effect was evaluated by odds ratio (OR) or mean difference (MD) and 95 % confidence interval (CI). Results: a total of ten references were included, all of which were randomized controlled studies, and a total of 1,101 people were investigated. Fractional exhaled nitric oxide (FeNO) (MD = -7.17, 95 % CI: -12.81, -1.54), asthma symptom severity (MD = -0.07, 95 % CI: -0.10, -0.04), Childhood Asthma Control Test (CACT) (MD = 2.26, 95 % CI: 1.14, 3.39), and the number of acute episodes of asthma (OR = 0.30, 95 % CI: 0.19, 0.47) in the probiotics group were better than those in the control group. There was no significant difference in forced expiratory volume in the first second (FEV1) (MD = 0.11, 95 % CI: -0.05, 0.26) and FEV1/FVC (%) (MD = 0.32, 95 % CI: -1.48, 2.12). Conclusion: the use of probiotics in patients with asthma can improve lung inflammation and asthma symptoms, reduce the number of asthma attacks, and have no effect on lung function. Objetivo: evaluar el papel de los probióticos en el tratamiento de pacientes con asma mediante metaanálisis. Métodos: se realizaron búsquedas informáticas en PubMed, Embase, The Cochrane Library, Web of Science y otras bases de datos, y se examinó la literatura relevante sobre el tratamiento del asma con probióticos que cumplía con los criterios de inclusión mediante recuperación manual. El metaanálisis se realizó con el software Revman 5.4 y el efecto combinado se evaluó mediante la razón de probabilidades (OR) o diferencia media (MD) y el intervalo de confianza (IC) del 95 %. Resultados: se incluyó un total de diez referencias, todas ellas estudios controlados aleatorios, y se investigó un total de 1.101 personas. El óxido nítrico exhalado (FeNO) (MD = -7,17, IC 95 %: -12,81, -1,54), la gravedad de los síntomas del asma (MD = -0,07, IC 95 %: -0,10, -0,04), la Prueba de Control del Asma (CACT-ACT) (MD = 2,26, IC 95 %: 1,14, 3,39) y el número de episodios agudos de asma (OR = 0,30, IC 95 %: 0,19, 0,47) en el grupo de probióticos fueron mejores que en el grupo de control. No hubo diferencia significativa en volumen espiratorio forzado en el primer segundo (FEV1) (DM = 0,11, IC 95 %: -0,05, 0,26) y FEV1/FVC (%) (DM = 0,32, IC 95 %: -1,48, 2,12). Conclusión: el uso de probióticos en pacientes con asma puede mejorar la inflamación pulmonar y los síntomas del asma, reducir el número de ataques de asma y no tener efecto sobre la función pulmonar.
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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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The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review.
Zhang, T, Zhang, J, Duan, L
Nutrients. 2023;15(7)
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Inflammatory bowel disease (IBD), largely classified as Crohn’s disease (CD) or ulcerative colitis (UC), is a chronic intestinal inflammatory disorder mediated by genetic, immune, microbial, and environmental factors. The aim of this study was to summarise the efficacy of different genetically modified probiotics compared to wild-type probiotics in the treatment of IBD in animal models and patients and to investigate the specific effects and main mechanisms involved. This study was a systematic review of forty-five preclinical studies and one clinical study. Results showed a protective effect of genetically modified organisms (gm) probiotics in colitis. Several protective mechanisms have been identified: reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of the activity of oxidative stress in the colon, improvement of intestinal barrier integrity, modulation of the diversity and composition of gut microbiota, and production of favourable metabolites, including short-chain fatty acids, by beneficial bacteria. Authors concluded that gm probiotics are more effective and safer than wild-type probiotics, to facilitate clinical translation.
Expert Review
Conflicts of interest:
None
Take Home Message:
Conclusions of this review were largely based on mouse models and although treatment using probiotics is generally considered safe in humans, with only minor side-effects (flatulence), practitioners need to be aware that in an IBD population the use of GM formulations might not be completely without risk.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This paper summarises the efficacy of specific genetically modified (GM) probiotic formulations for Inflammatory Bowel Disease (IBD) when compared to wild type probiotics. The aim was to ascertain what specific effects and mechanisms such probiotics have on IBD symptomatology.
Methods
- A total of 46 published articles were included; 45 mouse experimental models (induced acute or chronic colitis) (n=15-130) and 1 human IBD population clinical trial (n=10)
- The effect of GM probiotics were compared to placebo and wild-type probiotics in trials including preclinical studies, randomised controlled trials and cohort studies
- Animals received probiotics via gastric gavage (105 - 4 x 1012 CFU) for 3-6 weeks
- The human placebo-uncontrolled trial lasted 7 days and patients received 10 GM capsules of L.lactis (1 x 1010 CFU) twice daily.
Results
- GM probiotics that secrete immunoregulatory cytokines such as IL-10 appear to reduce intestinal damage
- The human trial using GM L.lactis resulted in 5 patients who went into complete clinical remission (CDAI, <150) with 3 patients exhibiting a clinical response (decrease in CDAI, >70). with only minor adverse events (flatulence)
- However, human cytokines that promote intestinal barrier function and epithelial restitution were not enhanced with oral administration of probiotics
- Two studies concluded that GM L.lactis and S.boulardii, that secrete atrial natriuretic peptide, might be the most effective options in supporting colitis
- GM L.casei resulted in faster recovery from weight loss in acute colitis models
- Superoxide dismutase (SOD) producing GM L.fermentum increased SOD activity by almost eightfold compared to the wild type
- GM Lact. fermentum furthermore showed a higher survival rate and lower disease activity index (P <0·05) in colitis models
- GM L.lactis improved gut microbial composition and GM S.cerevisiae improved microbial diversity whilst reducing the Firmicutes to Bacteroides ratio
- GM E.coli significantly reduced weight loss, colon shortening plus lower disease activity and histological changes (P < 0.05).
Conclusion
Despite the heterogeneity of the trials, GM probiotics appear to play a notable part in ameliorating IBD symptomatology and disease severity when compared to wild-type probiotics. Human efficacy and potential adverse effects require more in-depth trials to ascertain safety and optimal dosages.
Clinical practice applications:
- Probiotics species used in the trials included S.thermophilus, E.coli, L.lactis, B.ovatus, S.boulardii, L.fermentum, B.longhum, L.casei, L.plantarum, and S.cerevisiae. Wild-types of some of these are already available to use in clinical practice
- Note that oral administration in the human trial showed no significant health outcome, therefore efficacy and safety need to be ascertained on an individual patient level
- Colonisation of beneficial bacteria in the gut of IBD patients might be difficult and any form of supplementation therefore needs to be closely monitored.
Considerations for future research:
- More evidence is needed to demonstrate that GM probiotic formulations result in significantly improved outcomes when compared to wild-types
- Future randomised placebo-controlled trials need to include larger cohorts to determine supplement efficacy
- Longer periods of intervention are needed to confirm efficacy, safety, and tolerance for both Crohn’s Disease and Colitis
- Optimal GM probiotic formulation, doses, and means of application need to be identified.
Abstract
BACKGROUND Many preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD). OBJECTIVE This systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms. METHODS PubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical. RESULTS Forty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn's disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients. CONCLUSIONS Gm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.
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The Effectiveness of Probiotics in Treating Food and Cow's Milk Allergies among Pediatric Age Group: A Meta-analysis of Randomized Controlled Trials.
Feng, H, Wu, Y
Iranian journal of allergy, asthma, and immunology. 2023;22(2):124-137
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Food allergy is defined as any adverse health effect that occurs due to a specific immune response that usually repeats every time after a specific food exposure. The aim of this study was to determine the effectiveness of administering probiotics as a supplement to treat food and cow’s milk allergies among children less than 5 years old as compared to placebo. This study was a systematic review and meta-analysis of twenty randomised controlled trials. Results showed that probiotic supplementation significantly improved food allergy symptoms when compared to a placebo. Furthermore, subgroup analysis also revealed that the effect remained favourable in all subgroups. Authors concluded that probiotics may be useful in reducing food allergies among children under 5. However, they also point out that more systematic reviews are needed to assess the safety and side effect pattern of these probiotics.
Abstract
The global prevalence of allergies is on the rise. Food allergies are of special concern among children under 5 years of age, leading to morbidity and mortality. Though the standard management is avoidance, probiotics are being used widely to prevent and treat food allergies. We aimed to determine the effect of probiotics as a therapeutic option for controlling food and cow's milk allergy among children under 5 years of age. A systematic search of electronic medical literature databases was conducted. We included all eligible randomized controlled trials available from inception until May 2021. The primary outcome of interest was the relief of allergic symptoms, while the secondary outcome was the induction of tolerance. Two investigators undertook the literature search, screening, data extraction, and quality appraisal independently. Data analysis and synthesis were performed using STATA 14 software. Subgroup analysis was performed for the duration of use and follow-up, and the age category of children included in the outcome were done. Twenty trials involving 4043 pediatric patients with food allergies were included in the review. Subgroup analysis also revealed that probiotics were effective in treating food allergies across the various subgroups included in the model. Around 15 trials reported our primary outcome, relief of symptoms, as a binary variable, which was pooled to obtain a risk ratio of 0.86 (95% confidence interval [CI], 0.77-0.95), with very low heterogeneity (I2 7.7%). Six trials were included for the secondary outcome of interest, which gave an imprecise pooled estimate of 1.29 (95% CI, 0.98-1.70) with significant heterogeneity (I2 7). Thus, we conclude that probiotics can serve as a vital therapeutic option in tackling food allergies among children less than 5 years of age. Further larger studies exploring the effectiveness of individual strains and their safety pattern are essential.
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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.