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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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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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Interactions between Mediterranean Diet Supplemented with Dairy Foods and the Gut Microbiota Influence Cardiovascular Health in an Australian Population.
Choo, JM, Murphy, KJ, Wade, AT, Wang, Y, Bracci, EL, Davis, CR, Dyer, KA, Woodman, RJ, Hodgson, JM, Rogers, GB
Nutrients. 2023;15(16)
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Diet is a fundamental determinant of metabolic health and immune regulation. Long-term dietary patterns also play an important role in shaping the intestinal commensal microbiota. The aim of this study was to explore the effects of an-8 week Mediterranean Diet enriched with dairy foods on the gut microbiome of Australian adults at risk of cardiovascular disease. This study was a randomised controlled trial with a 2 × 2 cross-over design. Participants followed a Mediterranean diet with 3–4 daily serves of dairy foods of 1000–1300mg per day (MedDairy) or low-fat diet (LFD) diet intervention for 8 weeks, separated by an 8-week washout phase where participants returned to their habitual diet. Participants (n= 43) were randomly assigned to their first dietary phase. Results showed that compared to the LFD (control), the MedDairy diet did not result in broad changes to the gut microbiota but significantly altered the relative abundance of selected bacterial taxa. Furthermore, microbial changes, including an increase in Butyricicoccus, were inversely correlated with changes in systolic blood pressure. Authors conclude that an 8-week MedDiet supplemented with dairy foods results in relative abundance changes in bacterial taxa.
Abstract
The impact of a Mediterranean diet on the intestinal microbiome has been linked to its health benefits. We aim to evaluate the effects of a Mediterranean diet supplemented with dairy foods on the gut microbiome in Australians at risk of cardiovascular disease. In a randomised controlled cross-over study, 34 adults with a systolic blood pressure ≥120 mmHg and with risk factors for cardiovascular disease were randomly allocated to a Mediterranean diet with 3-4 daily serves of dairy foods (Australian recommended daily intake (RDI) of 1000-1300 mg per day (MedDairy)) or a low-fat (LFD) control diet. Between each 8-week diet, participants underwent an 8-week washout period. Microbiota characteristics of stool samples collected at the start and end of each diet period were determined by 16S rRNA amplicon sequencing. MedDairy-associated effects on bacterial relative abundance were correlated with clinical, anthropometric, and cognitive outcomes. No change in the overall faecal microbial structure or composition was observed with either diet (p > 0.05). The MedDairy diet was associated with changes in the relative abundance of several bacterial taxa, including an increase in Butyricicoccus and a decrease in Colinsella and Veillonella (p < 0.05). Increases in Butyricicoccus relative abundance over 8 weeks were inversely correlated with lower systolic blood pressure (r = -0.38, p = 0.026) and positively correlated with changes in fasting glucose levels (r = 0.39, p = 0.019), specifically for the MedDairy group. No significant associations were observed between the altered taxa and anthropometric or cognitive measures (p > 0.05). Compared to a low-fat control diet, the MedDairy diet resulted in changes in the abundance of specific gut bacteria, which were associated with clinical outcomes in adults at risk of CVD.
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The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece-A Randomized, Double-Blind, Placebo-Controlled Study.
Zikou, E, Dovrolis, N, Dimosthenopoulos, C, Gazouli, M, Makrilakis, K
Nutrients. 2023;15(21)
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Type 2 diabetes is a multifaceted disease caused by both genetic and environmental factors such as excessive energy intake and lack of exercise. The gut microbiome has been shown to contribute to many different diseases including diabetes through its effects on the immune system, appetite, and fat storage. Probiotics are living organisms that have health benefits to humans and they have been studied for their effects on individuals with type 2 diabetes. However, the studies that have been performed have shown inconsistent results due to poorly designed trials. This randomised control trial aimed to determine the effects of a probiotic supplement containing Lactobacillus, Bifidobacterium, and Saccharomyces species on measures of blood sugar control over a period of 6 months. The results showed that compared to controls, there were significant reductions in measures of blood sugar and total cholesterol. Interestingly the probiotics did not change the diversity of the subjects gut microbiome but did alter their function noting changes in enzymes and metabolites involved in diabetes. It was concluded that over a 6-month period, the supplementation of probiotics containing Lactobacillus, Bifidobacterium, and Saccharomyces was of benefit to blood sugar balance and cholesterol levels. This study could be used by healthcare professionals to recommend a specific probiotic to individuals with type 2 diabetes.
Abstract
The role of probiotic supplementation in type 2 diabetes (T2D) treatment is controversial. The present study aimed to assess the effects of a multi-strain probiotic supplement (LactoLevureR (containing Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii)) over 6 months, primarily on glycemic control as well as on lipid levels and alterations in the gut microbiome, among individuals with T2D residing in Greece. A total of 91 adults with T2D (mean age [±SD] 65.12 ± 10.92 years, 62.6% males) were randomized to receive the probiotic supplement or a matching placebo capsule, once daily, for 6 months. Blood chemistries and anthropometric parameters were conducted every 3 months, and stool samples were collected at baseline and at 6 months. Significant reductions in HbA1c, fasting blood glucose, and total cholesterol were observed in participants treated with the probiotic supplement (n = 46) compared to the controls (n = 45), even after adjustment for a greater decrease in adiposity (waist circumference). Although there were no statistically significant differences in the diversity of the gut microbiome (α and β diversity), the administration of probiotics did influence several genera, metabolites, and key enzymes associated with diabetes. Overall, the administration of the multi-strain probiotic LactoLevureR over a 6-month period in individuals with T2D was well-tolerated and had a positive impact on metabolic parameters, alongside improvements in indices of adiposity.
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Effect of synbiotic supplementation on immune parameters and gut microbiota in healthy adults: a double-blind randomized controlled trial.
Li, X, Hu, S, Yin, J, Peng, X, King, L, Li, L, Xu, Z, Zhou, L, Peng, Z, Ze, X, et al
Gut microbes. 2023;15(2):2247025
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The gut microbiota is involved in regulating immunity and synbiotics, that is combinations of pro- and prebiotics, may therefore modulate immunity via the gut microbiota. The aim of this randomised, double-blind, placebo-controlled trial was to evaluate the immune-modulatory effects of a synbiotic supplement (containing Bifidobacterium lactis HN019, Lactobacillus rhamnosus HN001 and fructo-oligosaccharide) in healthy adults. Outcome measures included C-reactive protein (CRP, an inflammatory marker), various pro- and anti-inflammatory cytokines, stool and salivary secretory IgA (sIgA), leukocytes, microbial stool analysis and occurrence, duration, and severity of upper respiratory tract infections (URTI). Compared to the control group, a significant reduction in the inflammatory markers CRP and interferon-gamma and an increase in the anti-inflammatory interleukin-10 and stool sIgA were observed in the supplementation group. There were no differences in types of leukocytes or URTIs between groups. Significant favourable changes in microbiome analysis were observed in the supplemented group which correlated with the observed improvements in inflammatory markers. These changes were dependent on the baseline composition of the microbiome. No adverse events were reported. The authors conclude that the data show that synbiotics are of benefit to healthy adults and support the concept of personalised supplementation.
Abstract
Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.
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Effect of Lacticaseibacillus paracasei N1115 on Immunomodulatory and Gut Microbial Composition in Young Children: A Randomized, Placebo-Controlled Study.
Li, P, Ren, Z, Zhou, J, Zhao, A, Wang, S, Xun, Y, Jiang, H, Wang, P, Yuan, Q, Zhang, Y
Nutrients. 2023;15(8)
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Cesarean section (C-section) is one of the most common obstetrical procedures, and China is among the countries with the highest C-section rates in the world. Lactobacillus is one of the well-known and most studied probiotics and has a broad distribution in the human oral cavity, genitourinary tract, gastrointestinal tract, and milk. The aim of this study was to investigate the efficacy of Lp N1115 as a probiotic on immunomodulatory and gut microbial composition in Chinese infants and toddlers born by C-section. This study was a single-centre, randomised, triple-blind placebo-controlled trial. Healthy infants born by C-section were recruited at the age of 6–24 months and divided into two age groups: 6–12 months and 13–24 months. Infants and toddlers were randomly assigned to either the experimental group (Lp N1115 group) or the placebo-control group. Results showed that Lp N1115 can help maintain the intestinal pH of infants aged 6–24 months after C-section, improve immune function, and promote the proliferation of Lactobacillus. Furthermore, Lp N1115 could increase faecal secreted immunoglobulin A levels and, to some extent, reduce cortisol levels in infants and children. Authors conclude that the beneficial effects of Lp N1115 on gut development were more obvious in 6–12-month-old infants.
Abstract
Lactobacillus paracasei N1115 (Lp N1115) was isolated from fermented milk products. The administration of Lp N1115 is safe and well tolerated in Chinese children, but its effectiveness among young Chinese children is still unclear. To investigate the efficacy of Lp N1115 as a probiotic to enhance gut development in Chinese infants and toddlers born by cesarean section, 109 healthy and cesarean-delivered infants aged 6-24 months were recruited for a 12-week randomized, placebo-controlled trial, with 101 finally completing the study. Saliva and stool samples were collected and detected at weeks 0, 4, 8, and 12 of the intervention. Statistical analyses were performed by using a per-protocol (PP) approach. After 12 weeks of intervention, the fecal pH in the control group increased (p = 0.003), while the fecal pH in the experimental group did not change. Salivary cortisol decreased from baseline in the experimental group (p = 0.023), while the control group showed little change. In addition, Lp N1115 increased the fecal sIgA content of infants aged 6-12 months (p = 0.044) but had no obvious effect on fecal calprotectin and saliva sIgA. At week 4, the increase in Lactobacillus relative to baseline was higher in the experimental group than in the control group (p = 0.019). Further analysis showed a trend toward a higher detection rate of Lactobacillus in the experimental group than in the control group (p = 0.039). In conclusion, Lp N1115 was able to enhance the content of Lactobacillus and maintain fecal pH levels. Its beneficial effects on gut development were more obvious in 6-12-month-old infants.
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The Effects of Black Tea Consumption on Intestinal Microflora-A Randomized Single-Blind Parallel-Group, Placebo-Controlled Study.
Tomioka, R, Tanaka, Y, Suzuki, M, Ebihara, S
Journal of nutritional science and vitaminology. 2023;69(5):326-339
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Tea from the leaves of the tea plant (Camelia sinensis) is consumed around the world. Tea has many health benefits, and in part, this is due to its rich content in compounds classed as polyphenols. Through the fermentation process, black tea is particularly high in polyphenols. Previous studies around respiratory infections indicated that regular consumption of black tea appeared to improve immune defence mechanisms that protect mucous membranes, called mucosal immunity. As this mucosal immunity is closely influenced by gut bacteria, the authors speculated whether the previously seen impact of improved mucosal immunity is related to the ability of black tea to also modulate bacteria in the gut. A previously run randomised single-blinded, placebo-controlled trial with 72 Japanese participants who consumed three cups of black tea (2g) or a placebo of barley tea for 12 weeks provided the data for this study. Data gathered included gut flora analysis, short-chain fatty acids (SCFAs) levels - fats that play a role in maintaining gut health, and saliva IgA (SIgA) concentrations - which are antibodies made in the lymph tissue of the gut. The results showed that black tea consumption led to a significant increase in the abundance of Prevotella bacteria, which mediate SCFA production and are involved in normalising immune function. Furthermore, tea increased butyrate-producing bacteria. Butyrate is associated with improved barrier function of the gut walls but also helps to manage pathogens and immune responses. Black tea consumption also increased salivary SIgA concentration - a type of antibody on the mucous membranes that prevents pathogens from entering the body -, and a decrease in stool acetic acid concentration, which may be due to the increase in butyrate-producing bacteria which use acetic acid to make butyrate. Notably, participants with low salivary SIgA levels at the start had a more pronounced positive change in total bacteria, after consuming black tea compared to the placebo group. The authors concluded that regular consumption of black tea may help to improve mucosal immunity by increasing the abundance of beneficial bacteria in the gut.
Abstract
We previously reported that black tea consumption for 12 wk reduced the risk of acute upper respiratory tract inflammation, and improved secretory capacity in individuals with low salivary SIgA levels (Tanaka Y et al. 2021. Jpn Pharmacol Ther 49: 273-288). These results suggested that habitual black tea consumption improves mucosal immunity. Therefore, in this study we evaluated the effect of black tea intake on gut microbiota, which is known to be involved in mucosal immunity, by analyzing the bacterial flora and the short-chain fatty acids (SCFAs) concentration of feces collected during the above clinical study. The clinical design was a randomized, single-blind, parallel-group, placebo-controlled study with 72 healthy Japanese adult males and females, who consumed three cups of black tea (Black Tea Polymerized Polyphenols 76.2 mg per day) or placebo per day for 12 wk. In all subjects intake of black tea significantly increased abundance of Prevotella and decreased fecal acetic acid concentration. Particularly in the subjects with low salivary SIgA levels, the change over time of total bacteria, Prevotella, and butyrate-producing bacteria, which are involved in normalizing immune function, were higher in the black tea group than in the placebo group. In subjects with low abundance of Flavonifractor plautii a butyrate-producing bacteria, black tea consumption significantly increased salivary SIgA concentration and the absolute number of Flavonifractor plautii. In conclusion, our results suggest that improvement of mucosal immunity via an increase in butyrate-producing bacteria in the gut may partly contribute to the suppressive effect of black tea consumption on acute upper respiratory tract inflammation observed in our previous report.
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Association of Vitamin D Level and Maternal Gut Microbiome during Pregnancy: Findings from a Randomized Controlled Trial of Antenatal Vitamin D Supplementation.
Aparicio, A, Gold, DR, Weiss, ST, Litonjua, AA, Lee-Sarwar, K, Liu, YY
Nutrients. 2023;15(9)
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Changes in the gut bacteria during pregnancy and a lack of vitamin D can have negative health consequences for both mother and child. Vitamin D has important functions in the human body and is key in regulating immune and inflammatory responses. Evidence suggests that vitamin D helps to maintain gut wall integrity and regulate inflammatory mechanisms in response to bacteria. Gut bacteria themselves have immune regulatory functions, and unfavourable disruptions in the composition of the bacteria are associated with chronic inflammatory diseases. Evidence shows gut bacteria composition is influenced by Vitamin D. During pregnancy, a substantial alteration in gut bacteria composition occurs and as pregnancy advances, there's typically an increase in bacteria linked to inflammation. This study analysed the data from the Vitamin D Antenatal Asthma Reduction Trial (VDAART, 2014), a randomised placebo controlled trial which gathered information on the impact of vitamin D on various markers as well as gut microbiome composition in pregnant women. For the study all participants took a daily multivitamin with 400 IU Vitamin D during the third trimester of pregnancy, and were given either an additional 4000IU of Vitamin D or a placebo. Results were drawn from 114 participants and their baseline vitamin D levels in early pregnancy, its changes over the trial period, as well as gut bacteria composition. The vitamin D levels at the start aligned with expected outcomes and was strongly linked to race, income, and education level. The baseline vitamin D level in early pregnancy also showed a connection to certain gut microbiome composition. However, these bacterial constellations remained robust and did not show any changes in response to Vitamin D supplementation throughout pregnancy. During the trial, most participant's vitamin D levels increased, especially those in the 4400 IU treatment group. Interestingly, women whose vitamin D levels did not increase much throughout the trial displayed a higher abundance of a bacteria called Desulfovibrio. Desulfovibrio is associated with an increased incidence of respiratory and inflammatory bowel diseases and the authors suggested that increasing vitamin D during pregnancy might help prevent the growth of more unfavourable bacteria like Desulfovibrio. Further long-term research is needed to confirm this idea.
Abstract
Shifts in the maternal gut microbiome and vitamin D deficiency during pregnancy have been associated, separately, with health problems for both the mother and the child. Yet, they have rarely been studied simultaneously. Here, we analyzed the gut microbiome (from stool samples obtained in late pregnancy) and vitamin D level (from blood samples obtained both in early and late pregnancy) data of pregnant women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized controlled trial of vitamin D supplementation during pregnancy, to investigate the association of vitamin D status on the pregnant women's microbiome. To find associations, we ran linear regressions on alpha diversity measures, PERMANOVA tests on beta diversity distances, and used the ANCOM-BC and Maaslin2 algorithms to find differentially abundant taxa. Analyses were deemed significant using a cut-off p-value of 0.05. We found that gut microbiome composition is associated with the vitamin D level in early pregnancy (baseline), the maternal gut microbiome does not show a shift in response to vitamin D supplementation during pregnancy, and that the genus Desulfovibrio is enriched in women without a substantial increase in vitamin D level between the first and the third trimesters of pregnancy. We conclude that increasing the vitamin D level during pregnancy could be protective against the growth of sulfate-reducing bacteria such as Desulfovibrio, which has been associated with chronic intestinal inflammatory disorders. More in-depth investigations are needed to confirm this hypothesis.
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Effects of a low FODMAP diet on gut microbiota in individuals with treated coeliac disease having persistent gastrointestinal symptoms - a randomised controlled trial.
Herfindal, AM, van Megen, F, Gilde, MKO, Valeur, J, Rudi, K, Skodje, GI, Lundin, KEA, Henriksen, C, Bøhn, SK
The British journal of nutrition. 2023;130(12):2061-2075
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Coeliac disease (CeD) is a common immune-mediated disease where intolerance to gluten can lead to severe health problems with a wide range of gastrointestinal (GI) and extra-intestinal symptoms. Research shows that a diet low in fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) helps to reduce GI symptoms in irritable-bowel syndrome and gluten-free diet treated CeD. The aim of this study was to investigate whether a low FODMAP diet (LFD) in this patient group affects (i) the faecal microbiota, (ii) the concentrations of faecal short-chain fatty acids (SCFA) and (iii) the concentrations of faecal human neutrophil gelatinase-associated lipocalin (a biomarker of gut inflammation). This study is part of a clinical trial which followed a nonblinded, parallel randomised design. The participants were randomised to either an LFD group or a control group. Results showed that after four weeks, certain differences in gut microbiota were detected between the control and LFD group. The SCFA results indicated that the LFD resulted in lower concentrations of propionic and valeric acid in participants with initially high concentrations. Biomarker of gut inflammation was, however, unaffected by the LFD. Authors conclude that the LFD led to changes in overall community structure of the faecal microbiota, with a possible unfavourable low faecal abundance of Anaerostipes, and low concentrations of the faecal SCFA propionic and valeric acid in participants with high concentrations of these acids at baseline.
Abstract
Individuals with coeliac disease (CeD) often experience gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). While we recently showed that a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAP) successfully provided symptom relief in GFD-treated CeD patients, there have been concerns that the low FODMAP diet (LFD) could adversely affect the gut microbiota. Our main objective was therefore to investigate whether the LFD affects the faecal microbiota and related variables of gut health. In a randomised controlled trial GFD-treated CeD adults, having persistent gastrointestinal symptoms, were randomised to either consume a combined LFD and GFD (n 39) for 4 weeks or continue with GFD (controls, n 36). Compared with the control group, the LFD group displayed greater changes in the overall faecal microbiota profile (16S rRNA gene sequencing) from baseline to follow-up (within-subject β-diversity, P < 0·001), characterised by lower and higher follow-up abundances (%) of genus Anaerostipes (Pgroup < 0·001) and class Erysipelotrichia (Pgroup = 0·02), respectively. Compared with the control group, the LFD led to lower follow-up concentrations of faecal propionic and valeric acid (GC-FID) in participants with high concentrations at baseline (Pinteraction ≤ 0·009). No differences were found in faecal bacterial α-diversity (Pgroup ≥ 0·20) or in faecal neutrophil gelatinase-associated lipocalin (ELISA), a biomarker of gut integrity and inflammation (Pgroup = 0·74), between the groups at follow-up. The modest effects of the LFD on the gut microbiota and related variables in the CeD patients of the present study are encouraging given the beneficial effects of the LFD strategy to treat functional GI symptoms (Registered at clinicaltrials.gov as NCT03678935).