Prebiotics for induction and maintenance of remission in ulcerative colitis.

BACKGROUND: People affected by ulcerative colitis (UC) are interested in dietary therapies as treatments that can improve their health and quality of life. Prebiotics are a category of food ingredients theorised to have health benefits for the gastrointestinal system through their effect on the growth and activity of intestinal bacteria and probiotics. OBJECTIVES: To assess the efficacy and safety of prebiotics for the induction and maintenance of remission in people with active UC. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP on 24 June 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) on people with UC. We considered any type of standalone or combination prebiotic intervention, except those prebiotics combined with probiotics (known as synbiotics), compared to any control intervention. We considered interventions of any dose and duration. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We included 9 RCTs involving a total of 445 participants. Study duration ranged from 14 days to 2 to 3 months for induction and 1 to 6 months for maintenance of remission. All studies were on adults. Five studies were on people with mild to moderate active disease, three in remission or mild activity, and one did not mention. We judged only one study as at low risk of bias in all areas. Two studies compared prebiotics with placebo for induction of remission. We cannot draw any conclusions about clinical remission (70% versus 67%; risk ratio (RR) 1.05, 95% confidence interval (CI) 0.57 to 1.94); clinical improvement (mean Rachmilewitz score on day 14 of 4.1 versus 4.5; mean difference (MD) -0.40, 95% CI -2.67 to 1.87); faecal calprotectin levels (mean faecal calprotectin on day 14 of 1211 µg/mL versus 3740 µg/mL; MD -2529.00, 95% CI -6925.38 to 1867.38); interleukin-8 (IL-8) levels (mean IL-8 on day 7 of 2.9 pg/mL versus 5.0 pg/mL; MD -2.10, 95% CI -4.93 to 0.73); prostaglandin E2 (PGE-2) levels (mean PGE-2 on day 7 of 7.1 ng/mL versus 11.5 ng/mL; MD -4.40, 95% CI -20.25 to 11.45); or withdrawals due to adverse events (21% versus 8%; RR 2.73, 95% CI 0.51 to 14.55). All evidence was of very low certainty. No other outcomes were reported. Two studies compared inulin and oligofructose 15 g with inulin and oligofructose 7.5 g for induction of remission. We cannot draw any conclusions about clinical remission (53% versus 12.5%; RR 4.27, 95% CI 1.07 to 16.96); clinical improvement (67% versus 25%; RR 2.67, 95% CI 1.06 to 6.70); total adverse events (53.5% versus 31%; RR 1.71, 95% CI 0.72 to 4.06); or withdrawals due to adverse events (13% versus 25%; RR 0.53, 95% CI 0.11 to 2.50). All evidence was of very low certainty. No other outcomes were reported. One study compared prebiotics and anti-inflammatory therapy with anti-inflammatory therapy alone for induction of remission. We cannot draw any conclusions about clinical improvement (mean Lichtiger score at 4 weeks of 6.2 versus 10.3; MD -4.10, 95% CI -8.14 to -0.06) or serum C-reactive protein (CRP) levels (mean CRP levels at 4 weeks 0.55 ng/mL versus 0.50 ng/mL; MD 0.05, 95% CI -0.37 to 0.47). All evidence was of very low certainty. No other outcomes were reported. Three studies compared prebiotics with placebo for maintenance of remission. There may be no difference between groups in rate of clinical relapse (44% versus 33%; RR 1.36, 95% CI 0.79 to 2.31), and prebiotics may lead to more total adverse events than placebo (77% versus 46%; RR 1.68, 95% CI 1.18 to 2.40). The evidence was of low certainty. We cannot draw any conclusions about clinical improvement (mean partial Mayo score at day 60 of 0.428 versus 1.625; MD -1.20, 95% CI -2.17 to -0.22); faecal calprotectin levels (mean faecal calprotectin level at day 60 of 214 µg/mL versus 304 µg/mL; MD -89.79, 95% CI -221.30 to 41.72); quality of life (mean Inflammatory Bowel Disease Questionnaire (IBDQ) score at day 60 of 193.5 versus 188.0; MD 5.50, 95% CI -8.94 to 19.94); or withdrawals due to adverse events (28.5% versus 11%; RR 2.57, 95% CI 1.15 to 5.73). The evidence for these outcomes was of very low certainty. No other outcomes were reported. One study compared prebiotics with synbiotics for maintenance of remission. We cannot draw any conclusions about quality of life (mean IBDQ score at 4 weeks 182.4 versus 176.1; MD 6.30, 95% CI -6.61 to 19.21) or withdrawals due to adverse events (23% versus 20%; RR 1.13, 95% CI 0.48 to 2.62). All evidence was of very low certainty. No other outcomes were reported. One study compared prebiotics with probiotics for maintenance of remission. We cannot draw any conclusions about quality of life (mean IBDQ score at 4 weeks 182.4 versus 168.6; MD 13.60, 95% CI 1.22 to 25.98) or withdrawals due to adverse events (22.5% versus 22.5%; RR 1.00, 95% CI 0.44 to 2.26). All evidence was of very low certainty. No other outcomes were reported. AUTHORS' CONCLUSIONS: There may be no difference in occurrence of clinical relapse when adjuvant treatment with prebiotics is compared with adjuvant treatment with placebo for maintenance of remission in UC. Adjuvant treatment with prebiotics may result in more total adverse events when compared to adjuvant treatment with placebo for maintenance of remission. We could draw no conclusions for any of the other outcomes in this comparison due to the very low certainty of the evidence. The evidence for all other comparisons and outcomes was also of very low certainty, precluding any conclusions. It is difficult to make any clear recommendations for future research based on the findings of this review given the clinical and methodological heterogeneity among studies. It is recommended that a consensus is reached on these issues prior to any further research.

Prebiotic inulin as a treatment of obesity related nonalcoholic fatty liver disease through gut microbiota: a critical review.

The microbial-derived products, including short chain fatty acids, lipopolysaccharide and secondary bile acids, have been shown to participate in the regulation of hepatic lipid metabolism. Previous studies have demonstrated that prebiotics, such as oligosaccharide and inulin, have abilities to change the concentration of microbial-derived products through modulating the microbial community structure, thus controlling body weight and alleviating hepatic fat accumulation. However, recent evidence indicates that there are individual differences in host response upon inulin treatment due to the differences in host microbial composition before dietary intervention. Probably it is because of the multiple relationships among bacterial species (e.g., competition and mutualism), which play key roles in the degradation of inulin and the regulation of microbial structure. Thereby, analyzing the composition and function of initial gut microbiota is essential for improving the efficacy of prebiotics supplementation. Furthermore, considering that different structures of polysaccharides can be used by different microorganisms, the chemical structure of processed inulin should be tested before using prebiotic inulin to treat obesity related nonalcoholic fatty liver disease.

Effects of inulin supplementation on inflammatory biomarkers and clinical symptoms of women with obesity and depression on a calorie-restricted diet: a randomised controlled clinical trial.

Major depressive disorder (MDD) is regarded as an inflammatory disorder. Gut microbiota dysbiosis, observed in both MDD and obesity, leads to endotoxemia and inflammatory status, eventually exacerbating depressive symptoms. Manipulation of gut microbiota by prebiotics might help alleviate depression. The present study aimed to investigate the effects of inulin supplementation on psychological outcomes and biomarkers of gut permeability, endotoxemia, inflammation, and brain-derived neurotrophic factor (BDNF) in women with obesity and depression on a calorie-restricted diet. In a double-blind randomised clinical trial, forty-five women with obesity and MDD were allocated to receive 10 g/d of either inulin or maltodextrin for 8 weeks; all the patients followed a healthy calorie restricted diet as well. Anthropometric measures, dietary intakes, depression, and serum levels of zonulin, lipopolysaccharide (LPS), inflammatory biomarkers (TNF-α, IL-10, monocyte chemoattractant protein-1, toll-like receptor-4 and high-sensitivity C-reactive protein), and BDNF were assessed at baseline and end of the study. Weight and Hamilton Depression Rating Scale (HDRS) scores decreased in both groups; between-group differences were non-significant by the end of study (P = 0·333 for body weight and P = 0·500 for HDRS). No between-group differences were observed for the other psychological outcomes and serum biomarkers (P > 0·05). In this short-term study, prebiotic supplementation had no significant beneficial effects on depressive symptoms, gut permeability, or inflammatory biomarkers in women with obesity and depression.

Effects of inulin-type fructans with different degrees of polymerization on inflammation, oxidative stress and endothelial dysfunction in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with several cardiovascular risk factors. Prebiotics were proposed to beneficially affect risk factors associated with metabolic disorders. The aim of this study was to investigate and compare the effects of inulin-type fructans (ITFs), as well-studied prebiotics, with different degrees of polymerization, on markers of inflammation, oxidative stress and endothelial dysfunction in PCOS patients. DESIGN: A randomized, double-blind, placebo-controlled trial. PATIENTS: Seventy-five PCOS women were randomly assigned to receive 10 g/day of either high-performance inulin (HPI) or oligofructose-enriched inulin (OEI) or placebo for 12 weeks. MEASUREMENTS: Biochemical indices and blood pressure levelswere assessed before and after the intervention. RESULTS: In the intent-to-treat analysis, high-sensitive C-reactive protein (hs-CRP) decreased in HPI and OEI groups, over the 12 weeks, and the changes were significant in the HPI group, compared to placebo (changes from baseline in the HPI group: -0.11 vs. placebo group: 0.004 mg/L [conversion factor to SI units (nmol/L): 9/5238]; p = .007). Serum levels of nitric oxide (NO) increased, and endothelin-1 and total oxidant status decreased in HPI and OEI groups, at the end of the trial; however, these changes were not significantly compared to placebo (p = .07, .36 and .22, respectively). No differences in systolic and diastolic blood pressure were found. Per-protocol analysis (n = 68) yielded consistent results for all endpoints, with the exception that the significant effect of ITFs on serum hs-CRP levels in the unadjusted ITT analysis became nonsignificant in the per-protocol analysis (p = .06). CONCLUSION: A 12-week supplementation with long-chain ITFs had favourable effects on inflammatory status among PCOS patients.

Inulin-type fructans change the gut microbiota and prevent the development of diabetic nephropathy.

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, and few treatment options that prevent the progressive loss of renal function are available. Studies have shown that dietary fiber intake improves kidney diseases and metabolism-related diseases, most likely through short-chain fatty acids (SCFAs). The present study aimed to examine the protective effects of inulin-type fructans (ITFs) on DN through 16 S rRNA gene sequencing, gas chromatographymass spectrometry (GCMS) analysis and fecal microbiota transplantation (FMT). The results showed that ITFs supplementation protected against kidney damage in db/db mice and regulated the composition of the gut microbiota. Antibiotic treatment and FMT experiments further demonstrated a key role of the gut microbiota in mediating the beneficial effects of ITFs. The ITFs treatment-induced changes in the gut microbiota led to an enrichment of SCFA-producing bacteria, especially the genera Akkermansia and Candidatus Saccharimonas, which increased the fecal and serum acetate concentrations. Subsequently, acetate supplementation improved glomerular damage and renal fibrosis by attenuating mitochondrial dysfunction and reducing toxic glucose metabolite levels. In conclusion, ITFs play a renoprotective role by modulating the gut microbiota and increasing acetate production. Furthermore, acetate mediates renal protection by regulating glucose metabolism, decreasing glycotoxic product levels and improving mitochondrial function.

The effects of co-administration of probiotics and prebiotics on chronic inflammation, and depression symptoms in patients with coronary artery diseases: a randomized clinical trial.

BACKGROUND: It has been shown that dysbiosis might have a role in developing of chronic inflammation and depression. In this study, we are interested in exploring of anti-inflammatory and anti-depressant effects of Lactobacillus Rhamnosus G (LGG), a probiotic strain, alone or in combination with a prebiotic, Inulin, in patients with coronary artery disease (CAD). METHODS: This randomized, double-blind clinical trial was held on 96 patients with CAD. Patients were randomly allocated into four different groups: LGG [a capsule/day, contained 1.9 × 109 colony-forming unit of Lactobacillus Rhamnosus G], inulin (15 g/day), co-supplemented (LGG and inulin), and placebo. Participants consumed the supplements for two months. Beck Depression Inventory (BDI), MacNew questionnaire and Spielberger state-trait anxiety inventory (STAI-Y) were used to assess depression, quality of life and anxiety, respectively. Serum levels of C-reactive protein (hs-CRP), lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, and Interleukin (IL)-10 were also measured. RESULTS: Probiotic-Inulin Co-supplementation significantly decreased BDI (-11.52 ± 0+3.20 vs. +2.97 ± 0.39, P = 0.001), STAI-state (-17.63 ± 3.22 vs. -0.60 ± 0.33, P = 0.021), and STAI-trait (-24.31 ± 7.41 vs. -1.45 ± 0.66, P = 0.020) scores, hs-CRP (-1.69 ± 0+66 vs. +0.82 ± 0.39 mg/dL, P = 0.020), LPS (-22.02 ± 5.40 vs. +0.31 ± 0.18 (EU/L), P = 0.047), and TNF-α (-25.05 ± 7.41 vs. +0.79 ± 0.71 (ng/L), P = 0.032) in comparison to placebo. CONCLUSION: Co-supplementation of probiotics and inulin in CAD subjects for eight weeks had beneficial effects on depression, anxiety, and inflammatory biomarkers. Adding inulin to probiotic supplements improved psychological outcomes and inflammatory biomarkers more effectively than two supplements separately.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20180712040438N4..

Overall Structural Alteration of Gut Microbiota and Relationships with Risk Factors in Patients with Metabolic Syndrome Treated with Inulin Alone and with Other Agents: An Open-Label Pilot Study.

Objective: The relative contribution of some products with prebiotic effects, such as inulin, together with medications specific to the human gut microbiome has not been comprehensively studied. The present study determined the potential for manipulating populations in the gut microbiome using inulin alone and combined with other agents in individuals with metabolic syndrome (MetS). The study also assessed whether there is relationship variability in multiple clinical parameters in response to intervention with the changes in the gut milieu. Participants/Methods. This single-centre, single-blinded, randomised community-based pilot trial randomly assigned 60 patients (mean age, 46.3 y and male, 43%) with MetS to receive either inulin, inulin+traditional Chinese medicine (TCM), or inulin+metformin for 6 months. Lipid profiles, blood glucose, and uric acid (UA) levels were analysed in venous blood samples collected after overnight fast of 8 h at baseline and at the end of the follow-up period. Microbiota from stool samples were taxonomically analysed using 16S RNA amplicon sequencing, and an integrative analysis was conducted on microbiome and responsiveness data at 6 months. Results: The results of 16S rRNA sequencing showed that inulin resulted in a higher proportion of Bacteroides at the endpoint compared with inulin+TCM and inulin+metformin (p = 0.024). More Romboutsia (p = 0.043), Streptococcus (p < 0.001), and Holdemanella (p = 0.011) were found in inulin+TCM and inulin+metformin samples. We further identified gut microbiota relationships with lipids, UA, and glucose that impact the development of MetS. Conclusion: Among the groups, inulin alone or combined with metformin or TCM altered specific gut microbiota taxa but not the general diversity. Accordingly, we analysed metabolites associated with microbiota that might provide more information about intrinsic differences. Consequently, a reliable method could be developed for treating metabolic syndrome in the future.

[Efficacy of newly developed kombucha-based specialized food product for treatment of constipation-predominant irritable bowel syndrome].

According to studies, the prevalence of constipation in the population can reach 27% due to the low intake of dietary fiber. Increasing dietary fiber intake can improve bowel movements. The aim of the study was to assess the efficacy of a non-alcoholic fermented pasteurized kombucha drink enriched with inulin and vitamins in patients with constipation-predominant irritable bowel syndrome (IBS). Material and methods. The study (NCT05164861) was approved by Local Ethics Committee and enrolled subjects with IBS (according to ROME IV). The subjects were randomized to receive either 220 ml of a non-alcoholic drink, based on pasteurized kombucha (KG), enriched with inulin (1.15 g/100 ml) or 220 ml water (control group, CG), for 10 days. Standard examination included evaluation of stool frequency (bowel movements per day), stool form (with the Bristol stool scale) and evaluation of concomitant symptoms (abdominal pain/discomfort, abdominal fullness, bloating, and feeling of incomplete bowel emptying) with the use of 5-point Likert scale before (BL) and 10 days after the start of intervention (EOT). Using visual analog scales (VAS), the palatability of the studied food was assessed at the beginning and end of the observation period. Results. Significant increase of stool frequency was found at the EOT compared to BL in KG (n=20), Mean±SD: 0.60±0.31 to 0.85±0.19 times/day; p=0.004, while there was no change in CG (n=20): 0.63±0.33 vs 0.72±0.28, p=0.6. Mean values of stool scale form increased in KG (3.0±1.2 to 4.4±1.0, p=0.001), while remained unchanged in CG (2.9±1.2 vs 3.4±1.2, p=0.6). Mean values of the Bristol stool scale in KG and CG differed significantly at EOT (p=0.018). Significant decrease in mean values of incomplete bowel emptying feeling was found in KG (1.88±0.78 at BL vs 1.41±0.56 points at EOT, p=0.015), but not in the control group. There were no statistically significant differences between patient's reports of the studied groups for other symptoms (bitterness and dryness in the mouth, heartburn, nausea, abdominal pain and heaviness in the stomach after eating). Conclusion. The effectiveness of a pasteurized fermented non-alcoholic drink based on kombucha enriched with inulin has been proven by reducing the intensity of complaints significant for constipation, normalizing the frequency and consistency of stools.

Discovery of the gut microbial signature driving the efficacy of prebiotic intervention in obese patients.

OBJECTIVE: The gut microbiota has been proposed as an interesting therapeutic target for metabolic disorders. Inulin as a prebiotic has been shown to lessen obesity and related diseases. The aim of the current study was to investigate whether preintervention gut microbiota characteristics determine the physiological response to inulin. DESIGN: The stools from four obese donors differing by microbial diversity and composition were sampled before the dietary intervention and inoculated to antibiotic-pretreated mice (hum-ob mice; humanised obese mice). Hum-ob mice were fed with a high-fat diet and treated with inulin. Metabolic and microbiota changes on inulin treatment in hum-ob mice were compared with those obtained in a cohort of obese individuals supplemented with inulin for 3 months. RESULTS: We show that hum-ob mice colonised with the faecal microbiota from different obese individuals differentially respond to inulin supplementation on a high-fat diet. Among several bacterial genera, Barnesiella, Bilophila, Butyricimonas, Victivallis, Clostridium XIVa, Akkermansia, Raoultella and Blautia correlated with the observed metabolic outcomes (decrease in adiposity and hepatic steatosis) in hum-ob mice. In addition, in obese individuals, the preintervention levels of Anaerostipes, Akkermansia and Butyricicoccus drive the decrease of body mass index in response to inulin. CONCLUSION: These findings support that characterising the gut microbiota prior to nutritional intervention with prebiotics is important to increase the positive outcome in the context of obesity and metabolic disorders.

Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

PURPOSE: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). METHODS: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). RESULTS: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1ß & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. CONCLUSION: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link.

Inulin-type fructans supplementation improves glycemic control for the prediabetes and type 2 diabetes populations: results from a GRADE-assessed systematic review and dose-response meta-analysis of 33 randomized controlled trials.

BACKGROUND: Currently, many clinical trials have shown that inulin-type fructans (ITF) supplementation is associated with glycemic control; nevertheless, the results are inconclusive. The aim of this meta-analysis of randomized controlled trials was to assess the effects of ITF supplementation on glycemic control. METHODS: PubMed, EMBASE and the Cochrane Library were searched for eligible articles up to March 6, 2019. A random-effects model was used to analyze the pooled results, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to assess the quality of evidence. The dose-response model was used to recommend the daily dose and duration for ITF supplementation. RESULTS: Thirty-three trials involving 1346 participants were included. Overall, ITF supplementation could significantly reduce concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR). In the prediabetes and type 2 diabetes (T2DM) population, a more significant reduction in FBG [weighted mean difference (WMD): - 0.60 mmol/l; 95% CI - 0.71, - 0.48 mmol/l; high rate], HbA1c (WMD: - 0.58%; 95% CI - 0.83, - 0.32%; high rate), FINS (WMD: - 1.75 µU/ml; 95% CI - 2.87, - 0.63 µU/ml; low rate), and HOMA-IR (WMD: - 0.69; 95% CI - 1.10, - 0.28; low rate) were observed, and ITF supplementation with a daily dose of 10 g for a duration of 6 weeks and longer was recommended. Moreover, subgroup analyses suggested that the effects of glycemic control were significantly influenced by the sex of the subjects and the type and the method of intake of ITF. CONCLUSIONS: Our analyses confirmed that these four main glycemic indicators were significantly reduced by ITF supplementation, particularly in the prediabetes and T2DM population. Evidence supports that reasonable administration of ITF supplementation may have potential clinical value as an adjuvant therapy for prediabetes and T2DM management. Trial registration The trial was registered at PROSPERO as CRD42018115875 on November 23, 2018.

Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice.

Polycystic ovary syndrome (PCOS) represents an endocrine disorder, which is closely related with gut microbiota. Inulin, a kind of probiotics, has been proven to alleviate gut microbiota dysbiosis. Metformin, a biguanide agent, shows beneficial effects on chronic metabolic diseases. Our objective was to assess the effects and associated mechanisms of inulin and metforin on attenuation of PCOS in mice. Mice were divided into 4 groups: control group (CON), model group (MOD), inulin group (INU), metformin group (MET). The last three groups were fed 6 mg of dehydroepiandrosterone (DHEA) per 100 g body weight and 60% high-fat diet to generate mice model. After 21 days of intervention, mice were euthanized and associated indications were investigated. Body weight (BW) and testosterone (T) levels were significantly decreased, but estradiol (E2) levels were increased in INU or MET group, respectively. Ovary HE staining demonstrated that inulin or metformin ameliorated PCOS morphology. Inflammatory indicators from plasma and ovary including TNF-α, IL-6, and IL-17A were decreased in INU or MET group. Moreover, IL-10 in ovary of INU or MET group was increased. Sequencing and analysis of gut microbiota showed that compared to MOD group, Bifidobacterium was increased, but Proteobacteria, Helicobacter and Parasutterella were decreased in INU group. Helicobacter was decreased in MET group. Correlation analysis showed that gut microbiota was correlated with inflammatory factors. Our results revealed that inulin and metformin alleviated PCOS via anti-inflammation and modulating gut microbiota, which may contribute to potential clinical therapy for the disease.

Inulin-Type Fructan Supplementation of 3- to 6-Year-Old Children Is Associated with Higher Fecal Bifidobacterium Concentrations and Fewer Febrile Episodes Requiring Medical Attention.

Background: Inulin-type fructans used in formula have been shown to promote microbiota composition and stool consistency closer to those of breastfed infants and to have beneficial effects on fever occurrence, diarrhea, and incidence of infections requiring antibiotic treatment in infants. Objectives: The primary study aim was to explore whether prophylactic supplementation with prebiotic fructans is able to influence the frequency of infectious diseases in kindergarten children during a winter period. A secondary objective was to ascertain the effect on the intestinal microbiota. Methods: 142 boys and 128 girls aged 3-6 y were randomly allocated to consume 6 g/d fructans or maltodextrin for 24 wk. At baseline, stool samples were collected for microbiota analysis and anthropometric measurements were made. During the intervention period diagnoses were recorded by physicians, whereas disease symptoms, kindergarten absenteeism, dietary habits, and stool consistency were recorded by parents. Baseline measurements were repeated at wk 24. Results: In total 219 children finished the study. Both the relative abundance of Bifidobacterium (P < 0.001) and that of Lactobacillus (P = 0.014) were 19.9% and 7.8% higher, respectively, post data normalization, in stool samples of children receiving fructans as compared with those of controls at wk 24. This was accompanied by significantly softer stools within the normal range in the prebiotic group from wk 12 onwards. The incidence of febrile episodes requiring medical attention [0.65 ± 1.09 compared with 0.9 ± 1.11 infections/(24 wk × child), P = 0.04] and that of sinusitis (0.01 ± 0.1 compared with 0.06 ± 0.25, P = 0.03) were significantly lower in the prebiotic group. The number of infectious episodes and their duration reported by parents did not differ significantly between the 2 intervention groups. Conclusions: Prebiotic supplementation modified the composition of the intestinal microbiota and resulted in softer stools in kindergarten-aged children. The reduction in febrile episodes requiring medical attention supports the concept of further studies on prebiotics in young children. This trial was registered at clinicaltrials.gov as NCT03241355.

Effects of prebiotic inulin-type fructans on blood metabolite and hormone concentrations and faecal microbiota and metabolites in overweight dogs.

Because obesity is associated with many co-morbidities, including diabetes mellitus, this study evaluated the second-meal effect of a commercial prebiotic, inulin-type fructans, and the effects of the prebiotic on faecal microbiota, metabolites and bile acids (BA). Nine overweight beagles were used in a replicated 3×3 Latin square design to test a non-prebiotic control (cellulose) against a low (equivalent to 0·5 % diet) and high dose (equivalent to 1·0 % diet) of prebiotic over 14-d treatments. All dogs were fed the same diet twice daily, with treatments provided orally via gelatin capsules before meals. On days 13 or 14 of each period, fresh faecal samples were collected, dogs were fed at 08.00 hours and then challenged with 1 g/kg body weight of maltodextrin in place of the 16.00 hours meal. Repeated blood samples were analysed for glucose and hormone concentrations to determine postprandial incremental AUC (IAUC) data. Baseline glucose, insulin and active glucagon-like peptide-1 levels were similar between all groups (P>0·10). Glucose and insulin IAUC after glucose challenge appeared lower following the high dose, but did not reach statistical relevance. Prebiotic intervention resulted in an increase in relative abundance of some Firmicutes and a decrease in the relative abundance of some Proteobacteria. Individual and total faecal SCFA were significantly increased (P<0·05) following prebiotic supplementation. Total concentration of excreted faecal BA tended to increase in dogs fed the prebiotic (P=0·06). Our results indicate that higher doses of inulin-type prebiotics may serve as modulators of gut microbiota, metabolites and BA pool in overweight dogs.

Replacement of glycaemic carbohydrates by inulin-type fructans from chicory (oligofructose, inulin) reduces the postprandial blood glucose and insulin response to foods: report of two double-blind, randomized, controlled trials.

PURPOSE: Inulin-type fructans are recognized as prebiotic dietary fibres and classified as non-digestible carbohydrates that do not contribute to glycaemia. The aim of the present studies was to investigate the glycaemic response (GR) and insulinaemic response (IR) to foods in which sucrose was partially replaced by inulin or oligofructose from chicory. METHODS: In a double-blind, randomized, controlled cross-over design, 40-42 healthy adults consumed a yogurt drink containing oligofructose or fruit jelly containing inulin and the respective full-sugar variants. Capillary blood glucose and insulin were measured in fasted participants and at 15, 30, 45, 60, 90, and 120 min after starting to drink/eat. For each test food, the incremental area under the curve (iAUC) for glucose and insulin was calculated and the GR and IR determined. RESULTS: Consumption of a yogurt drink with oligofructose which was 20% reduced in sugars significantly lowered the glycaemic response compared to the full-sugar reference (iAUC120min 31.9 and 37.3 mmol/L/min, respectively; p < 0.05). A fruit jelly made with inulin and containing 30% less sugars than the full-sugar variant likewise resulted in a significantly reduced blood glucose response (iAUC120min 53.7 and 63.7 mmol/L/min, respectively; p < 0.05). In both studies, the postprandial insulin response was lowered in parallel (p < 0.05). The reduction of postprandial glycaemia was positively correlated to the proportion of sugars replaced by inulin-type fructans (p < 0.001). CONCLUSIONS: In conclusion, the studies confirmed that substitution of glycaemic sugars by inulin or oligofructose from chicory may be an effective strategy to reduce the postprandial blood glucose response to foods.

Prebiotic inulin-type fructans induce specific changes in the human gut microbiota.

OBJECTIVE: Contrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterisation of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (gas chromatography mass spectrometry) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and faecal metabolites profiles. DESIGN: Faecal samples collected during a double-blind, randomised, cross-over intervention study set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analysed. Faecal microbiota composition and metabolite profiles were linked to the study's clinical outcome as well as to quality-of-life measurements recorded. RESULTS: While faecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition and specific inulin-induced changes in relative abundances of Anaerostipes, Bilophila and Bifidobacterium were identified. The observed decrease in Bilophila abundances following inulin consumption was associated with both softer stools and a favourable change in constipation-specific quality-of-life measures. CONCLUSIONS: Ecosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated with three genera, one of which (Bilophila) representing a promising novel target for mechanistic research. TRIAL REGISTRATION NUMBER: NCT02548247.

Modulation of rotavirus severe gastroenteritis by the combination of probiotics and prebiotics.

Annual mortality rates due to infectious diarrhea are about 2.2 million; children are the most vulnerable age group to severe gastroenteritis, representing group A rotaviruses as the main cause of disease. One of the main factors of rotavirus pathogenesis is the NSP4 protein, which has been characterized as a viral toxin involved in triggering several cellular responses leading to diarrhea. Furthermore, the rotavirus protein NSP1 has been associated with interferon production inhibition by inducing the degradation of interferon regulatory factors IRF3, IRF5, and IRF7. On the other hand, probiotics such as Bifidobacterium and Lactobacillus species in combination with prebiotics such as inulin, HMO, scGOS, lcFOS have been associated with improved generalized antiviral response and anti-rotavirus effect by the reduction of rotavirus infectivity and viral shedding, decreased expression of NSP4 and increased levels of specific anti-rotavirus IgAs. Moreover, these probiotics and prebiotics have been related to shorter duration and severity of rotavirus diarrhea, to the prevention of infection and reduced incidence of reinfections. In this review we will discuss in detail about the rotavirus pathogenesis and immunity, and how probiotics such as Lactobacillus and Bifidobacterium species in combination with prebiotics have been associated with the prevention or modulation of rotavirus severe gastroenteritis.

Effect of Butyrate and Inulin Supplementation on Glycemic Status, Lipid Profile and Glucagon-Like Peptide 1 Level in Patients with Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Trial.

Studies on humans with diabetes mellitus showed that the crosstalk between the intestinal microbiota and the host has a key role in controlling the disease. The aim of this study was to evaluate the effects of sodium butyrate and high performance inulin supplementation simultaneously or singly on glycemic status, lipid profile, and glucagon-like peptide 1 level in adults with type 2 diabetes mellitus. Sixty patients were recruited for the study. The participants were randomly allocated, using randomized block procedure, to one of the four treatment groups (A, B, C, or D). Group A received sodium butyrate capsules, group B received inulin supplement powder, group C was exposed to the concomitant use of inulin and sodium butyrate, and group D consumed placebo for 45 consecutive days. Markers of glycemia, lipid profile, and glucagon-like peptide 1 were measured pre- and post-intervention. Dietary supplementation in groups A, B, and C significantly reduced diastolic blood pressure in comparison with the placebo group (p<0.05). Also, intra-group statistical analysis showed that only treatment with sodium butyrate + inulin (group C) significantly reduced fasting blood sugar (p=0.049) and waist to hip ratio (p=0.020). Waist circumference in groups B and C reduced significantly after the intervention (p=0.007 and p=0.011; respectively). The post hoc Tukey tests showed significant increase in glucagon-like peptide 1 concentration in groups A and C in comparison with group D (p<0.05). The results suggest that inulin supplementation may be useful to diabetic patients and these effects could be increased with butyrate supplement.

Effect of Chicory-derived Inulin on Abdominal Sensations and Bowel Motor Function.

GOAL: To determine the effect of a prebiotic chicory-derived inulin-type fructan on the tolerance of intestinal gas. BACKGROUND: Subjects with gas-related complaints exhibit impaired handling of intestinal gas loads and we hypothesized that inulin would have a beneficial effect. STUDY: Placebo-controlled, parallel, randomized, double-blind trial. Subjects with abdominal symptoms and reduced tolerance of intestinal gas (selected by a pretest) received either inulin (8 g/d, n=18) or maltodextrin as a placebo (8 g/d, n=18) for 4 weeks. A gas challenge test (4 h jejunal gas infusion at 12 mL/min while measuring abdominal symptoms and gas retention for 3 h) was performed before and at the end of the intervention phase. Gastrointestinal symptoms and bowel habits (using daily questionnaires for 1 wk) and fecal bifidobacteria counts were measured before and at the end of the intervention. RESULTS: Inulin decreased gas retention during the gas challenge test (by 22%; P=0.035 vs. baseline), while the placebo did not, but the intergroup difference was not statistically significant (P=0.343). Inulin and placebo reduced the perception of abdominal sensations in the gas challenge test to a similar extent (by 52% and 43%, respectively). Participants reported moderate gastrointestinal symptoms and normal bowel habits during baseline examination, and these findings remained unchanged in both groups during the intervention. Inulin led to a higher relative abundance of bifidobacteria counts (P=0.01 vs. placebo). CONCLUSIONS: A daily dose of inulin that promotes bifidobacteria growth and may improve gut function, is well tolerated by subjects with gastrointestinal complaints.

Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial.

Constipation is among the most common health impairments in Western countries. This study aimed to determine the effect of the chicory-derived fermentable dietary fiber Orafti® Inulin on stool frequency in healthy subjects with constipation. The study was conducted according to recent guidance documents for investigating bowel function and used a randomized, double-blind, placebo-controlled, cross-over design with a 2-week wash-out phase. Each study period comprised a run-in phase followed by 4 weeks daily intake of 3 × 4g inulin or maltodextrin (placebo). Forty-four healthy volunteers with constipation documented stool frequency and consistency, gastrointestinal characteristics and quality of life. Consumption of Orafti® Inulin significantly increased stool frequency compared to placebo (median 4.0 [IQR 2.5-4.5] versus 3.0 [IQR 2.5-4.0] stools/week, p = 0.038). This was accompanied by a softening of stools and trend toward higher satisfaction versus placebo (p = 0.059). In conclusion, Orafti® Inulin was effective in volunteers with chronic constipation and significantly improved bowel function. CLINICAL TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT02548247.