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Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial.
Tierney, BT, Versalovic, J, Fasano, A, Petrosino, JF, Chumpitazi, BP, Mayer, EA, Boetes, J, Smits, G, Parkar, SG, Voreades, N, et al
Pediatric research. 2023;93(7):2005-2013
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The composition of the human gut microbiome has been identified as playing a role in regulating bowel movements in children. This includes functional constipation, which is characterised by infrequent bowel movements and associated phenotypes such as stool consistency, pain when defecating and bloating. The aim of this study was to determine the impact of a nine-strain (eight species) synbiotic (a prebiotic and defined microbial consortium) formulation (with the prebiotic comprising mixed-chain length oligosaccharides) on ameliorating constipation. This study was a multicentre, randomised, double-blind, and placebo-controlled with two parallel arms. Ninety-one healthy male/female subjects were recruited and randomly assigned to one of the two arms; treatment or placebo group. Results showed that: - compared to placebo, synbiotic use increased weekly bowel movements (WBMs) in constipated children. - there was an increased abundance of the administered probiotic species (bifidobacteria) in the treatment arm. - baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention. Authors conclude that a synbiotic formulation may increase weekly WBMs in children who have low-frequency WBMs.
Abstract
BACKGROUND Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children. METHODS Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n = 31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo. RESULTS Treatment increased (p < 0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p = 0.00074). CONCLUSIONS These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children. IMPACT Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.
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High-fiber diet ameliorates gut microbiota, serum metabolism and emotional mood in type 2 diabetes patients.
Chen, L, Liu, B, Ren, L, Du, H, Fei, C, Qian, C, Li, B, Zhang, R, Liu, H, Li, Z, et al
Frontiers in cellular and infection microbiology. 2023;13:1069954
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Accumulating studies have demonstrated that there are strong correlations between type 2 diabetes mellitus (T2DM) and gut microbiota. A nutritious diet composed of an adequate level of dietary fibres could provide enough carbohydrates for the gut microbiota to ferment, and the microbial metabolites could provide energy supply and regulate the immune function of the host. The aim of this study was to analyse the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fibre diet. This study was a randomised, open-label, parallel-group clinical trial in T2DM patients with a 4-week treatment period. Seventeen patients clinically diagnosed with T2DM enrolled in the clinical trial and were randomly assigned into two groups: the control group (n = 8) or the intervention group (n = 9). Results showed that the high-fibre diet (compared to the control group): - improved glucose homeostasis and lipid metabolism of participants with T2DM; - decreased serum levels of inflammatory chemokines in participants with T2DM; - alleviated depression and anxiety symptoms, particularly by the uptake of more diverse carbohydrates in the diet in participants with T2DM; - enhanced the diversity of gut microbiota in the treatment group. Authors conclude that the dietary source of fibre demonstrated protective impacts on the gut ecosystem, and the alteration of the gut microbiota composition improved the glucose homeostasis in patients with T2DM.
Abstract
Previous studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) often had the problems of fecal microbiota dysbiosis, and were usually accompanied with psychiatric comorbidities (such as depression and anxiety). Here, we conducted a randomized clinical study to analyze the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fiber diet. The glucose homeostasis of participants with T2DM was improved by the high-fiber diet, and the serum metabolome, systemic inflammation and psychiatric comorbidities were also altered. The increased abundances of Lactobacillus, Bifidobacterium and Akkermansias revealed that the proportions of beneficial gut microbes were enriched by the high-fiber diet, while the abundances of Desulfovibrio, Klebsiella and other opportunistic pathogens were decreased. Therefore, the current study demonstrated that the intestinal microbiota alterations which were influenced by the high-fiber diet could improve the serum metabolism and emotional mood of patients with T2DM.
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Effects of Gut Microbiome Modulation on Reducing Adverse Health Outcomes among Elderly and Diabetes Patients during the COVID-19 Pandemic: A Randomised, Double-Blind, Placebo-Controlled Trial (IMPACT Study).
Wong, MCS, Zhang, L, Ching, JYL, Mak, JWY, Huang, J, Wang, S, Mok, CKP, Wong, A, Chiu, OL, Fung, YT, et al
Nutrients. 2023;15(8)
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Worldwide, the coronavirus disease 2019 (COVID-19) pandemic has posed a substantial challenge in terms of its induced morbidity and mortality to the general population. Patients with diabetes and elderly individuals are particularly vulnerable during the pandemic. The aim of this study was to assess the efficacy of a novel microbiome immunity formula (SIM01) in reducing adverse health outcomes in the elderly and patients with type two diabetes mellitus during the COVID-19 pandemic. This study was a double-blind, randomised, parallel-arm, placebo-controlled trial. Participants were randomly assigned to receive a microbiome immunity formula (SIM01) or placebo in a 1:1 ratio for three months. Results showed that SIM01, could reduce adverse health outcomes, improve quality of life, and restore gut dysbiosis among elderly subjects and patients with type two diabetes during the COVID-19 pandemic. In fact, SIM01 not only replenished Bifidobacteria but also favoured the coexistence of other beneficial species. Authors conclude that their findings provide significant societal implications for strategies that could protect these vulnerable individuals during the COVID-19 pandemic.
Abstract
Gut microbiota is believed to be a major determinant of health outcomes. We hypothesised that a novel oral microbiome formula (SIM01) can reduce the risk of adverse health outcomes in at-risk subjects during the coronavirus disease 2019 (COVID-19) pandemic. In this single-centre, double-blind, randomised, placebo-controlled trial, we recruited subjects aged ≥65 years or with type two diabetes mellitus. Eligible subjects were randomised in a 1:1 ratio to receive three months of SIM01 or placebo (vitamin C) within one week of the first COVID-19 vaccine dose. Both the researchers and participants were blinded to the groups allocated. The rate of adverse health outcomes was significantly lower in the SIM01 group than the placebo at one month (6 [2.9%] vs. 25 [12.6], p < 0.001) and three months (0 vs. 5 [3.1%], p = 0.025). At three months, more subjects who received SIM01 than the placebo reported better sleep quality (53 [41.4%] vs. 22 [19.3%], p < 0.001), improved skin condition (18 [14.1%] vs. 8 [7.0%], p = 0.043), and better mood (27 [21.2%] vs. 13 [11.4%], p = 0.043). Subjects who received SIM01 showed a significant increase in beneficial Bifidobacteria and butyrate-producing bacteria in faecal samples and strengthened the microbial ecology network. SIM01 reduced adverse health outcomes and restored gut dysbiosis in elderly and diabetes patients during the COVID-19 pandemic.
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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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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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REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients.
Bishop, CW, Ashfaq, A, Melnick, JZ, Vazquez-Escarpanter, E, Fialkow, JA, Strugnell, SA, Choe, J, Kalantar-Zadeh, K, Federman, NC, Ng, D, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2023;107:111899
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Literature shows that vitamin D repletion may reduce the risk for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigate severity of coronavirus disease (COVID-19), and accelerate recovery. Sufficient serum level of 25-hydroxyvitamin D (25D) is postulated to potentiate COVID-19 vaccine effectiveness, boost innate and control adaptive immunity, and reduce post-infection cytokine storm and lung injury. The aim of this study was to evaluate the safety and efficacy of extended-release calcifediol capsules to treat symptomatic patients infected with SARS-CoV-2. This study is a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial titled REsCue. One hundred seventy-one symptomatic COVID-19 outpatients participants were enrolled. Patients were randomised (1:1) to 4 weeks of treatment with extended-release calcifediol (30 mcg/capsule) or matching placebo and a 2-week follow-up. Results show that extended-release calcifediol treatment was effective in increasing serum 25D levels to ≥50 ng/mL, which may have yielded significantly shorter resolution times for three aggregated respiratory symptoms (trouble breathing, chest congestion, and dry or hacking cough) commonly observed in patients with mild to moderate COVID-19. Authors conclude that the positive findings from this study warrant confirmation in additional larger studies.
Abstract
OBJECTIVES This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19. METHODS COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). RESULTS In all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. CONCLUSION ERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.
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Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants.
Samara, J, Moossavi, S, Alshaikh, B, Ortega, VA, Pettersen, VK, Ferdous, T, Hoops, SL, Soraisham, A, Vayalumkal, J, Dersch-Mills, D, et al
Cell host & microbe. 2022;30(5):696-711.e5
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Preterm infants display a disrupted and potentially pathogenic gut microbiome compared to infants born at full term. They are also more likely to be born by caesarean section, receive antibiotics and remain in hospital for an extended period, all which can contribute to gut microbiota disruptions. Probiotics are increasingly being given to preterm infants to counteract the disruptions; however, their effects are under researched in this cohort of individuals. This randomised control trial of 57 extremely premature infants aimed to determine the effects of a probiotic supplement on gut microbiota composition and their effects on gut immunity. The results showed that Bifidobacterium strains could colonise the premature infant gut but not Lactabacillus rhamnosus. Probiotics also accelerated the maturation of the gut microbiome in premature infants and Bifidobacterium were responsible for this resulting in an anti-inflammatory effect in the gut. It was concluded that probiotic supplementation with the right microbes can act to mature the gut microbiome of preterm infants resulting in its restoration and associated health benefits. This study could be used by healthcare professionals to understand that preterm infants may have a disordered gut microbiota, but a healthy community can be restored through using a probiotic containing Bifidobacterium.
Abstract
Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bifidobacterium species autochthonous to the infant gut and one Lacticaseibacillus strain on the compositional and functional trajectory of microbiome. Daily administration of the mixture accelerated the transition into a mature, term-like microbiome with higher stability and species interconnectivity. Besides infant age, Bifidobacterium strains and stool metabolites were the best predictors of microbiome maturation, and structural equation modeling confirmed probiotics as a major determinant for the trajectory of microbiome assembly. Bifidobacterium-driven microbiome maturation was also linked to an anti-inflammatory intestinal immune milieu. This demonstrates that Bifidobacterium strains are ecosystem engineers that lead to an acceleration of microbiome maturation and immunological consequences in extremely premature infants.
