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Effects of Wholegrain Compared to Refined Grain Intake on Cardiometabolic Risk Markers, Gut Microbiota, and Gastrointestinal Symptoms in Children: A Randomized Crossover Trial.
Madsen, MTB, Landberg, R, Nielsen, DS, Zhang, Y, Anneberg, OMR, Lauritzen, L, Damsgaard, CT
The American journal of clinical nutrition. 2024;119(1):18-28
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High consumption of wholegrain foods has been linked to a lower risk of cardiovascular disease (CVD) and type 2 diabetes. Some trials have shown benefits to body weight, blood lipids and glucose homeostasis but most of these studies are with adults. Cardiometabolic disease begins in childhood therefore data is needed for this age group to back up dietary recommendations in order to prevent later development of cardiometabolic disease. The aim of this randomized crossover trial was to look at the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL), cholesterol and plasma insulin, other cardiometabolic markers, body composition, the composition of the gut microbiome and gastrointestinal symptoms in children with high body mass index (BMI). 55 healthy Danish children (aged 8 – 13) took part. They ate wholegrain oats and rye (WG) or refined grain products (RG) ad libtum for 8 weeks in random order. Measurements were taken at 0, 8 and 16 weeks. Compared with RG, WG reduced LDL cholesterol as well as total:high-density lipoprotein cholesterol and triacylglycerol. WG also modulated the abundance of specific types of gut bacteria, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. This study supports the recommendation to swap refined grain for wholegrain oats and rye in children. Further studies are needed.
Abstract
BACKGROUND Wholegrain intake is associated with lower risk of cardiometabolic diseases in adults, potentially via changes in the gut microbiota. Although cardiometabolic prevention should start early, we lack evidence on the effects in children. OBJECTIVES This study investigated the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL) cholesterol and plasma insulin (coprimary outcomes), other cardiometabolic markers, body composition, gut microbiota composition and metabolites, and gastrointestinal symptoms in children with high body mass index (BMI). METHODS In a randomized crossover trial, 55 healthy Danish 8- to 13-y-olds received wholegrain oats and rye ("WG") or refined grain ("RG") products ad libitum for 8 wk in random order. At 0, 8, and 16 wk, we measured anthropometry, body composition by dual-energy absorptiometry, and blood pressure. Fasting blood and fecal samples were collected for analysis of blood lipids, glucose homeostasis markers, gut microbiota, and short-chain fatty acids. Gut symptoms and stool characteristics were determined by questionnaires. Diet was assessed by 4-d dietary records and compliance by plasma alkylresorcinols (ARs). RESULTS Fifty-two children (95%) with a BMI z-score of 1.5 ± 0.6 (mean ± standard deviation) completed the study. They consumed 108 ± 38 and 3 ± 2 g/d wholegrain in the WG and RG period, which was verified by a profound difference in ARs (P < 0.001). Compared with RG, WG reduced LDL cholesterol by 0.14 (95% confidence interval: -0.24, -0.04) mmol/L (P = 0.009) and reduced total:high-density lipoprotein cholesterol (P < 0.001) and triacylglycerol (P = 0.048) without altering body composition or other cardiometabolic markers. WG also modulated the abundance of specific bacterial taxa, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. CONCLUSION High intake of wholegrain oats and rye reduced LDL cholesterol and triacylglycerol, modulated bacterial taxa, and increased beneficial metabolites in children. This supports recommendations of exchanging refined grain with wholegrain oats and rye among children. This trial was registered at clinicaltrials.gov as NCT04430465.
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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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Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits.
Wang, H, Ma, C, Li, Y, Zhang, L, A, L, Yang, C, Zhao, F, Han, H, Shang, D, Yang, F, et al
Microbiology spectrum. 2023;11(3):e0444022
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A long-term high-fat diet will not only disrupt the balance of lipid metabolism in the body and cause metabolic disorders but also lead to chronic diseases, such as hyperlipidaemia, type 2 diabetes, hypertension, and obesity. Hyperlipidaemia is also an important contributing factor in cardiovascular disease. The aim of this study was to analyse the effects of a mixed probiotic formulation on hyperlipidaemia, with focus on changes in patients’ gut microbiota and their metabolic potential. This study was a 3-month randomised controlled intervention trial. A total of 56 hyperlipidaemic patients were recruited and randomised into either the placebo or probiotic (receiving a mixed probiotic formulation) group. Results show that the intake of the probiotic mix effectively reduced the serum levels of total cholesterol and low-density lipoprotein cholesterol, while increasing serum high-density lipoprotein cholesterol levels, in patients with hyperlipidaemia. In fact, there was a strong association between the desirable changes in patients’ lifestyle habits and lowering of these indexes. Furthermore, although insignificant changes were observed in the lipid metabolome and gut microbiota structure, some interesting fecal bacteria and blood metabolites increased significantly after Probio-X intervention. Authors conclude that their findings show that probiotic administration is a promising approach in managing hyperlipidaemia and improving public health.
Abstract
Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.
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Orally administrated Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 can restore the vaginal health of patients recovering from bacterial vaginosis.
Qi, F, Fan, S, Fang, C, Ge, L, Lyu, J, Huang, Z, Zhao, S, Zou, Y, Huang, L, Liu, X, et al
Frontiers in immunology. 2023;14:1125239
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Bacterial vaginosis (BV) is a microecological disorder caused by decreased abundance of lactobacilli and an increased abundance of anaerobic bacteria, commonly affecting the female lower genital tract. The aim of this study was to evaluate the effectiveness of oral Chinese-origin probiotic strains (L. gasseri TM13 and L. crispatus LG55), with adjuvant primary treatment in treating Chinese BV patients, and investigate the dynamic of the intestine and vaginal microbiome using metagenomic sequencing. This study was a single-centre, prospective, parallel-group, randomized controlled clinical trial. Participants were randomly assigned to the control or probiotic group using a 1:1 ratio. Results showed that there was no significant difference in BV cure rates between the probiotic and control groups at day 14, day 30, and day 90. In addition, in the BV conversion population, the percentage of people in a transition state was lower in the probiotic group at all three time-points. Hence, oral administration of L. gasseri TM13 and L. crispatus LG55 is effective in restoring the vaginal health of patients recovered from BV. Authors conclude that an individualised intervention approach should be developed to restore the vaginal health of patients recovering from BV.
Abstract
UNLABELLED Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV. CLINICAL TRIAL REGISTRATION https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.
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Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial.
Zhang, X, Chen, S, Zhang, M, Ren, F, Ren, Y, Li, Y, Liu, N, Zhang, Y, Zhang, Q, Wang, R
Nutrients. 2021;13(7)
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Constipation is a common complaint among people with depression and may negatively affect their quality of life. In association with this, previous studies have shown a correlation between the reduction of Lactobacillus or Bifidobacterium strains in the gut of patients with major depressive disorder. Thus, this two-arm, parallel-design, randomised, double-blinded, placebo-controlled trial examined the effects of supplementing fermented milk with Lacticaseibacillus paracasei Strain Shirota or LcS (previously known as Lactobacillus casei strain Shirota) on constipation in people with depression. Symptoms of constipation, stool problems, and depressive symptoms improved after 9 weeks of consuming fermented milk containing LcS. The abundance of Adlercreutzia, Megasphaera, and Veillonella increased significantly in the intervention group. In contrast, the abundance of bacteria related to mental disorders such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter significantly decreased after the intervention. After 9 weeks of intervention with LcS, a significant reduction in serum proinflammatory cytokines such as IL-1β, IL-6, and TNF-α was observed in patients with depression. The intervention group also showed a decrease in inflammation-causing bacteria, Surrerella, which correlated with a reduction in proinflammatory cytokines. The mechanisms driving the changes in gut microbial composition, depression, and gastrointestinal symptoms after LcS intervention need to be evaluated in more robust studies. Healthcare professionals can use the results of the study to better understand how probiotics can reduce constipation and depression and improve gut microbial composition.
Abstract
Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8-12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.
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Probiotics for prevention and treatment of respiratory tract infections in children: A systematic review and meta-analysis of randomized controlled trials.
Wang, Y, Li, X, Ge, T, Xiao, Y, Liao, Y, Cui, Y, Zhang, Y, Ho, W, Yu, G, Zhang, T
Medicine. 2016;95(31):e4509
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Respiratory tract infections (RTIs) are a leading cause of morbidity and mortality among children worldwide. Probiotics are thought to be able to balance the gut microbiota and interact with the immune system, which may promote resistance against pathogens. There are conflicting results from studies investigating the effect of probiotics on RTI infection. The aim of this systematic review and meta-analysis was to provide the latest and convincing evidence of the effect of probiotic consumption on RTIs in children. 32 studies were included in the qualitative analysis, and 23 in the quantitative meta-analysis. All trials were randomised, double-blinded, and placebo-controlled. Probiotic supplementation had a significant effect on the reduction of number of subjects having at least 1 respiratory symptom episode, on the number of days the children were ill and the number of days absent from day care/school. There was no significant statistical difference of illness episode duration. There was statistical heterogeneity among the trials, and subgroup analysis did not highlight the source of this. It was noted, however, that the probiotic strain, the duration of regimens, administration forms, doses, and follow-up times differed across the included studies, as did the age of children. The authors conclude that probiotic consumption may decrease the incidence and illness duration of RTIs, and that further research is needed to establish optimal probiotic strains, dosing, administration form, time of intervention, and long-time follow-up.
Abstract
BACKGROUND Respiratory tract infections (RTIs) represent one of the main health problems in children. Probiotics are viable bacteria that colonize the intestine and affect the host intestinal microbial balance. Accumulating evidence suggests that probiotic consumption may decrease the incidence of or modify RTIs. The authors systematically reviewed data from randomized controlled trials (RCTs) to investigate the effect of probiotic consumption on RTIs in children. METHODS MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for RCTs regarding the effect of probiotics on RTIs in children. The outcomes included number of children experienced with at least 1 RTI episode, duration of illness episodes, days of illness per subject, and school/day care absenteeism due to infection. A random-effects model was used to calculate pooled relative risks, or mean difference (MD) with the corresponding 95% confidence interval (CI). RESULTS A total of 23 trials involving 6269 children were eligible for inclusion in the systematic review. None of the trials showed a high risk of bias. The quality of the evidence of outcomes was moderate. The age range of subjects was from newborn to 18 years. The results of meta-analysis showed that probiotic consumption significantly decreased the number of subjects having at least 1 RTI episode (17 RCTs, 4513 children, relative risk 0.89, 95% CI 0.82-0.96, P = 0.004). Children supplemented with probiotics had fewer numbers of days of RTIs per person compared with children who had taken a placebo (6 RCTs, 2067 children, MD -0.16, 95% CI -0.29 to 0.02, P = 0.03), and had fewer numbers of days absent from day care/school (8 RCTs, 1499 children, MD -0.94, 95% CI -1.72 to -0.15, P = 0.02). However, there was no statistically significant difference of illness episode duration between probiotic intervention group and placebo group (9 RCTs, 2817 children, MD -0.60, 95% CI -1.49 to 0.30, P = 0.19). CONCLUSION Based on the available data and taking into account the safety profile of RCTs, probiotic consumption appears to be a feasible way to decrease the incidence of RTIs in children.