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Diet is both a modulator of the gastrointestinal microbiota and an important therapy in irritable bowel syndrome (IBS). We aimed to comprehensively (i) identify diet-microbiota associations in adults with IBS consuming habitual diet; (ii) assess the impact of two nutritional interventions on the microbiota; and (iii) determine whether baseline microbiota can predict clinical response to diet or probiotic intervention. Data were analyzed from 95 individuals with IBS participating in a previously published 4-week 2x2 factorial design randomized controlled trial investigating the impact of the low FODMAP diet (LFD) and co-administration of a probiotic. Diet was assessed at four hierarchical levels and partial 16S rRNA gene sequencing was used to profile the microbiota. There were numerous diet-microbiota associations especially at the nutrient level, including a negative association between protein and Bifidobacterium abundance (r s = −0.358, p < 0.001). After correction for multiple testing, the significance for this association (q = 0.237) and all others was lost. Low FODMAP diet led to changes in abundance of major saccharolytic genera compared with sham diet, including higher Bacteroides (LFD 34.1% (15.7%) vs sham 23.3% (15.2%), q = 0.01) and lower Bifidobacterium (0.9% (1.0%) vs 2.1%, (2.5%) q = 0.029). Compared with placebo, probiotic supplementation led to higher Lactobacillus (probiotic 0.08% (0.1%) vs placebo 0.03% (0.2%), q < 0.001), and Streptococcus abundance (2.0% (2.2%) vs 0.6% (1.2%), q = 0.001). The probiotic treatment buffered the impact of the low FODMAP diet on Bifidobacterium. Baseline microbiota did not predict clinical response to either intervention. Although diet modifies the gut microbiota, bivariate correlation analysis may only provide a limited explanation of the complex diet interactions with individual gut bacteria in IBS. Some diet interventions modify the microbiota in IBS. ISRCTN (http://www.isrctn.com) Registered under ISRCTN registry identifier no.ISRCTN02275221. [ABSTRACT FROM AUTHOR]

Background & Aims Dietary restriction of fermentable carbohydrates (a low FODMAP diet) has been reported to reduce symptoms in some patients with irritable bowel syndrome (IBS). We performed a randomized, placebo-controlled study to determine its effects on symptoms and the fecal microbiota in patients with IBS. Methods We performed a 2×2 factorial trial of 104 patients with IBS (18–65 years old), based on the Rome III criteria, at 2 hospitals in the United Kingdom. Patients were randomly assigned (blinded) to groups given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks, along with a placebo or multistrain probiotic formulation, resulting in 4 groups (27 receiving sham diet/placebo, 26 receiving sham diet/probiotic, 24 receiving low FODMAP diet /placebo, and 27 receiving low FODMAP diet/probiotic). The sham diet restricted a similar number of staple and non-staple foods as the low FODMAP diet; the diets had similar degrees of difficulty to follow. Dietary counselling was given to patients in all groups and data on foods eaten and compliance were collected. The incidence and severity of 15 gastrointestinal symptoms and overall symptoms were measured daily for 7 days before the study period; along with stool frequency and consistency. At baseline, global and individual symptoms were measured, along with generic and disease-specific health-related quality of life, using standard scoring systems. All data were collected again at 4 weeks, and patients answered questions about adequate symptom relief. Fecal samples were collected at baseline and after 4 weeks and analyzed by quantitative PCR and 16S rRNA sequencing. The co-primary endpoints were adequate relief of symptoms and stool Bifidobacterium species abundance at 4 weeks. Results There was no significant interaction between the interventions in adequate relief of symptoms ( P = .52) or Bifidobacterium species ( P = .68). In the intention-to-treat analysis, a higher proportion of patients in the low FODMAP diet had adequate symptom relief (57%) than in the sham diet group (38%), although the difference was not statistically significant ( P = .051). In the per-protocol analysis, a significantly higher proportion of patients on the low FODMAP diet had adequate symptom relief (61%) than in the sham diet group (39%) ( P = .042). Total mean IBS-Severity Scoring System score was significantly lower for patients on the low FODMAP diet (173 ± 95) than the sham diet (224 ± 89) ( P = .001), but not different between those given probiotic (207 ± 98) or placebo (192 ± 93) ( P = .721) Abundance of Bifidobacterium species was lower in fecal samples from patients on the low FODMAP diet (8.8 rRNA genes/g) than patients on the sham diet (9.2 rRNA genes/g) ( P = .008), but higher in patients given probiotic (9.1 rRNA genes/g) than patients given placebo (8.8 rRNA genes/g) ( P = .019). There was no effect of the low FODMAP diet on microbiota diversity in fecal samples. Conclusions In a placebo-controlled study of patients with IBS, a low FODMAP diet associates with adequate symptom relief and significantly reduced symptom scores compared with placebo. It is not clear whether changes resulted from collective FODMAP restriction or removal of a single component, such as lactose. Co-administration of the multistrain probiotic increased numbers of Bifidobacterium species, compared with placebo, and might be given to restore these bacteria to patients on a low FODMAP diet. Trial registration no: ISRCTN02275221. [ABSTRACT FROM AUTHOR]

[Display omitted] • Wolffia globosa an emerging functional food, targets obesity and metabolic disease. • Wolffia globosa rich in fiber and polyphenols modulates the gut microbiome. • Wolffia globosa increases microbiota phenolic acid and SCFA production in vitro. • Microbiome modulation may underpin certain health effects of Wolffia globosa ingestion. Mankai® is a cultivated strain of Wolffia globosa an aquatic plant of the family Lemnaceae commonly known as Duckweeds. Recent studies suggest that consumption of a Mankai® enriched diet may provide positive health effects by decreasing body weight and improving glucose homeostasis and plasma lipid profiles. However, the effects of Mankai® alone on the composition and metabolic output of the human gut microbiota has not been fully investigated. Here, Mankai® was digested and fermented in vitro using a batch culture model of the proximal colon. Inulin and cellulose were used as readily and poorly fermentable control fibers respectively. Mankai® significantly stimulated the production of phenolic metabolites and short chain fatty acids by the gut microbiota (p<0.05). Three major microbial metabolites, 3-4-hydroxyphenyl propionic acid, 3-3-hydroxyphenyl propanoic acid and protocatechuic acid were significantly increased after 24 h fermentation. Moreover, Mankai® treatment lowered the overall microbial diversity (p<0.05), in line with a selective microbiome modulation. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase. In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3–4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6–14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet. Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6–14 (aFMT, 30.4% vs placebo, 40.6%; P =.28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P =.02), but not in the dietary guidelines (P =.57) or Mediterranean diet (P =.64) groups (P for the interaction =.03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P =.01) and insulin rebound (aFMT, –1.46 ± 3.6 μIU/mL vs placebo, 1.64 ± 4.7 μIU/mL; P =.04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction =.04 and.03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss–associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet–induced regain phase (all, P <.05). Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186. [ABSTRACT FROM AUTHOR]

Recent evidence suggests the substantial pathogenic role of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in the development of low-grade chronic inflammatory response, known as "metaflammation," which contributes to obesity and type 2 diabetes. In this study, we investigated the effects of the JAK1/2 inhibitor baricitinib, recently approved for the treatment of rheumatoid arthritis, in a murine high-fat-high sugar diet model. Male C57BL/6 mice were fed with a control normal diet (ND) or a high-fat-high sugar diet (HD) for 22 weeks. A sub-group of HD fed mice was treated with baricitinib (10 mg/kg die, p.o.) for the last 16 weeks (HD + Bar). HD feeding resulted in obesity, insulin-resistance, hypercholesterolemia and alterations in gut microbial composition. The metabolic abnormalities were dramatically reduced by chronic baricitinib administration. Treatment of HD mice with baricitinib did not change the diet-induced alterations in the gut, but restored insulin signaling in the liver and skeletal muscle, resulting in improvements of diet-induced myosteatosis, mesangial expansion and associated proteinuria. The skeletal muscle and renal protection were due to inhibition of the local JAK2-STAT2 pathway by baricitinib. We also demonstrated that restored tissue levels of JAK2-STAT2 activity were associated with a significant reduction in cytokine levels in the blood. In summary, our data suggest that the JAK2-STAT2 pathway may represent a novel candidate for the treatment of diet-related metabolic derangements, with the potential for EMA- and FDA-approved JAK inhibitors to be repurposed for the treatment of type 2 diabetes and/or its complications. • The Jak/Stat signaling pathway is dysregulated in metabolic diseases. • The Jak2 inhibitor baricitinib exerts multi-organ protection against diet-induced metabolic derangements. • Targeting the chronic metabolic inflammation (termed metaflammation) represents an effective strategy for metabolic diseases. [ABSTRACT FROM AUTHOR]