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ObjectiveTo investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.DesignTwelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.ResultsBoth IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose.ConclusionThese data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.

Aging can result in major changes in the composition and metabolic activities of bacterial populations in the gastrointestinal system and result in impaired function of the immune system. We assessed the efficacy of prebiotic Darmocare Pre® (Bonusan Besloten Vennootschap (BV), Numansdorp, The Netherlands) to evaluate whether the regular intake of this product can improve frailty criteria, functional status and response of the immune system in elderly people affected by the frailty syndrome. The study was a placebo-controlled, randomized, double blind design in sixty older participants aged 65 and over. The prebiotic product was composed of a mixture of inulin plus fructooligosaccharides and was compared with placebo (maltodextrin). Participants were randomized to a parallel group intervention of 13 weeks’ duration with a daily intake of Darmocare Pre® or placebo. Either prebiotic or placebo were administered after breakfast (between 9–10 a.m.) dissolved in a glass of water carefully stirred just before drinking. The primary outcome was to study the effect on frailty syndrome. The secondary outcomes were effect on functional and cognitive behavior and sleep quality. Moreover, we evaluated whether prebiotic administration alters blood parameters (haemogram and biochemical analysis). The overall rate of frailty was not significantly modified by Darmocare Pre® administration. Nevertheless, prebiotic administration compared with placebo significantly improved two frailty criteria, e.g., exhaustion and handgrip strength (p < 0.01 and p < 0.05, respectively). No significant effects were observed in functional and cognitive behavior or sleep quality. The use of novel therapeutic approaches influencing the gut microbiota–muscle–brain axis could be considered for treatment of the frailty syndrome.

Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti® Synergy 1; 16 g/d) or placebo (Glucidex® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium (P=0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium (P<0·001) and Faecalibacterium (P=0·010) and decreases in Coprococcus (P=0·010), Dorea (P=0·043) and Ruminococcus (Lachnospiraceae family) (P=0·032). This study demonstrates that those with HDF intakes have a greater gut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.

Background and objectives Gut dysbiosis that resulted from the alteration between host-microbe interaction might worsen obesity-induced systemic inflammation. Gut microbiota manipulation by supplementation of prebiotic inulin may reverse metabolic abnormalities and improve obesity. This study aimed to determine whether inulin supplementation improved intestinal microbiota and microbial functional pathways in children with obesity. Methods Children with obesity whose BMI above median + 2SDs were recruited to a randomized, double-blinded placebo-controlled study. The participants aged 7–15 years were assigned to inulin supplement extracted from Thai Jerusalem artichoke (intervention), maltodextrin (placebo), and dietary fiber advice groups. All participants received similar monthly conventional advice and follow-up for 6 months. Fecal samples were collected for gut microbiome analysis using 16S rRNA sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was performed to infer microbial functional pathways. Results One hundred and forty-three children with available taxonomic and functional pathway abundance profiles were evaluated. A significant increase in alpha-diversity was observed in the inulin group. Inulin supplementation substantially enhanced Bifidobacterium , Blautia , Megasphaera , and several butyrate-producing bacteria, including Agathobacter , Eubacterium coprostanoligenes , and Subdoligranulum , compared to the other groups. The inulin group showed a significant difference in functional pathways of proteasome and riboflavin metabolism. These changes correlated with clinical and metabolic outcomes exclusively in the inulin group. Conclusions Inulin supplementation significantly promoted gut bacterial diversity and improved gut microbiota dysbiosis in children with obesity. The modulation of functional pathways by inulin suggests its potential to establish beneficial interactions between the gut microbiota and host physiology. Inulin supplementation could be a strategic treatment to restore the balance of intestinal microbiota and regulate their functions in childhood obesity.

Background Modulating the gut microbiota with prebiotics is a promising strategy for managing metabolic diseases. However, the clinical effects on glycemic metabolism across different populations remain uncertain. In this study, we conducted a randomized, double-blind investigation to examine the impact of inulin and fructooligosaccharides (FOS) on glycemic metabolism in overweight/obese and healthy adults. Methods A total of 131 adults were included, with 44 receiving inulin, 43 receiving FOS, and 44 receiving placebo over a period of 4 weeks. Blood and fecal samples were collected before and after the intervention, and various metabolic parameters, gut microbiota composition, and metabolites were analyzed. Results Placebo had no effect on glycemic metabolism or gut microbiota. Inulin significantly reduced glucose levels at 1 h (Cohen’s d  = 0.71, p  = 0.041) and 2 h (Cohen’s d  = 0.73, p  = 0.028) during oral glucose tolerance test (OGTT), increased fasting insulin (Cohen’s d  = 0.70, p  = 0.008), and lowered homocysteine (HCY) levels (Cohen’s d  = 0.76, p  = 0.014) in overweight/obese individuals. These effects were not observed in healthy individuals. In contrast, although FOS significantly decreased HCY (Cohen’s d  = 0.72, p  = 0.023), it did not improve glycemic metrics in either group. Inulin also reduced the abundance of Ruminococcus by 72.0% (from 1.661% ± 1.501% to 0.465% ± 0.594%), positively correlating with improved glycemic outcomes. Propionate levels decreased significantly in both overweight/obese (Cohen’s d  = 0.89, p  = 0.014) and healthy participants (Cohen’s d  = 1.19, p  = 0.020) following inulin. Functional prediction of gut microbiota revealed upregulation of microbial folate and glutathione metabolism with inulin, and purine metabolism with FOS. Conclusions Practically, inulin may be more suitable for managing glycemic dysregulation in overweight or obese individuals, while FOS may be considered for HCY reduction in individuals with normal glycemic status. Such targeted use of prebiotics could complement existing dietary and pharmacologic strategies in personalized metabolic care. Trial registration number ChiCTR-IOR-17010574.

The purpose of the present study was to establish the prebiotic effect of a new xylo-oligosaccharide (XOS) and of an inulin-and-XOS mixture (INU–XOS) and to determine their effect on endotoxaemia (lipopolysaccharides (LPS)) and immune parameters. In this randomised, parallel, placebo-controlled, double-blind study, sixty healthy volunteers were randomly assigned to three groups, receiving either 5 g XOS, INU–XOS (3 g inulin +1 g XOS) or an equivalent weight of wheat maltodextrin (placebo) during 4 weeks. Faecal samples were collected to assess the effects of these products on microbiota, as well as SCFA composition, enzymatic activities and secretory IgA production. Circulating LPS was measured in plasma samples, and whole blood was incubated with LPS to measure cytokine expression. Consumption of XOS alone increased the faecal concentrations of Bifidobacterium and butyrate and activities of α-glucosidase and β-glucuronidase, while decreasing the concentrations of acetate and p-cresol. Consumption of XOS in combination with inulin did not decrease the concentrations of acetate and p-cresol, but increased in addition the faecal concentrations of total SCFA and propionate. Furthermore, consumption of XOS in combination with inulin decreased LPS concentrations in blood and attenuated LPS-induced increases in gene expression in IL-1β and LPS-induced decreases in gene expression in IL-13 in blood. In conclusion, consumption of XOS alone or in combination with inulin results in beneficial albeit different changes in the intestinal microbiome on a high-fat diet. In addition, consumption of XOS in combination with inulin attenuates the proinflammatory effects of a high-fat diet in the blood of healthy subjects.

BACKGROUNDFrailty significantly affects morbidity and mortality rates in the older population (age >65 years). Age-related degenerative diseases are influenced by the intestinal microbiota. However, limited research exists on alterations in the intestinal microbiota in frail older individuals, and the effectiveness of prebiotic intervention for treating frailty remains uncertain.OBJECTIVEWe sought to examine the biological characteristics of the intestinal microbiome in frail older individuals and assess changes in both frailty status and gut microbiota following intervention with a prebiotic blend consisting of inulin and oligofructose.METHODSThe study consisted of 3 components: an observational analysis with a sample size of 1,693, a cross-sectional analysis (n = 300), and a multicenter double-blind, randomized, placebo-controlled trial (n = 200). Body composition, commonly used scales, biochemical markers, intestinal microbiota, and metabolites were examined in 3 groups of older individuals (nonfrail, prefrail, and frail). Subsequently, changes in these indicators were reevaluated after a 3-month intervention using the prebiotic mixture for the prefrail and frail groups.RESULTSThe intervention utilizing a combination of prebiotics significantly improved frailty and renal function among the older population, leading to notable increases in protein levels, body fat percentage, walking speed, and grip strength. Additionally, it stimulated an elevation in gut probiotic count and induced alterations in microbial metabolite expression levels as well as corresponding metabolic pathways.CONCLUSIONSThe findings suggest a potential link between changes in the gut microbiota and frailty in older adults. Prebiotics have the potential to modify the gut microbiota and metabolome, resulting in improved frailty status and prevention of its occurrence.TRIAL REGISTRATIONClinicalTrials.gov NCT03995342.

This study was conducted to evaluate the effect of inulin on bowel symptoms, depression and quality of life in individuals with constipation-predominant irritable bowel syndrome. This study was designed as a randomized, single-blind, placebo-controlled clinical trial with a parallel design and a 1:1 allocation ratio. Individuals (n = 34) aged between 21 and 63 years with constipation-predominant IBS were included in the study. Individuals were randomly assigned to two groups: the prebiotic group (n = 17), which received a 50%/50% mixture of inulin/oligofructose (4.6 g twice daily, for a total daily dose of 9.2 g), and the placebo group (n = 17), which total received 9.2 g of maltodextrin per day. The intervention period was 8 weeks. Bristol Stool Scale, IBS-Visual Analogue Scale (IBS-VAS), IBS-Symptom Severity Score Scale (IBS-SSS), IBS-Quality of Life Scale (IBS-QoL) and Beck Depression Scale were administered to the participants at the beginning, 1st month and 2nd month. As a result, total IBS-QoL score increased in the prebiotic group (61.0 ± 19.4 to 77.4 ± 15.1; p < 0.006), whereas total IBS-SSS score decreased (267.3 ± 56.0 to 195.8 ± 59.0; p < 0.026). In the prebiotic group, significant improvement was observed in the IBS-VAS parameters of constipation status (2.2 ± 2.3 to 4.9 ± 2.5; p < 0.042 group×time ), psychological state (7 (2–10) to 9 (5–10); p < 0.006). It is thought that inulin may have beneficial effects on reducing symptom severity and frequency and on quality of life in individuals with IBS in whom constipation is predominant.

Background Patients admitted to the intensive care unit (ICU) often have gut colonization with pathogenic bacteria and such colonization is associated with increased risk for death and infection. We conducted a trial to determine whether a prebiotic would improve the gut microbiome to decrease gut pathogen colonization and decrease downstream risk for infection among newly admitted medical ICU patients with sepsis. Methods This was a randomized, double-blind, placebo-controlled trial of adults who were admitted to the medical ICU for sepsis and were receiving broad-spectrum antibiotics. Participants were randomized 1:1:1 to placebo, inulin 16 g/day, or inulin 32 g/day which were given for seven days. The trial primary outcome was a surrogate measure for gut colonization resistance, namely the within-individual change from ICU admission to Day 3 in the relative abundance of short chain fatty acid (SCFA)-producing bacteria based on rectal swabs. Additional outcomes sought to evaluate the impact of inulin on the gut microbiome and downstream clinical effects. Results Ninety participants were analyzed including 30 in each study group. There was no difference between study groups in the within-individual change in the relative abundance of SCFA-producing bacteria from ICU admission to ICU Day 3 (placebo: 0.0% change, IQR − 8·0% to + 7·4% vs. combined inulin: 0·0% change, IQR − 10·1% to + 4·8%; p  = 0·91). At end-of-treatment on ICU Day 7, inulin did not affect SCFA-producer levels, microbiome diversity, or rates of gut colonization with pathogenic bacteria. After 30 days of clinical follow-up, inulin did not affect rates of death or clinical, culture-proven infection. Patients who died or developed culture-proven infections had lower relative abundance of SCFA-producing bacteria at ICU admission compared to those who did not ( p  = 0·03). Conclusions Prebiotic fiber had minimal impact on the gut microbiome in the ICU and did not improve clinical outcomes. Trial registration Clinicaltrials.gov: NCT03865706. Keypoints Question Does prebiotic fiber alter the gut microbiome in the medical ICU to decrease gut pathogen colonization and decrease downstream risk for infection? Findings This randomized controlled trial found that prebiotic inulin at doses up to 32 grams/day did not alter the gut microbiome among adults admitted to the ICU with sepsis. Even at these high doses, inulin was well tolerated. The taxonomic composition of the gut microbiome, assessed using longitudinal rectal swabs and stool samples for up to thirty days of follow-up, was not substantively altered by inulin; also unchanged by inulin were fecal levels of short chain fatty acids, gut colonization with pathogenic bacteria including vancomycin-resistant Enterococcus and multidrug-resistant Gram-negative bacteria, and clinical outcomes including culture-proven infection or death. Meaning Pre- and probiotics may face significant challenges in the ICU. Improved understanding of the dynamic changes within the gut microbiome in the ICU may lead to more targeted therapies.

Background: Colonic fermentation of dietary fibre to short-chain fatty acids (SCFA) influences appetite hormone secretion in animals, but SCFA production is excessive in obese animals. This suggests there may be resistance to the effect of SCFA on appetite hormones in obesity. Objectives: To determine the effects of inulin (IN) and resistant starch (RS) on postprandial SCFA, and gut hormone (glucagon-like peptide (GLP-1), peptide–tyrosine–tyrosine (PYY) and ghrelin) responses in healthy overweight/obese (OWO) vs lean (LN) humans. Subjects/Methods: Overnight-fasted participants (13 OWO and 12 LN) consumed 300 ml water containing 75 g glucose (GLU) as control or 75 g GLU plus 24 g IN, or 28.2 g RS using a randomised, single-blind, cross-over design. Blood for appetite hormones and SCFA was collected at intervals over 6 h. A standard lunch was served 4 h after the test drink. Results: Relative to GLU, IN, but not RS, significantly increased SCFA areas under the curve (AUC) from 4–6 h (AUC 4–6 ). Neither IN nor RS affected GLP-1 or PYY-AUC 4–6 . Although neither IN nor RS reduced ghrelin-AUC 4–6 compared with GLU, ghrelin at 6 h after IN was significantly lower than that after GLU ( P <0.05). After IN, relative to GLU, the changes in SCFA-AUC 4–6 were negatively related to the changes in ghrelin-AUC 4–6 ( P =0.017). SCFA and hormone responses did not differ significantly between LN and OWO. Conclusions: Acute increases in colonic SCFA do not affect GLP-1 or PYY responses in LN or OWO subjects, but may reduce ghrelin. The results do not support the hypothesis that SCFA acutely stimulate PYY and GLP-1 secretion; however, a longer adaptation to increased colonic fermentation or a larger sample size may yield different results.