Abstract

Psoriasis is a chronic inflammatory skin disease with autoimmune pathological characteristics. Recent research has found a link between psoriasis, inflammation, and gut microbiota dysbiosis, and that probiotics and prebiotics provide benefits to patients. This 12-week open-label, single-center clinical trial evaluated the efficacy of probiotics (Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans (SC208), Bacillus licheniformis (SL307), and Bacillus clausii (SC109)) and precision prebiotics (fructooligosaccharides, xylooligosaccharides, and galactooligosaccharides) in patients with psoriasis receiving topical therapy, with an emphasis on potential metabolic, immunological, and gut microbiota changes. In total, 63 patients were evaluated, with the first 42 enrolled patients assigned to the intervention group and the next 21 assigned to the control group (2:1 ratio; non-randomized). There were between-group differences in several patient characteristics at baseline, including age, psoriasis severity (the incidence of severe psoriasis was greater in the intervention group than in the control group), the presence of nail psoriasis, and psoriatic arthritis, though it is not clear whether or how these differences may have affected the study findings. Patients with psoriasis receiving anti-psoriatic local therapy and probiotic and prebiotic supplementation performed better in measures of disease activity, including Psoriasis Area and Severity Index, Dermatology Life Quality Index, inflammatory markers, and skin thickness compared with those not receiving supplementation. Furthermore, in the 15/42 patients in the intervention group who received gut microbiota analysis, the gut microbiota changed favorably following 12 weeks of probiotic and prebiotic supplementation, with a shift towards an anti-inflammatory profile.

Abstract

Pediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + β acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.

Abstract

Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.

Abstract

To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations. What You Need to KnowWhat is the context:Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD.What is new:Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB−4) in only one year. A relation between the changes in these scores and gut microbiota changes was found.What is the impact:The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD.

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.

Abstract

BACKGROUND Probiotic supplements, by definition, provide a benefit to the host, but few studies have investigated the effect of probiotic supplements in healthy adult populations. PURPOSE The present, single arm, open label clinical trial, evaluated compositional and functional changes in the fecal microbiome of healthy adults after supplementation with a 14-strain probiotic. METHODS We analysed the effect of a 14-strain probiotic blend (Bacillus subtilis NCIMB 30223, Bifidobacterium bifidum NCIMB 30179, B. breve NCIMB 30180, B. infantis NCIMB 30181, B. longum NCIMB 30182, Lactobacillus helveticus NCIMB 30184, L. delbrueckii subsp. bulgaricus NCIMB 30186, Lacticaseibacillus paracasei NCIMB 30185, Lactiplantibacillus plantarum NCIMB 30187, Lacticaseibacillus rhamnosus NCIMB 30188, L. helveticus NCIMB 30224, Lactobacillus salivarius NCIMB 30225, Lactococcus lactis subsp. lactis NCIMB 30222, and Streptococcus thermophilus NCIMB 30189), on the faecal microbiota of healthy young adults (n=41) in a single arm study. The adults consumed 4 capsules daily of the 14 strain blend(8 billion colony forming units/day) for 8 weeks. Compositional and functional changes in faecal microbiota before and after supplementation were assessed using shotgun metagenomic sequencing. Fasting breath analysis, faecal biochemistry and bowel habits were also assessed. RESULTS In healthy adult participants, no significant changes to the overall alpha- or beta-diversity was observed after 8 weeks of multi-strain probiotic supplementation. However, in a simplified model that considered only time and individual differences, significant decreases (p < 0.05) in family Odoribacteraceae and Bacteroidaceae abundance and a significant increase (p < 0.05) in genus Megamonas abundance were observed. At a functional level, there were significant changes in functional gene abundance related to several functional pathways, including phenylalanine metabolism, O-antigen nucleotide sugar biosynthesis, bacterial chemotaxis, and flagellar assembly. No significant changes in stool form or frequency, fecal biochemistry, or methane and hydrogen breath tests were observed. CONCLUSION In healthy young adults, overall alpha- and beta-diversity did not change in response to probiotic intake even though modest compositional changes at the family and genus level were observed. However, at functional level, results identified changes in gene abundance for several functional pathways.

Abstract

BACKGROUND Maternal diet influences the milk composition, yet little information is available on the impact of maternal diet on milk miRNAs expression. Further, the association of human milk miRNAs to maternal diet and milk microbiota is not explored. In addition, the role of milk miRNAs on the infant gut microbiota, infant growth and development has not been investigated. METHODS Milk samples were collected from 60 healthy lactating women at ≤15d post-partum, HTG transcriptome assay was performed to examine milk miRNA profile. Maternal clinical and dietary clusters information were available and infant anthropometric measures were followed up to one year of age. Milk and infant microbiota were analyzed by 16S rRNA gene sequencing and integrative multi-omics data analysis was performed to identify potential association between microRNA, maternal dietary nutrients and microbiota. RESULTS Discriminant analysis revealed that the milk miRNAs were clustered into groups according to the maternal protein source. Interestingly, 31 miRNAs were differentially expressed (P adj < 0.05) between maternal dietary clusters (Cluster 1: enriched in plant protein and fibers and Cluster 2: enriched in animal protein), with 30 miRNAs downregulated in the plant protein group relative to animal protein group. Pathway analysis revealed that the top enriched pathways (P adj < 0.01) were involved in cell growth and proliferation processes. Furthermore, significant features contributing to the clustering were associated with maternal dietary nutrients and milk microbiota (r > 0.70). Further, miR-378 and 320 family miRNAs involved in adipogenesis were positively correlated to the infant BMI-z-scores, weight, and weight for length-z-scores at 6 months of age. CONCLUSIONS Maternal dietary source impacts the milk miRNA expression profile. Further, miRNAs were associated with maternal dietary nutrients, milk microbiota and to the infant gut microbiota and infant growth and development. CLINICAL TRIAL The study is registered in ClinicalTrials.gov. The identification number is NCT03552939.

Abstract

PURPOSE Bile acid (BA) metabolism by intestinal bacteria is associated with the risk of gastrointestinal diseases; additionally, its control has become a modern strategy for treating metabolic diseases. This cross-sectional study investigated the influence of defecation status, intestinal microbiota, and habitual diet on fecal BA composition in 67 community-dwelling young participants. METHODS Feces were collected for intestinal microbiota and BA analyses; data about defecation status and dietary habits were collected using the Bristol stool form scales and a brief-type self-administered diet history questionnaire, respectively. The participants were categorized into four clusters based on their fecal BA composition, according to cluster analysis, and tertiles based on deoxycholic acid (DCA) and lithocholic acid (LCA) levels. RESULTS The high primary BA (priBA) cluster with high fecal cholic acid (CA) and chenodeoxycholic acid (CDCA) levels had the highest frequency of normal feces, whereas the second BA (secBA) cluster with high levels of fecal DCA and LCA had the lowest. Alternately, the high-priBA cluster had a distinct intestinal microbiota, with higher Clostridium subcluster XIVa and lower Clostridium cluster IV and Bacteroides. The low-secBA cluster with low fecal DCA and LCA levels had the lowest animal fat intake. Nevertheless, the insoluble fiber intake of the high-priBA cluster was significantly higher than that of the high-secBA cluster. CONCLUSION High fecal CA and CDCA levels were associated with distinct intestinal microbiota. Conversely, high levels of cytotoxic DCA and LCA were associated with increased animal fat intake and decreased frequency of normal feces and insoluble fiber intake. CLINICAL TRIAL REGISTRY University Hospital Medical Information Network (UMIN) Center system (UMIN000045639); date of registration: 15/11/2019.

Abstract

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. The existing data suggest that early diagnosis and intervention can improve ASD outcomes. The causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. There is an increasing recognition that ASD might be associated with oxidative stress through several mechanisms including abnormal metabolism (lipid peroxidation) and the toxic buildup of reactive oxygen species (ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. This open-label pilot study investigates the tolerability and effectiveness of oral supplementation with OpitacTM gluthathione as a treatment for patients with ASD. The various aspects of glutathione OpitacTM glutathione bioavailability were examined when administered by oral routes. The absorption of glutathione from the gastrointestinal tract has been recently investigated. The results of this case series suggest that oral glutathione supplementation may improve oxidative markers, but this does not necessarily translate to the observed clinical improvement of subjects with ASD. The study reports a good safety profile of glutathione use, with stomach upset reported in four out of six subjects. This article discusses the role of the gut microbiome and redox balance in ASD and notes that a high baseline oxidative burden may make some patients poor responders to glutathione supplementation. In conclusion, an imbalance in redox reactions is only one of the many factors contributing to ASD, and further studies are necessary to investigate other factors, such as impaired neurotransmission, immune dysregulation in the brain, and mitochondrial dysfunction.

Abstract

BACKGROUND Time-restricted feeding (TRF) has become a popular weight loss method in recent years. It is widely used in the nutritional treatment of normal obese people and obese people with chronic diseases such as diabetes mellitus and hypertension, and has shown many benefits. However, most TRF studies have excluded chronic kidney disease (CKD) patients, resulting in a lack of sufficient evidence-based practice for the efficacy and safety of TRF therapy for CKD. Therefore, we explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD through this pilot study, and observe patient compliance to assess the feasibility of the therapy. METHODS This is a prospective, non-randomized controlled short-term clinical trial. We recruited overweight and obese patients with CKD stages 3-4 from an outpatient clinic and assigned them to either a TRF group or a control diet (CD) group according to their preferences. Changes in renal function, other biochemical data, anthropometric parameters, gut microbiota, and adverse events were measured before the intervention and after 12 weeks. RESULTS The change in estimated glomerular filtration rate (eGFR) before and after intervention in the TRF group (Δ = 3.1 ± 5.3 ml/min/1.73m2) showed significant improvement compared with the CD group (Δ = -0.8 ± 4.4 ml/min/1.73m2). Furthermore, the TRF group had a significant decrease in uric acid (Δ = -70.8 ± 124.2 μmol/L), but an increase in total protein (Δ = 1.7 ± 2.5 g/L), while the changes were inconsistent for inflammatory factors. In addition, the TRF group showed a significant decrease in body weight (Δ = -2.8 ± 2.9 kg) compared to the CD group, and body composition indicated the same decrease in body fat mass, fat free mass and body water. Additionally, TRF shifted the gut microbiota in a positive direction. CONCLUSION Preliminary studies suggest that overweight and obese patients with moderate-to-severe CKD with weight loss needs, and who were under strict medical supervision by healthcare professionals, performed TRF with good compliance. They did so without apparent adverse events, and showed efficacy in protecting renal function. These results may be due to changes in body composition and alterations in gut microbiota.