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Collinsella aerofaciens as a predictive marker of response to probiotic treatment in non-constipated irritable bowel syndrome.
Gargari, G, Mantegazza, G, Cremon, C, Taverniti, V, Valenza, A, Barbaro, MR, Marasco, G, Duncan, R, Fiore, W, Ferrari, R, et al
Gut microbes. 2024;16(1):2298246
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Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction in which recurrent abdominal pain is associated with defecation or a change in bowel habits. Various therapeutic options for IBS target the underlying pathophysiological aspects of the condition. Unfortunately, no single approach can effectively address this disorder’s diverse manifestations simultaneously. The aim of this study was to identify markers for recognising non-constipated (NC) IBS patients that may show significant clinical improvements upon treatment with the probiotic strain Lacticaseibacillus paracasei DG (LDG). This study is based on a multicentre, randomised, double-blind, parallel-group, placebo-controlled clinical trial. A total of 63 patients were included in this study who were randomised to receive a probiotic treatment or placebo capsules for 12 weeks. Results showed that the probiotic bacterium LDG can be clinically effective in a subgroup of non-constipated IBS patients characterised by an altered faecal microbiota which resembles that observed in metabolic syndrome-associated pathologic or pre-pathologic conditions. Furthermore, a bacterium reported to contribute to pro-inflammatory immune states, was positively associated with markers of increased endothelial permeability and liver functionality Authors concluded that an analysis of the faecal microbiota focused on particular bacteria could permit the identification of NC-IBS patients who can obtain a significant clinical benefit from the probiotic treatment.
Abstract
Probiotics are exploited for adjuvant treatment in IBS, but reliable guidance for selecting the appropriate probiotic to adopt for different forms of IBS is lacking. We aimed to identify markers for recognizing non-constipated (NC) IBS patients that may show significant clinical improvements upon treatment with the probiotic strain Lacticaseibacillus paracasei DG (LDG). To this purpose, we performed a post-hoc analysis of samples collected during a multicenter, double-blind, parallel-group, placebo-controlled trial in which NC-IBS patients were randomized to receive at least 24 billion CFU LDG or placebo capsules b.i.d. for 12 weeks. The primary clinical endpoint was the composite response based on improved abdominal pain and fecal type. The fecal microbiome and serum markers of intestinal (PV1 and zonulin), liver, and kidney functions were investigated. We found that responders (R) in the probiotic arm (25%) differed from non-responders (NR) based on the abundance of 18 bacterial taxa, including the families Coriobacteriaceae, Dorea spp. and Collinsella aerofaciens, which were overrepresented in R patients. These taxa also distinguished R (but not NR) patients from healthy controls. Probiotic intervention significantly reduced the abundance of these bacteria in R, but not in NR. Analogous results emerged for C. aerofaciens from the analysis of data from a previous trial on IBS with the same probiotic. Finally, C. aerofaciens was positively correlated with the plasmalemmal vesicle associated protein-1 (PV-1) and the markers of liver function. In conclusion, LDG is effective on NC-IBS patients with NC-IBS with a greater abundance of potential pathobionts. Among these, C. aerofaciens has emerged as a potential predictor of probiotic efficacy.
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Effects of Spirulina supplementation in patients with ulcerative colitis: a double-blind, placebo-controlled randomized trial.
Moradi, S, Bagheri, R, Amirian, P, Zarpoosh, M, Cheraghloo, N, Wong, A, Zobeiri, M, Entezari, MH
BMC complementary medicine and therapies. 2024;24(1):109
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Ulcerative colitis (UC) is a form of inflammatory bowel disease, that may be caused by genetic variations in the gut microbiome, immune dysregulation, and environmental influences. Symptoms include diarrhoea, constipation, cramping, joint pain, bleeding, and anaemia. Inflammation is a direct driver of UC, which if controlled may be of benefit to the individual. Spirulina, which is a species of seaweed, has been shown to have anti-inflammatory properties and this randomised control trial aimed to determine the effects of its supplementation on 80 individuals with UC and associated health outcomes. The results showed that 8-weeks of Spirulina supplementation significantly increased antioxidant capacity compared to placebo. However, an assessment of quality of life and level of disease showed no improvements with Spirulina supplementation. It was concluded that Spirulina supplementation for 8-weeks improved antioxidant status, but it did not affect severity of disease or quality of life. This study could be used by healthcare professionals to understand that Spirulina supplementation for 8-weeks can improve inflammation. However, it would be interesting to see longer studies to determine if this would affect disease status if supplemented for a longer period of time.
Abstract
AIM: We conducted a randomized placebo-controlled trial to assess the efficacy of Spirulina (SP) supplementation on disease activity, health-related quality of life, antioxidant status, and serum pentraxin 3 (PTX-3) levels in patients with ulcerative colitis (UC). METHODS Eighty patients with UC were randomly assigned to consume either 1 g/day (two 500 mg capsules/day) of SP (n = 40) or control (n = 40) for 8 weeks. Dietary intakes, physical activity, disease activity, health-related quality of life, antioxidant status, erythrocyte sedimentation rate (ESR), and serum PTX-3 levels were assessed and compared between groups at baseline and post-intervention. RESULTS Seventy-three patients (91.3%) completed the trial. We observed increases in serum total antioxidant capacity levels in the SP supplementation group compared to the control group after 8 weeks of intervention (p ≤ 0.001). A within-group comparison indicated a trend towards a higher health-related quality of life score after 8 weeks of taking two different supplements, SP (p < 0.001) and PL (p = 0.012), respectively. However, there were no significant changes in participant's disease activity score in response to SP administration (p > 0.05). Similarly, changes in ESR and PTX-3 levels were comparable between groups post-intervention (p > 0.05). CONCLUSIONS SP improved antioxidant capacity status and health-related quality of life in patients with UC. Our findings suggest that SP supplementation may be effective as an adjuvant treatment for managing patients with UC. Larger trials with longer interventions periods are required to confirm our findings.
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Selenium Supplementation in Patients with Hashimoto Thyroiditis:A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Huwiler, VV, Maissen-Abgottspon, S, Stanga, Z, Mühlebach, S, Trepp, R, Bally, L, Bano, A
Thyroid : official journal of the American Thyroid Association. 2024
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Hashimoto Thyroiditis (HT) is a disease of the thyroid gland, which can result in insufficient production of thyroid hormone. Thyroid hormone is responsible for numerous functions within the body, such as weight regulation and energy production. Selenium is a nutrient that is used in the body to make thyroid hormones and low levels have been seen in patients with HT. Selenium supplementation has been researched previously, but inconsistent results have been shown. This systematic review and meta-analysis of 35 and 32 randomised control trials respectively, aimed to determine the effect of selenium supplementation on HT. The results showed that selenium supplementation favourably influenced thyroid hormones and oxidative stress, without affecting inflammation, but only if individuals were not receiving thyroid hormone replacement therapy. Adverse events were similar between the supplementation and control groups. It was concluded that selenium supplementation is a safe and effective therapy for individuals with HT who are not receiving hormone replacement therapy. This study could be used by healthcare professionals to recommend selenium supplementation as a way to balance thyroid hormones and alleviate the effects of HT.
Abstract
Background: Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; I2 = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; I2 = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; I2 = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; I2 = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. Conclusions: In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.
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The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.
Santo André, HC, Esteves, GP, Barreto, GHC, Longhini, F, Dolan, E, Benatti, FB
Advances in nutrition (Bethesda, Md.). 2023;14(1):115-127
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Omega 3 polyunsaturated fatty acids (n-3PUFA) are long-chain polyunsaturated fatty acids essential to human health. They play a role in cell membrane integrity, immune and inflammation regulation, cognition and neuromuscular function. As the human body cannot make these fatty acids, they need to be obtained through diet or supplementation. Regarding skeletal muscle, recent research showed that n-3PUFAs may increase the uptake of amino acids by increasing the membrane fluidity in the muscle, and by activating pathways that inhibit protein breakdown. This led to the hypothesis that n-3PUFAs may enhance muscle mass gain and strength. This systematic review sought to gather all available evidence about the impact of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. The review included 14 studies with a total of 1443 participants. The authors found that n-3PUFA supplementation had no significant effect on muscle mass or muscle function in healthy young and older adults, however, a very small but significant positive effect was noted regarding muscle strength. In the discussion section, the authors explain the challenges of their review and how these findings integrate with the current understanding and other research findings. They concluded more research is needed to get a better insight into the effects of n-3PUFA on muscle function and the variants.
Abstract
The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.
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The Influence of Nutritional Intervention in the Treatment of Hashimoto's Thyroiditis-A Systematic Review.
Osowiecka, K, Myszkowska-Ryciak, J
Nutrients. 2023;15(4)
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Hashimoto’s thyroiditis is an autoimmune disorder characterized by the presence of antibodies in the thyroid gland such as thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies. Immune-mediated inflammatory responses eventually lead to the progressive destruction of the gland and impaired thyroid function. The disease has a strong genetic disposition but is also influenced by environmental factors, including diet. Hence diet has been considered a complementary tool to manage thyroid function and disease progression by harnessing the benefits of certain nutrients and anti-inflammatory properties. This systematic review examined the effects of nutrients and dietary interventions on Hashimoto’s disease in current literature. Using antibody levels, thyroid hormone levels and body weight to measure outcomes. The review included 9 studies, all of which compared the intervention group to the control groups. The trials included looked at gluten-free, lactose-free and energy-restricted diets, with or without selected nutrients and foods supplements (ie. Nigella sativa, iodine). The intervention duration ranged from 3 weeks to 12 months. Despite the small number of trials, the data from those studies included in this review showed promising results. Improvements in disease parameters were observed in diets that were energy deficient, eliminated gluten, lactose and goitrogens or added Nigella sativa. Iodine restrictions did not show any improvements. In the discussion section, the authors presented the results in the wider context and the findings from other studies. Ultimately there appears to be a wide variance in outcomes, usually ranging from beneficial to neutral. The authors contributed to such variability due to the complexity of the condition and many influencing factors. Often participants in trials have highly variable thyroid status and function, and differences in regular dietary intakes of nutrients critical to thyroid health can easily distort the results. Hence much more specific research is needed to make firmer conclusions. Whereby no clear conclusions in larger groups could be drawn, potential benefits of dietary interventions in Hashimoto's disease may be much more apparent in clinical settings with personalized approaches that account for such individual variances.
Abstract
Diet can be a complementary treatment for Hashimoto's disease by affecting thyroid function and anti-inflammatory properties. It is still unclear which dietary strategy would be the most beneficial. The aim of this systematic review is to examine all the data currently available in the literature on the effects of nutritional intervention on biochemical parameters (anti-thyroid antibody and thyroid hormones levels) and characteristic symptoms in the course of Hashimoto's thyroiditis. This systematic review was prepared based on PRISMA guidelines. Articles in PubMed and Scopus databases published up to November 2022 were searched. As a result of the selection, out of 1350 publications, 9 were included for further analysis. The nutritional interventions included the following: elimination of gluten (3 articles) or lactose (1 article), energy restriction with or without excluding selected foods (n = 2), consumption of Nigella sativa (n = 2), or dietary iodine restriction (n = 1). The intervention duration ranged from 21 days to 12 months and included individuals with various thyroid function. Of the nine studies, three studies were female only. An improvement was observed during an energy deficit and after the elimination of selected ingredients (e.g., gluten, lactose, or goitrogens), as well as after the intervention of Nigella sativa. These interventions improved antibody levels against peroxidase (anti-TPO), (thyrotropin) TSH, and free thyroxine (fT4). No improvement was seen on the iodine-restricted diet. Varied outcomes of analyzed dietary interventions may be due to the heterogeneous thyroid condition, high variability between patients, and differences in habitual intake of critical nutrients (e.g., iodine, selenium, and iron) in different populations. Therefore, there is a great need for further experimental studies to determine whether any nutritional interventions are beneficial in Hashimoto's disease.
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Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD-A Randomized Controlled Trial.
Yang, LL, Stiernborg, M, Skott, E, Xu, J, Wu, Y, Landberg, R, Arefin, S, Kublickiene, K, Millischer, V, Nilsson, IAK, et al
Nutrients. 2023;15(5)
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Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental psychiatric disorder. The core symptoms of the disorder are inattention and hyperactivity/impulsivity. The aim of this study was to explore the effects of Synbiotic 2000 on concentrations of plasma immune activity markers and short-chain fatty acids (SCFAs) in ADHD. This study is a double-blind randomised controlled trial over a period of 9-weeks. Patients (n= 248) were randomly allocated to one of the two treatments: Synbiotic 2000 or placebo. Results show that there was no statistically significant overall effect of Synbiotic 2000 compared to placebo on any analyte analysing all the paediatric and all adult participants as one group. However, age-group stratified analyses showed that plasma levels of several of the analytes were at baseline different in the children compared to in the adults. Authors conclude that Synbiotic 2000, in children with ADHD, reduces markers of intestinal and vascular inflammation, the latter in part through increasing SCFAs levels. Furthermore, they suggest that the findings warrant further studies to determine if persons with ADHD would benefit inflammation-wise from dietary intake of Synbiotic 2000 or a similar synbiotic.
Abstract
Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota-gut-brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.
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Blueberries Improve Abdominal Symptoms, Well-Being and Functioning in Patients with Functional Gastrointestinal Disorders.
Wilder-Smith, CH, Materna, A, Olesen, SS
Nutrients. 2023;15(10)
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Functional gastrointestinal disorders (FGID) are the most common cause of recurring, chronic digestive upsets. Irritable bowel syndrome (IBS) and functional dyspepsia (FD), or persistent indigestion, are the most prevalent types of those disorders. Typical symptoms include pain or discomfort in the abdomen, changes in stool patterns or bloating and may also manifest in symptoms not directly relating to the digestive tract. It remains uncertain what the exact mechanisms of those disorders are. However, scientists identified various factors involved, including immune system activation, sensitisation of the nervous system, dysregulated permeability of the gut walls, and changes in the microbiota, their composition and metabolic activity. Polyphenols are natural compounds found abundantly in plants and are most known for their antioxidant qualities. One frequently studied and rich-source of phenols is Blueberries (Vaccinium spp). Blueberries have antioxidant, anti-inflammatory, and neuroprotective properties, and are known to reverse the permeability of the gut membrane. Hence their use in the management of FGID appeared promising. This double-blind, randomized, cross-over study assessed the benefit of blueberries in 43 people with IBS or FD, between 18–60 years of age. The candidates were given 30g freeze-dried blueberries, the equivalent of 180g of fresh blueberries, or a sugar-based placebo of similar calorific value for 6-weeks each. When receiving the blueberries, greater symptom relief was observed when compared to the placebo group. Blueberry intake also positively reflected in experienced improvement in quality of life. No notable differences were observed between groups in stool patterns and fructose digestion. Blueberries and their beneficial compounds such as polyphenols and fiber appear to have a wide range of benefits that can help manage some of the FGID-associated symptoms. Further studies are needed to understand why, despite some notable benefits, some of the other GI markers remained unaffected. As blueberries are generally well tolerated, they can be a simple and helpful food intervention to complement other FGID management strategies.
Abstract
Blueberries beneficially modulate physiologic mechanisms relevant to the pathogenesis of functional gastrointestinal disorders (FGID). Forty-three patients with FGID received freeze-dried blueberries (equivalent to 180 g fresh blueberries) or sugar and energy-matched placebo in a double-blind, randomized, cross-over study. After 6 weeks of treatment, the differences in Gastrointestinal Clinical Rating Scale (GSRS) scores and abdominal symptom relief were compared as primary outcome measures. The quality of life and life functioning ratings (OQ45.2 questionnaire), Bristol stool scales, and fructose breath test results constituted secondary outcome measures. Blueberry treatment resulted in more patients with relevant abdominal symptom relief compared to placebo (53% vs. 30%, p = 0.03). Total and pain GSRS scores improved insignificantly (mean treatment differences [95% CI]: -3.4 [-7.4 to 0.6] (p = 0.09) and -1.0 [-2.2 to 0.1] (p = 0.08), respectively). OQ45.2 scores improved during blueberry treatment compared to placebo (treatment difference -3.2 [95% CI: -5.6 to -0], p = 0.01). Treatment effect differences for the further measures did not reach statistical significance. Blueberries relieved abdominal symptoms and improved general markers of well-being, quality of life, and life functioning more than placebo in patients with FGID. Consequently, the polyphenol and fiber components of blueberries exert broad beneficial effects separate from the sugars present in both treatments.
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Efficacy of diet restriction with or without probiotic for treatment of patients with IBS-D: Phase I-II clinical trial.
Zhao, XS, Shi, LJ, Ning, BL, Zhao, ZM, Li, XX, Zhu, MH, Zhang, YB, Fu, J
Immunity, inflammation and disease. 2023;11(5):e857
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Irritable bowel syndrome (IBS) is a functional intestinal disorder that can significantly affect quality of life. IBS patients suffer from intermittent abdominal pain/ discomfort, altered bowel habits, and abdominal bloating/distension. The aim of this study was to assess the effects of dietary restriction and probiotic use on IBS‐D patients. This study was a 2 × 2 factorial design, single‐centre, randomised trial. Phase 1 was a 12‐week dietary intervention, with 214 participants randomised to an IgG positive restricted diet (IgG res diet) or a control diet (cold/spicy/fried restricted). In Phase 2, 167 participants were randomised into either an IgG res diet + placebo or an IgG res diet + probiotic for 12 weeks. Symptom Severity Scale (IBS‐D‐SSS) and IgG titer were assessed at the beginning and the end of the study. Results showed that both diets reduced IBS‐D symptom severity scores and decreased immunoglobulin (IgG) antibody titer, although the IgG res diet had a greater impact. IBS symptom scores decreased with the addition of a Bifidobacterium probiotic along with dietary exclusion, however, IgG titers did not change with the probiotic compared to placebo. Authors concluded that diet restriction with appropriate and effective probiotics, provides greater symptom reductions for patients with IBS-D.
Expert Review
Conflicts of interest:
None
Take Home Message:
For individuals with IBDS-D:
- Establish IgG intolerances to foods and ensure an elimination diet remains nutritionally balanced
- Consider combining elimination diet with a Bifidobacterium supplement.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Irritable bowel syndrome (IBS) is a common functional intestinal disorder, affecting 5-20% of the population and diet is likely a major factor in its development as well as in its management. The aim of this study was to compare 3 dietary interventions and the use of a probiotic supplement in patients with IBS-diarrhoea dominant (IBS-D).
Methods
The study was conducted in 2 phases. The first was a 12-week 2 × 2 factorial design, randomised dietary intervention and included 224 patients (214 completed) with IBS-D. The diets were an Eastern/Chinese restriction diet, avoiding cold/raw, spicy and fried foods (CSF), the second avoided common allergens as determined by an IgG test (IgG diet, 14 foods tested), the third a combination of the two, whilst the control group continued their usual (Eastern/Chinese) diet.
The second phase was a 12-week randomised, double-blind, placebo-controlled trial comparing the CSF + IgG diet plus placebo with the CSF + IgG diet plus a 2 billion Bifidobacterium adolescentis supplement; this part included 202 patients of whom 169 completed the study.
The primary outcomes under observation were a reduction in IBS-D symptom severity Score (IBS-D-SSS) and IgG antibody titre (TigG).
Results
Phase 1: The IBS-D-SSS improved in all four groups from baseline (p<0.001), with the intervention groups improving significantly more than the control group (p<0.001). There was no statistically significant difference between the IgG and the IgG + CSF groups, although the authors considered there to be a synergistic effect. Statistically significant (p<0.001) reductions in TIgG were seen in all interventions, but not the control group.
Part 2: Significant (p<0.001) improvements in IBS-D-SSS were seen with both placebo and Bifidobacterium, although this was greater in the probiotic group (p<0.001). Improvements in TIgG were seen in both groups (p<0.001), with no difference between groups.
Conclusion
The authors concluded that the best intervention for patients with IBD-D is an IgG food elimination diet together with a Bifidobacterium probiotic supplement.
Clinical practice applications:
- Consider an elimination diet based on IgG testing for clients with IBS-D
- Consider combining elimination diet with a Bifidobacterium supplement. The dose used in this study was 4x 0.5 billion capsules of Bifidobacterium adolescentis
- Eliminating cold/raw, spicy and fried food could be an alternative to IgG elimination if the latter is not suitable for the client.
Considerations for future research:
- 45% and 35% of screened patients, respectively in the 2 phases of the study, were IgG negative. Screening for more potential food intolerances may extend the suitability of the approach to more patients
- Only a single strain probiotic was tested. Further research could evaluate other or combinations of Bifidobacteria strains in combination with an IgG elimination diet
- The mechanism(s) by which probiotics may affect symptoms of IBS-D are unknown. Adding stool microbiome analyses may shed further light on the effect of the intervention on the composition and function of the microbiome.
Abstract
BACKGROUND AND AIM Diet is a major contributor to irritable bowel syndrome (IBS) and is also a powerful tool for treatment of IBS. This study compared two diets and explored the effectiveness of the diets when combined with a probiotic for treatment of IBS-D patients. METHODS Phase I, patients were randomized into groups; control, cold/spicy/fried restricted diet (CSF res diet), IgG positive restricted diet (IgG res diet), and a combination both diets (CSF + IgG res diet). Phase II, patients were randomized into IgG res diet + placebo and IgG res diet + probiotic. Both interventions were 12 weeks in duration. Symptom Severity Scale (IBS-D-SSS) and IgG titer were assessed at the beginning and the end of the study. RESULTS Totals of 214 and 167 patients completed the two parts of the study, respectively. After intervention, IBS-D-SSS and TIgG grade were significantly improved compared to baseline, with results similar to the control group. In general, there were decreases in IBS-D-SSS and TIgG grade that were significantly different among the groups. There were exceptions; no differences were observed for IBS-D-SSS between the IgG res diet and CSF + IgG res diet, or TIgG grade between the CSF res diet, IgG res diet, and CSF + IgG res diet. However, the CSF res diet and IgG res diet had a synergistic effect that decreased IBS-D-SSS and TIgG titer, with a greater contribution by the IgG res diet. Therefore, we evaluated the IgG res diet with either placebo or probiotic and found that IBS-D-SSS and TIgG grade decreased from baseline. There was a significant decrease in IBS-D-SSS with the probiotic but TIgG grade was not significantly different between the IgG diet + placebo and IgG diet + probiotic diet. CONCLUSIONS Both the CSF res diet and IgG res diet improved IBS symptoms and demonstrated synergy, although the IgG res diet had a greater contribution. Further, when intolerant foods cannot be eliminated from a diet, avoiding uncooked, cold, spicy, fried, and alcoholic foods is a superior choice. The IgG res diet combined with Bifidobacteria was the best dietary choice and may function though a non-IgG pathway.
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Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet.
Wastyk, HC, Perelman, D, Topf, M, Fragiadakis, GK, Robinson, JL, Sonnenburg, JL, Gardner, CD, Sonnenburg, ED
Gut microbes. 2023;15(1):2178794
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Rates of metabolic syndrome are high throughout developed countries. Metabolic syndrome is a cluster of conditions that occur together and increase your risk for heart disease, stroke, and type 2 diabetes. Studies in animals and humans have shown that the composition of the gut microbiome may be linked to metabolic syndrome and that it is affected by diet. This randomised control trial of 39 individuals showed that the supplementation of a probiotic containing three different probiotic strains did not have a population wide effect but did influence a subset of individuals. These individuals had a different microbiome by the end of the trial and a decrease in blood pressure and blood lipids. Interestingly these individuals also had a higher dietary intake of sugar, yet a lower blood sugar level. It was concluded that the response to probiotic supplements may be dependent upon an individual’s diet. This study could be used by healthcare professionals to understand that diet may influence the success of probiotics, however more research is warranted before firm conclusions are made on the optimal diet during supplementation.
Abstract
An individual's immune and metabolic status is coupled to their microbiome. Probiotics offer a promising, safe route to influence host health, possibly via the microbiome. Here, we report an 18-week, randomized prospective study that explores the effects of a probiotic vs. placebo supplement on 39 adults with elevated parameters of metabolic syndrome. We performed longitudinal sampling of stool and blood to profile the human microbiome and immune system. While we did not see changes in metabolic syndrome markers in response to the probiotic across the entire cohort, there were significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants. Conversely, the non-responders had increased blood glucose and insulin levels over time. The responders had a distinct microbiome profile at the end of the intervention relative to the non-responders and placebo arm. Importantly, diet was a key differentiating factor between responders and non-responders. Our results show participant-specific effects of a probiotic supplement on improving parameters of metabolic syndrome and suggest that dietary factors may enhance stability and efficacy of the supplement.
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Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Deng, N, Reyes-Uribe, L, Fahrmann, JF, Thoman, WS, Munsell, MF, Dennison, JB, Murage, E, Wu, R, Hawk, ET, Thirumurthi, S, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;29(21):4361-4372
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Plain language summary
Lynch syndrome (LS) is a genetic disorder conferring a 60% lifetime risk of developing colorectal cancer (CRC). Exercise is associated with a reduction in CRC risk in the general population, potentially mediated via modulation of inflammation. The aim of this non-randomised, controlled trial was to test whether an intervention consisting of 3 x 45-minute cycling classes per week for 12 months affects inflammatory factors (prostaglandin E2, PGE2) in the colorectal mucosa and blood and whether this intervention is feasible in LS carriers. The control group received usual care with one session of exercise counselling. Of 60 patients invited to join the study, 21 (35%) agreed to take part. Of the 11 participants in the intervention group, 9 (81.2%) completed the study with an average adherence to the intervention of 51.3%, compared to 7/10 completing in the control group. VO2 peak (maximal aerobic capacity) increased significantly in the intervention group, compared to the control group over the 12 months. Patients in the intervention group also had a significant reduction in colonic and systemic PGE2 levels compared to controls following intervention. Changes in gene expression which may reflect an increased immune surveillance of the colon were also observed in the intervention group. The authors concluded that the study confirmed that exercise may modulate inflammation in the colonic mucosa in patients at high risk of CRC and that further randomised studies are necessary to confirm the potential benefits of exercise for patients with LS.
Abstract
PURPOSE Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.