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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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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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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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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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Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.
Scheffers, LE, Vos, IK, Utens, EMWJ, Dieleman, GC, Walet, S, Escher, JC, van den Berg, LEM
Journal of pediatric gastroenterology and nutrition. 2023;77(2):214-221
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Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract, characterised by periods of remission and relapse of symptoms. The aim of this study was to assess the effects of a tailored lifestyle intervention on physical fitness (maximal and submaximal exercise capacity, strength, and core stability), the patient-reported outcomes (quality of life, fatigue, and fear), clinical disease activity, and nutritional status. This study was a prospective single-centre randomised semi-crossover-controlled trial. Children were randomized into group A (start exercise) or group B (start control period). Results showed improved physical fitness, quality of life, and parent-reported fatigue. Additionally, a combination of lower clinical disease activity scores accompanied by fewer IBD symptoms suggests positive effects on intestinal inflammation. Authors concluded that based on the findings of their study, children and adolescents with IBD should be motivated and supported to acquire and maintain a healthy lifestyle.
Expert Review
Conflicts of interest:
None
Take Home Message:
- IBD is a chronic inflammatory disease of the gastrointestinal tract, characterised by periods of abdominal pain, severe diarrhoea, and fatigue
- This clinical trial suggests that a 12-week program of physical training plus personalised healthy dietary advice may improve physical fitness, quality of life, and fatigue in children with IBD.
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
A randomised semi-crossover controlled trial was conducted to investigate the impact of a 12-week lifestyle program (3 physical training sessions per week plus personalised healthy dietary advice) in children with Inflammatory Bowel Disease (IBD).
Method
- Sixteen children with a median age of 15 [IQR: 12–16]) that were diagnosed with IBD (CD, UC, or IBD-unclassified) were randomized to group A (start exercise) or group B (start control period). Group A started the intervention immediately after the first assessment and did not have a control period. Group B started after a control period (this was planned to last for 6 weeks but due to the COVID-19 lockdown extended to 6 months)
- The lifestyle intervention lasted 12 weeks and consisted of 3 physiotherapist-supervised training sessions per week, lasting 60 minutes each. In addition, all participants received a recommended caloric intake per day based on measured rest energy expenditure and a brochure regarding healthy diet in children
- Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (faecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition)
- A total of 15 out of 16 participants (93%) completed the program, one patient dropped out after one training session due to motivational problems.
Results
The primary findings of this study were as follows:
- While medical treatment remained unchanged, Paediatric Crohn's Disease Activity Index decreased versus the control period (15 [3–25] vs 2.5 [0–5], P = 0.012)
- The number of patients in clinical remission increased from 5 to 12 (P < 0.001), compared to the control period
- Quality of life (IMPACT-III) improved on 4 out of 6 domains and the total score (+13 points) versus the control period including a large improvement in bowel-related symptoms, P= 0.029)
- Fecal calprotectin decreased, but not compared to the control period, mainly due to relatively large intra-patient fluctuations (400 μg/g [57.1–1662.7] vs 128 μg/g [23.8–642.3], P = 0.016)
- Parents reported an improvement in the quality of life versus the control period on the child health questionnaire and total fatigue score (PedsQoL • Multidimensional Fatigue Scale) (+14 points, P = 0.048)
- Walking distance improved after the 12-week program, compared to the control period (P = 0.001).
Conclusion
This study revealed that a 12-week physical training program and personalised dietary advice improved bowel symptoms, quality of life, and fatigue in children with IBD.
Clinical practice applications:
- The mechanism behind the anti-inflammatory effects of exercise has not been clarified
- Multiple theories have been suggested in previously published studies such as a reduced release of adipokines due to less visceral fat, increased secretion of anti-inflammatory cytokines such as interleukin (IL)-6, and reduced transient stool time
- This clinical trial demonstrated that a 12-week program of physical training sessions plus personalised healthy dietary advice resulted in improved physical fitness, quality of life, and parent-reported fatigue.
Considerations for future research:
- A sample size calculation was not provided in the study report and it is therefore assumed that the sample size of 16 children in this trial was too small to draw a definite conclusion. A larger study over a longer period is therefore needed across diverse age and ethnic population groups to draw better conclusions
- This study did not measure mucosal inflammation before and after the intervention due to the invasive nature of the procedure. It would however be useful that future research investigate this to gain more insight into the effect of lifestyle interventions on IBD.
Abstract
OBJECTIVES Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD. METHODS This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO 2 ) was the primary endpoint; all others were secondary endpoints. RESULTS Fifteen patients (median age 15 [IQR: 12-16]) completed the program. At baseline, peak VO 2 was reduced (median 73.3% [58.8-100.9] of predicted). After the 12-week program, compared to the control period, peak VO 2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3-25] vs 2.5 [0-5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period. CONCLUSIONS A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.
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B-vitamins, related vitamers, and metabolites in patients with quiescent inflammatory bowel disease and chronic fatigue treated with high dose oral thiamine.
Bager, P, Hvas, CL, Hansen, MM, Ueland, P, Dahlerup, JF
Molecular medicine (Cambridge, Mass.). 2023;29(1):143
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IBD is characterised by chronic inflammation of the gastrointestinal tract with periodic inactive (quiescent disease) and periodic active inflammation. Chronic fatigue is regarded as elevated fatigue levels with duration of more than 6 months. Malnutrition in patients with IBD is well known and this study assessed changes in B-vitamins and their related metabolites directly after high dose oral thiamine, vitamin B1. 40 adult patients with quiescent IBD and chronic fatigue were randomised compared to a control group of 20 patients without fatigue. In total, 52 females and 8 men took part in the trial. Half of the patients had Crohn’s disease and half had ulcerative colitis. Blood samples were taken and patients answered questionnaires regarding fatigue at each study visit. The researchers found low levels of Flavin mononucleotide (FMN), a biomolecule produced from riboflavin (vitamin B2) in patients with chronic fatigue in comparison to patients without fatigue. The researchers also observed that fatigued IBD patients had a less diverse microbiome with reduced numbers of butyrate-producing bacterial species compared to non-fatigued patients, highlighting the importance of vitamin B1 for the growth of gut bacteria. The oral dose of vitamin B1 administered is unclear and other factors influencing fatigue such as diet, sleep and physical activity were not investigated. The researchers conclude the mechanisms of B-vitamins in IBD in relation to fatigue does require further exploration along with assessing vitamin B2’s effect on IBD fatigue.
Abstract
BACKGROUND High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue. METHODS Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab. RESULTS Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01). CONCLUSION FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1.
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Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.
Lai, H, Li, Y, He, Y, Chen, F, Mi, B, Li, J, Xie, J, Ma, G, Yang, J, Xu, K, et al
Gut microbes. 2023;15(1):2197837
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Functional constipation is characterised by continuously difficult, incomplete, or infrequent defecation, without an organic origin. Effective intervention strategies are required to relieve the functional constipation difficulties, particularly in rapidly aging populations, such as Chinese populations. The aim of this study was to evaluate the effectiveness of three dietary fibre formulas (polydextrose, psyllium husk, and wheat bran + psyllium husk) and one probiotic supplement on the improvement of constipation symptoms among Chinese adults with functional constipation. This study was a double-blinded randomised placebo-controlled trial which enrolled 250 participants who were randomly assigned to one of the five groups. Results showed: - that daily supplement of three prebiotic formulas with dietary fibres, or a probiotic formula effectively relieved hard stool in functional constipation patients after 4 weeks intervention. - the capacity of gut microbial genera in shaping the intervention responsiveness in the improvement of bowel movement frequency, Bristol stool scale score, and degree of defecation straining. Authors conclude that the pre or probiotic interventions may modulate gut microbiota, associated with intestinal health.
Abstract
Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884. What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber – gut microbiota (Anaerostipes)—constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.
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Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism.
Zhu, R, Fang, Y, Li, H, Liu, Y, Wei, J, Zhang, S, Wang, L, Fan, R, Wang, L, Li, S, et al
Frontiers in immunology. 2023;14:1158137
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Test anxiety, characterised by feelings of failure, tension, and worrying when an individual faces a vital test for promoting, occurs prevalently among college students. Lactobacillus plantarum, has become increasingly popular in reducing the severity of anxiety and depression in stressed animal models. The main aim of this study was to evaluate the psychological effects of Lactobacillus plantarum JYLP-326 (JYLP-326) on exam stress-induced behaviours like anxiety, depression, and insomnia. This study enrolled 60 anxious and 30 un-anxious undergraduates preparing for the approaching exams. Out of the 60 anxious participants, 30 were selected randomly to receive the probiotic product and the other 30 received a placebo product. The 30 un-anxious students were assigned as the healthy control group. Results demonstrated that the intervention of JYLP-326 is effective in alleviating exam stress-induced symptoms in college students. Furthermore, it also protected against exam stress-induced dysbiosis of the gut microbiota and the disturbances of faecal metabolomic. Authors conclude that the changed gut microbiota genera and faecal metabolites were closely associated with stress-related symptoms like anxiety/depression and insomnia, indicating that they might be regarded as biomarkers for diagnosing and treating stress and anxiety disorders.
Abstract
INTRODUCTION Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of Lactobacillus plantarum JYLP-326 on test anxious college students. METHODS Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students' mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism. RESULTS The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of Bacteroides and Roseburia at the genus level was observed in the placebo group, and the relative abundance of Prevotella and Bifidobacterium decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms. CONCLUSION The results indicate that the intervention of L. plantarum JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.