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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.

ObjectiveContrary 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.DesignFaecal 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.ResultsWhile 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.ConclusionsEcosystem-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 numberNCT02548247.

ObjectiveHealth-promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with IBS, limiting their intake. Our aim was to test if coadministering psyllium with inulin would reduce gas production.DesignA randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500 mL test drink containing either inulin 20 g, psyllium 20 g, inulin 20 g+ psyllium 20 g or dextrose 20 g (placebo). Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours. Faecal samples from a subset of the patients with IBS were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI.ResultsColonic gas rose steadily from 0 to 6 hours, with inulin causing the greatest rise, median (IQR) AUC(0–360 min) 3145 (848–6502) mL·min. This was significantly reduced with inulin and psyllium coadministration to 618 (62–2345) mL·min (p=0.02), not significantly different from placebo. Colonic volumes AUC(0–360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium coadministration (p=0.005). Breath hydrogen rose significantly from 120 min after inulin but not psyllium; coadministration of psyllium with inulin delayed and reduced the maximum increase, AUC(0–360 min) from 7230 (3255–17910) ppm·hour to 1035 (360–4320) ppm·hour, p=0.007.Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production.ConclusionsPsyllium reduced inulin-related gas production in patients with IBS but does not directly inhibit fermentation. Whether coadministration with psyllium increases the tolerability of prebiotics in IBS warrants further study.Trial registration number NCT03265002.

Whole-grain rye foods reduce appetite, insulin and sometimes glucose responses. Increased gut fermentation and plant protein may mediate the effect. The aims of the present study were to investigate whether the appetite-suppressing effects of whole-grain rye porridge could be enhanced by replacing part of the rye with fermented dietary fibre and plant protein, and to explore the role of gut fermentation on appetite and metabolic responses over 8 h. We conducted a randomised, cross-over study using two rye porridges (40 and 55 g), three 40-g rye porridges with addition of inulin:gluten (9:3; 6:6; 3:9 g) and a refined wheat bread control (55 g), served as part of complete breakfasts. A standardised lunch and an ad libitum dinner were served 4 and 8 h later, respectively. Appetite, breath hydrogen and methane, glucose, insulin and glucagon-like peptide-1 (GLP-1) responses were measured over 8 h. Twenty-one healthy men and women, aged 23–60 years, with BMI of 21–33 kg/m2 participated in this study. Before lunch, the 55-g rye porridges lowered hunger by 20 % and desire to eat by 22 % and increased fullness by 29 % compared with wheat bread (P<0·05). Breath hydrogen increased proportionally to dietary fibre content (P<0·05). Plasma glucose after lunch was 6 % lower after the 55-g rye porridges compared with wheat bread (P<0·05) and correlated to breath hydrogen (P<0·001). No differences were observed in ad libitum food intake, insulin or GLP-1. We conclude that no further increase in satiety was observed when replacing part of the rye with inulin and gluten compared with plain rye porridges.

The aim of the present study was to assess synbiotic (Lactobacillus casei + inulin) influence on oxidative stress parameters such as concentrations of malondialdehyde (MDA), hydrogen peroxide (H2O2), glutathione, and free sulfhydryl groups content. Experiments were carried out on healthy volunteers (n=32). The subjects were divided into women group (n=16) and men group (n=16) and randomly assigned to synbiotic and control groups. Blood samples were collected before synbiotic supplementation and after 7 wks, at the end of the study. The administration of synbiotic resulted in a significant decrease in MDA (p<0.01), H2O2 (p<0.01), and GSSG concentrations (p<0.05) as compared with the control groups and significant increase in the concentrations of GSHt (p<0.001), GSH (p<0.01), and -SH group content (p<0.05) versus control. Synbiotics containing L. casei plus inulin may have positive influence on selected oxidative stress markers.

Microglia play a vital role maintaining brain homeostasis but can also cause persistent neuroinflammation. Short-chain fatty acids (SCFAs) produced by the intestinal microbiota have been suggested to regulate microglia inflammation indirectly by signaling through the gut-brain axis or directly by reaching the brain. The present work evaluated the anti-inflammatory effects of SCFAs on lipopolysaccharide (LPS)-stimulated microglia from mice fed inulin, a soluble fiber that is fermented by intestinal microbiota to produce SCFAs in vivo, and SCFAs applied to primary microglia in vitro. Feeding mice inulin increased SCFAs in the cecum and in plasma collected from the hepatic portal vein. Microglia isolated from mice fed inulin and stimulated with LPS in vitro secreted less tumor necrosis factor α (TNF-α) compared to microglia from mice not given inulin. Additionally, when mice were fed inulin and injected i.p with LPS, the ex vivo secretion of TNF-α by isolated microglia was lower than that secreted by microglia from mice not fed inulin and injected with LPS. Similarly, in vitro treatment of primary microglia with acetate and butyrate either alone or in combination downregulated microglia cytokine production with the effects being additive. SCFAs reduced histone deacetylase activity and nuclear factor-κB nuclear translocation after LPS treatment in vitro. Whereas microglia expression of SCFA receptors Ffar2 or Ffar3 was not detected by single-cell RNA sequencing analysis, the SCFA transporters Mct1 and Mct4 were. Nevertheless, inhibiting monocarboxylate transporters on primary microglia did not interfere with the anti-inflammatory effects of SCFAs, suggesting that if SCFAs produced in the gut regulate microglia directly it is likely through an epigenetic mechanism following diffusion.

In recent years, research has focused on the use of dietary fibers and prebiotics, since many of these polysaccharides can be metabolized by intestinal microbiota, leading to the production of short-chain fatty acids. The metabolites of prebiotic fermentation also show anti-inflammatory and immunomodulatory capabilities, suggesting an interesting role in the treatment of several pathological conditions. Galacto-oligosaccharide and short- and long-chain fructans (Fructo-oligosaccharides and inulin) are the most studied prebiotics, even if other dietary compounds seem to show the same features. There is an increasing interest in dietary strategies to modulate microbiota. The aim of this review is to explore the mechanisms of action of prebiotics and their effects on the principal gastro-intestinal disorders in adults, with a special focus on Galacto-oligosaccharides, Fructo-oligosaccharides, lactulose and new emerging substances which currently have evidence of prebiotics effects, such as xilooligosaccharides, soybean oligosaccharides, isomaltooligosaccharides, lactobionic acid, resistant starch and polyphenols.

Fifteen per cent of higher plants accumulate fructans. Plant development, nutritional status and stress exposure all affect fructan metabolism, and while fructan biochemistry is well understood, knowledge of its regulation has remained fragmentary. Here, we have explored chicory (Cichorium intybus) hairy root cultures (HRCs) to study the regulation of fructan metabolism in sink tissues in response to environmental cues. In standard medium (SM), HRCs did not accumulate inulin. However, upon transfer to high-carbon (C)/low-nitrogen (N) medium, expression of sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan:fructan 1-fructosyltransferase (1-FFT) was strongly induced and inulin accumulated. Upon return to SM, inulin was degraded, together with a coordinate decline of 1-SST and 1-FFT expression. In HRCs, cold-induced expression of fructan 1-exohydrolases (1-FEH I and IIa) was similar to cold induction in taproots, even in the absence of accumulated inulin. For high-C/low-N induction of 1-SST and 1-FFT, and cold induction of 1-FEH I and IIa, the signaling pathways were addressed. While 1-SST and 1-FFT induction was similarly prevented by inhibitors of Ca²⁺ signaling, protein kinases and phosphatases, cold induction of 1-FEH I and IIa revealed distinct signaling pathways. In summary, this study has established chicory HRCs as a convenient experimental system with which to study the regulation of fructan active enzyme (FAZY) expression in heterotrophic cells.

The H2 breath test is ideal for orocaecal transit time (OCTT) measurement, as it is non-invasive and inexpensive. Indigestible substrates added to a test meal are metabolised by the colonic bacteria, resulting in the production of H2 which is detected in end-exhalation breath. However, the substrates themselves can alter the transit times in the gastrointestinal tract. The aim of the present study is to compare OCTT and gastric emptying (GE) when lactulose in liquid (L-L), solid lactulose (L-S) and solid inulin (IN-S) are added to a test meal, and subsequently, to examine if inulin alters GE. Firstly, ten male volunteers were tested on three occasions. Volunteers ate a pancake breakfast containing 100 mg of 13C-octanoic acid and either 12 g of L-L, 12 g of L-S or 12 g of IN-S in a randomised order. Secondly, seven male volunteers were tested twice with meals containing either 12 g of IN-S or no substrate (NO-S). L-L induced the shortest OCTT (85·3 (sd 42·8) min) compared with L-S (162·4 (sd 62·6) min) and inulin (292·4 (sd 66·7) min; P = 0·007). GE half-time and lag phase (L-L: 61 (sd 9); L-S: 57 (sd 10); IN-S: 52 (sd 10) min; P = 0·005) were also affected, with L-L being the slowest. Thirdly, inulin reduced GE lag and latency phases (P < 0·05) compared with NO-S. Lactulose accelerates OCTT but delays GE compared with inulin. Inulin accelerates the onset of stomach emptying, but it has no effect on GE half-time. For these reasons, inulin is the preferred substrate for the H2 breath test.

Arbuscular mycorrhizal fungi (AMF) and phosphate solubilizing bacteria (PSB) could interact synergistically because PSB solubilize sparingly available phosphorous compounds into orthophosphate that AMF can absorb and transport to the host plant. Little is known about the interactions between these two groups in terms of promoting Jerusalem artichoke, Helianthus tuberosus L., which is widely planted by farmers because of its high inulin content. Production depends mainly on synthetic fertilizers as source of plant nutrients. This study aimed to isolate and characterize PSB and investigate the effects of co-inoculation of AMF and PSB on plant performance and inulin accumulation. Isolate UDJA102x89-9, identified as Klebsiella variicola (KV), showed phosphate-solubilizing ability and produced high amounts of several organic acids in vitro and of indole-3-acetic acid (IAA). The experiment combined KV and two AMF species ( Glomus multisubtensum (GM) and Rhizophagus intraradices (RI)). Co-inoculation of KV with RI, in combination with rock phosphate, showed the largest increases in plant growth and tuber inulin content, compared both to an unfertilized and fertilized control. This result would reveal whether the phosphate solubilization and IAA property of the PSB in vitro played a significant role in changing plant growth and production, and the available P was subsequently taken up and transported to plant roots by AMF. The high combined effect may have the potential for use by farmers in the future as a biofertilizer for inulin production by Helianthus tuberosus L.