Pomegranate Juice Supplemented with Inulin Modulates Gut Microbiota and Promotes the Production of Microbiota-Associated Metabolites in Overweight/Obese Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial.

Pomegranate juice (PJ) and inulin have been reported to ameliorate diet-induced metabolic disorders by regulating gut microbiota dysbiosis. However, there was a lack of clinical evidence for the combined effects of PJ and inulin on regulating gut microbiota in individuals with metabolic disorders. A double-blind, parallel, randomized, placebo-controlled trial was conducted, and 68 overweight/obese individuals (25 ≤ BMI ≤ 35 kg/m2) were randomly assigned to receive 200 mL/d PJ, PJ supplemented with inulin, or placebo for 3 weeks. Our results showed that PJ and PJ+inulin did not significantly alter the levels of anthropometric and blood biochemical indicators after 3 weeks of treatment. However, there was an increasingly significant impact from placebo to PJ to PJ+inulin on the composition of gut microbiota. Detailed bacterial abundance analysis further showed that PJ+inulin treatment more profoundly resulted in significant changes in the abundance of gut microbiota at each taxonomic level than PJ. Moreover, PJ+inulin treatment also promoted the production of microbiota-associated short-chain fatty acids and pomegranate polyphenol metabolites, which correlated with the abundance of the bacterial genus. Our results suggested that PJ supplemented with inulin modulates gut microbiota composition and thus promotes the production of microbiota-associated metabolites that exert potential beneficial effects in overweight/obese subjects.

The genomes of Dahlia pinnata, Cosmos bipinnatus, and Bidens alba in tribe Coreopsideae provide insights into polyploid evolution and inulin biosynthesis.

BACKGROUND: The Coreopsideae tribe, a subset of the Asteraceae family, encompasses economically vital genera like Dahlia, Cosmos, and Bidens, which are widely employed in medicine, horticulture, ecology, and food applications. Nevertheless, the lack of reference genomes hinders evolutionary and biological investigations in this tribe. RESULTS: Here, we present 3 haplotype-resolved chromosome-level reference genomes of the tribe Coreopsideae, including 2 popular flowering plants (Dahlia pinnata and Cosmos bipinnatus) and 1 invasive weed plant (Bidens alba), with assembled genome sizes 3.93 G, 1.02 G, and 1.87 G, respectively. We found that Gypsy transposable elements contribute mostly to the larger genome size of D. pinnata, and multiple chromosome rearrangements have occurred in tribe Coreopsideae. Besides the shared whole-genome duplication (WGD-2) in the Heliantheae alliance, our analyses showed that D. pinnata and B. alba each underwent an independent recent WGD-3 event: in D. pinnata, it is more likely to be a self-WGD, while in B. alba, it is from the hybridization of 2 ancestor species. Further, we identified key genes in the inulin metabolic pathway and found that the pseudogenization of 1-FEH1 and 1-FEH2 genes in D. pinnata and the deletion of 3 key residues of 1-FFT proteins in C. bipinnatus and B. alba may probably explain why D. pinnata produces much more inulin than the other 2 plants. CONCLUSIONS: Collectively, the genomic resources for the Coreopsideae tribe will promote phylogenomics in Asteraceae plants, facilitate ornamental molecular breeding improvements and inulin production, and help prevent invasive weeds.

The emergence of inflammatory microglia during gut inflammation is not affected by FFAR2 expression in intestinal epithelial cells or peripheral myeloid cells.

Gut inflammation can trigger neuroinflammation and is linked to mood disorders. Microbiota-derived short-chain fatty acids (SCFAs) can modulate microglia, yet the mechanism remains elusive. Since microglia do not express free-fatty acid receptor (FFAR)2, but intestinal epithelial cells (IEC) and peripheral myeloid cells do, we hypothesized that SCFA-mediated FFAR2 activation within the gut or peripheral myeloid cells may impact microglia inflammation. To test this hypothesis, we developed a tamoxifen-inducible conditional knockout mouse model targeting FFAR2 exclusively on IEC and induced intestinal inflammation with dextran sodium sulfate (DSS), a well-established colitis model. Given FFAR2's high expression in myeloid cells, we also investigated its role by selectively deleting it in these populations of cells. In an initial study, male and female wild-type mice received 0 or 2% DSS for 5d and microglia were isolated 3d later to assess inflammatory status. DSS induced intestinal inflammation and upregulated inflammatory gene expression in microglia, indicating inflammatory signaling via the gut-brain axis. Despite the lack of significant effects of sex in the intestinal phenotype, male mice showed higher microglial inflammatory response than females. Subsequent studies using FFAR2 knockout models revealed that FFAR2 expression in IECs or immune myeloid cells did not affect DSS-induced colonic pathology (i.e. clinical and histological scores and colon length), or colonic expression of inflammatory genes. However, FFAR2 knockout led to an upregulation of several microglial inflammatory genes in control mice and downregulation in DSS-treated mice, suggesting that FFAR2 may constrain neuroinflammatory gene expression under healthy homeostatic conditions but may permit it during intestinal inflammation. No interactions with sex were observed, suggesting sex does not play a role on FFAR2 potential function in gut-brain communication in the context of colitis. To evaluate the role of FFAR2 activated by microbiota-derived SCFAs, we employed the same knockout and DSS models adding fermentable dietary fiber (0 or 2.5% inulin for 8 wks). Despite no genotype or fiber main effects, contrary to our hypothesis, inulin feeding augmented DSS-induced inflammation and signs of colitis, suggesting context-dependent effects of fiber. These findings highlight microglial involvement in colitis-associated neuroinflammation and advance our understanding of FFAR2's role in the gut-brain axis. Although not integral, we observed that the role of FFAR2 differs between homeostatic and inflammatory conditions, underscoring the need to consider different inflammatory conditions and disease contexts when investigating the role of FFAR2 and SCFAs in the gut-brain axis.

An inulin-type fructan CP-A from Codonopsis pilosula attenuates experimental colitis in mice by promoting autophagy-mediated inactivation of NLRP3 inflammasome.

Inulin-type fructan CP-A, a predominant polysaccharide in Codonopsis pilosula, demonstrates regulatory effects on immune activity and anti-inflammation. The efficacy of CP-A in treating ulcerative colitis (UC) is, however, not well-established. This study employed an in vitro lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) and an in vivo dextran sulfate sodium (DSS)-induced colitis mouse model to explore CP-A's protective effects against experimental colitis and its underlying mechanisms. We monitored the clinical symptoms in mice using various parameters: body weight, disease activity index (DAI), colon length, spleen weight, and histopathological scores. Additionally, molecular markers were assessed through enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays. Results showed that CP-A significantly reduced reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6, IL-1ß, IL-18) in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1, ZO-1, and occludin proteins in NCM460 cells. Correspondingly, in vivo findings revealed that CP-A administration markedly improved DAI, reduced colon shortening, and decreased the production of myeloperoxidase (MPO), malondialdehyde (MDA), ROS, IL-1ß, IL-18, and NOD-like receptor protein 3 (NLRP3) inflammasome-associated genes/proteins in UC mice. CP-A treatment also elevated glutathione (GSH) and superoxide dismutase (SOD) levels, stimulated autophagy (LC3B, P62, Beclin-1, and ATG5), and reinforced Claudin-1 and ZO-1 expression, thereby aiding in intestinal epithelial barrier repair in colitis mice. Notably, the inhibition of autophagy via chloroquine (CQ) diminished CP-A's protective impact against colitis in vivo. These findings elucidate that CP-A's therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagy-mediated NLRP3 inflammasome inactivation. Consequently, inulin-type fructan CP-A emerges as a promising drug candidate for UC treatment.

Exploring the Role of Inulin in Targeting the Gut Microbiota: An Innovative Strategy for Alleviating Colonic Fibrosis Induced By Irradiation.

The use of radiation therapy to treat pelvic and abdominal cancers can lead to the development of either acute or chronic radiation enteropathy. Radiation-induced chronic colonic fibrosis is a common gastrointestinal disorder resulting from the above radiation therapy. In this study, we establish the efficacy of inulin supplements in safeguarding against colonic fibrosis caused by irradiation therapy. Studies have demonstrated that inulin supplements enhance the proliferation of bacteria responsible to produce short-chain fatty acids (SCFAs) and elevate the levels of SCFAs in feces. In a mouse model of chronic radiation enteropathy, the transplantation of gut microbiota and its metabolites from feces of inulin-treated mice were found to reduce colonic fibrosis in validation experiments. Administering inulin-derived metabolites from gut microbiota led to a notable decrease in the expression of genes linked to fibrosis and collagen production in mouse embryonic fibroblast cell line NIH/3T3. In the cell line, inulin-derived metabolites also suppressed the expression of genes linked to the extracellular matrix synthesis pathway. The results indicate a novel and practical approach to safeguarding against chronic radiation-induced colonic fibrosis.

Effects of Oat ß-Glucan and Inulin on Alleviation of Nonalcoholic Steatohepatitis Aggravated by Circadian Disruption in C57BL/6J Mice.

This was the first study that examined the effects of oat ß-glucan and inulin on diet-induced nonalcoholic steatohepatitis (NASH) in circadian-disrupted (CD)-male C57BL/6J mice. CD intensified NASH, significantly increasing alanine aminotransferase and upregulating hepatic tumor necrosis factor α (TNFα) and transforming growth factor ß 1 (TGFß1). However, these observations were significantly alleviated by oat ß-glucan and inulin treatments. Compared to CD NASH mice, oat ß-glucan significantly decreased the liver index, aspartate aminotransferase (AST), and insulin. In prebiotic-treated and CD NASH mice, significant negative correlations were found between enrichment of Muribaculaceae bacterium Isolate-036 (Harlan), Muribaculaceae bacterium Isolate-001 (NCI), and Bacteroides ovatus after oat ß-glucan supplementation with TNFα and TGFß1 levels; and enrichment of Muribaculaceae bacterium Isolate-110 (HZI) after inulin supplementation with AST level. In conclusion, oat ß-glucan and inulin exhibited similar antiliver injury, anti-inflammatory, and antifibrotic activities but had no effect on cecal short-chain fatty acids and gut microbiota diversity in CD NASH mice.

Haplotype-resolved chromosome-level genome of hexaploid Jerusalem artichoke provides insights into its origin, evolution, and inulin metabolism.

Jerusalem artichoke (Helianthus tuberosus) is a global multifunctional crop. It has wide applications in the food, health, feed, and biofuel industries and in ecological protection; it also serves as a germplasm pool for breeding of the global oil crop common sunflower (Helianthus annuus). However, biological studies of Jerusalem artichoke have been hindered by a lack of genome sequences, and its high polyploidy and large genome size have posed challenges to genome assembly. Here, we report a 21-Gb chromosome-level assembly of the hexaploid Jerusalem artichoke genome, which comprises 17 homologous groups, each with 6 pseudochromosomes. We found multiple large-scale chromosome rearrangements between Jerusalem artichoke and common sunflower, and our results show that the hexaploid genome of Jerusalem artichoke was formed by a hybridization event between a tetraploid and a diploid Helianthus species, followed by chromosome doubling of the hybrid, which occurred approximately 2 million years ago. Moreover, we identified more copies of actively expressed genes involved in inulin metabolism and showed that these genes may still be undergoing loss of function or sub- or neofunctionalization. These genomic resources will promote further biological studies, breeding improvement, and industrial utilization of Helianthus crops.

Inulin-like polysaccharide ABWW may impede CCl4 induced hepatic stellate cell activation through mediating the FAK/PI3K/AKT signaling pathway in vitro & in vivo.

Studies have shown that terrestrial acidic polysaccharides containing carboxyl groups and seaweed sulfated polysaccharides have strong potential in anti-liver fibrosis. However, there is no investigation on the anti-liver fibrosis of fructan, a ubiquitous natural polysaccharide. The present study aimed to understand the effect of fructan in ameliorating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Here, an inulin-like fructan ABWW from Achyranthes bidentata Bl. was characterized by fructose enzymatic hydrolysis, methylation analysis, ESI-MS, and NMR. It was composed of →2)-ß-d-Fruf-(1→ and →2)-ß-d-Fruf-(1, 6→, terminated with →1)-α-d-Glcp and →2)-ß-d-Fruf residues. The biological studies showed that ABWW could improve liver damage and liver fibrosis induced by CCl4in vivo and inhibit hepatic stellate cell (HSC) activation and migration in vitro. We further demonstrated that ABWW inhibited LX2 activation via suppressing the FAK/PI3K/AKT signaling pathway. Hence, ABWW might be a potential novel active compound for anti-fibrosis new drug development.

The preventive effects of inulin, cellulose, and their mixture on colorectal cancer liver metastasis in mice by regulating gut microbiota.

Many studies have found that dietary fiber can protect against colorectal cancer (CRC). Survival in CRC patients is significantly reduced due to metastasis. However, little is known regarding the impact of dietary fiber on the CRC metastasis. In this study, we analyzed the effects of inulin, cellulose, and their mixture on CRC metastasis in a murine orthotopic transplantation model. BALB/C male mice were divided into the normal control (NC) (AIN-93 M diet), MOD (AIN-93 M diet), INU (10% w/w inulin), CEL (10% w/w cellulose), and MIX (5% w/w inulin + 5% w/w cellulose) groups. Dietary fiber intake inhibited the weights of the orthotopic tumors, liver weights, and liver metastasis area (p < 0.05) and improved the survival rate of tumor-bearing mice. Compared to the NC, the expression of ß-catenin and the epithelial marker E-cadherin were lower, and that of mesenchymal markers, such as N-cadherin, MMP-9, and VEGF, were higher in the MOD group. All inulin, cellulose, and their mixture restored the gut microbiota diversity, and they, respectively, increased the relative abundance of Bifidobacteriales, Lactobacillus, and Lachnospiraceae. Inulin restored the levels of acetic acid, propionic acid, isobutyric acid, and butyric acid. Spearman correlation analysis results showed that there was a positive correlation between five genera and six short-chain fatty acids (SCFAs) (adjusted p < 0.05). In conclusion, all inulin, cellulose, and their mixture have inhibitory effects on CRC metastasis, which may be achieved by the regulation of gut microbiota, the production of SCFAs, and the inhibition of the epithelial-to-mesenchymal transition process. Among the three dietary fiber intervention groups, the inhibitory effect of inulin is more significant.

Dietary Supplementation of Inulin Contributes to the Prevention of Estrogen Receptor-Negative Mammary Cancer by Alteration of Gut Microbial Communities and Epigenetic Regulations.

Breast cancer (BC) is among the most frequently diagnosed malignant cancers in women in the United States. Diet and nutrition supplementation are closely related to BC onset and progression, and inulin is commercially available as a health supplement to improve gut health. However, little is known with respect to inulin intake for BC prevention. We investigated the effect of an inulin-supplemented diet on the prevention of estrogen receptor-negative mammary carcinoma in a transgenic mouse model. Plasma short-chain fatty acids were measured, the gut microbial composition was analyzed, and the expression of proteins related to cell cycle and epigenetics-related genes was measured. Inulin supplementation greatly inhibited tumor growth and significantly delayed tumor latency. The mice that consumed inulin had a distinct microbiome and higher diversity of gut microbial composition compared to the control. The concentration of propionic acid in plasma was significantly higher in the inulin-supplemented group. The protein expression of epigenetic-modulating histone deacetylase 2 (Hdac2), Hdac8, and DNA methyltransferase 3b decreased. The protein expression of factors related to tumor cell proliferation and survival, such as Akt, phospho-PI3K, and NF-kB, also decreased with inulin administration. Furthermore, sodium propionate showed BC prevention effect in vivo through epigenetic regulations. These studies suggest that modulating microbial composition through inulin consumption may be a promising strategy for BC prevention.

Inulin: properties and health benefits.

Inulin, a soluble dietary fiber, is widely found in more than 36 000 plant species as a reserve polysaccharide. The primary sources of inulin, include Jerusalem artichoke, chicory, onion, garlic, barley, and dahlia, among which Jerusalem artichoke tubers and chicory roots are often used as raw materials for inulin production in the food industry. It is universally acknowledged that inulin as a prebiotic has an outstanding effect on the regulation of intestinal microbiota via stimulating the growth of beneficial bacteria. In addition, inulin also exhibits excellent health benefits in regulating lipid metabolism, weight loss, lowering blood sugar, inhibiting the expression of inflammatory factors, reducing the risk of colon cancer, enhancing mineral absorption, improving constipation, and relieving depression. In this review paper, we attempt to present an exhaustive overview of the function and health benefits of inulin.

Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids.

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.

Safety Evaluation of Goat Milk Added with the Prebiotic Inulin Fermented with the Potentially Probiotic Native Culture Limosilactobacillus mucosae CNPC007 in Co-culture with Streptococcus thermophilus QGE: Analysis of Acute and Repeated Dose Oral Toxicity.

Despite functional goat milk products having emerged due to their importance for human nutrition and health, few studies have assessed the safety of consumption of goat dairy products containing potentially probiotic autochthonous lactic acid bacteria supplemented with prebiotic carbohydrates. Aiming this field, this study evaluated the safety of goat's milk fermented with Streptococcus thermophilus QGE, the autochthonous Limosilactobacillus mucosae CNPC007 culture, and the prebiotic inulin, through single- and repeated-dose oral toxicity tests (SDT and RDT, respectively) in animals. Ten female Swiss Webster mice were used for SDT evaluation - 2 groups, SDTc (20 mL/kg of filtered water) and SDTt (20 mL/kg of fermented milk) - and 40 Wistar rats for RDT - RDT3, RDT6, and RDT12 (treated with fermented milk at doses of 3 mL/kg, 6 mL/kg, and 12 mL/kg, respectively) and also RDTc (12 mL/kg of filtered water). For SDT, no signs of mortality or toxicity were observed, and the animals maintained the expected weight gain and feed intake. The RDT trials did not show mortality or signs of toxicity, as well as no change in body weight and organs, in the hematological and biochemical parameters, and also in relation to morphology and histology. Since the fermented milk did not cause any toxic effect in the conditions evaluated, it can be said that its no-adverse effect level (NOAEL) was considered to be higher than 20 mL/kg/day. Thus, the fermented milk with L. mucosae CNPC007 and inulin was considered to be of low toxicity, safe for use in rodents, and allowed for use in further studies.

The genomes of chicory, endive, great burdock and yacon provide insights into Asteraceae palaeo-polyploidization history and plant inulin production.

Inulin is an important reserve polysaccharide in Asteraceae plants, and is also widely used as a sweetener, a source of dietary fibre and prebiotic. Nevertheless, a lack of genomic resources for inulin-producing plants has hindered extensive studies on inulin metabolism and regulation. Here, we present chromosome-level reference genomes for four inulin-producing plants: chicory (Cichorium intybus), endive (Cichorium endivia), great burdock (Arctium lappa) and yacon (Smallanthus sonchifolius), with assembled genome sizes of 1.28, 0.89, 1.73 and 2.72 Gb, respectively. We found that the chicory, endive and great burdock genomes were shaped by whole genome triplication (WGT-1), and the yacon genome was shaped by WGT-1 and two subsequent whole genome duplications (WGD-2 and WGD-3). A yacon unique whole genome duplication (WGD-3) occurred 5.6-5.8 million years ago. Our results also showed the genome size difference between chicory and endive is largely due to LTR retrotransposons, and rejected a previous hypothesis that chicory is an ancestor of endive. Furthermore, we identified fructan-active-enzyme and transcription-factor genes, and found there is one copy in chicory, endive and great burdock but two copies in yacon for most of these genes, except for the 1-FEH II gene which is significantly expanded in chicory. Interestingly, inulin synthesis genes 1-SST and 1-FFT are located close to each other, as are the degradation genes 1-FEH I and 1-FEH II. Finally, we predicted protein structures for 1-FFT genes to explore the mechanism determining inulin chain length.

Global, distinctive, and personal changes in molecular and microbial profiles by specific fibers in humans.

Dietary fibers act through the microbiome to improve cardiovascular health and prevent metabolic disorders and cancer. To understand the health benefits of dietary fiber supplementation, we investigated two popular purified fibers, arabinoxylan (AX) and long-chain inulin (LCI), and a mixture of five fibers. We present multiomic signatures of metabolomics, lipidomics, proteomics, metagenomics, a cytokine panel, and clinical measurements on healthy and insulin-resistant participants. Each fiber is associated with fiber-dependent biochemical and microbial responses. AX consumption associates with a significant reduction in LDL and an increase in bile acids, contributing to its observed cholesterol reduction. LCI is associated with an increase in Bifidobacterium. However, at the highest LCI dose, there is increased inflammation and elevation in the liver enzyme alanine aminotransferase. This study yields insights into the effects of fiber supplementation and the mechanisms behind fiber-induced cholesterol reduction, and it shows effects of individual, purified fibers on the microbiome.

Bioengineered Cystinotic Kidney Tubules Recapitulate a Nephropathic Phenotype.

Nephropathic cystinosis is a rare and severe disease caused by disruptions in the CTNS gene. Cystinosis is characterized by lysosomal cystine accumulation, vesicle trafficking impairment, oxidative stress, and apoptosis. Additionally, cystinotic patients exhibit weakening and leakage of the proximal tubular segment of the nephrons, leading to renal Fanconi syndrome and kidney failure early in life. Current in vitro cystinotic models cannot recapitulate all clinical features of the disease which limits their translational value. Therefore, the development of novel, complex in vitro models that better mimic the disease and exhibit characteristics not compatible with 2-dimensional cell culture is of crucial importance for novel therapies development. In this study, we developed a 3-dimensional bioengineered model of nephropathic cystinosis by culturing conditionally immortalized proximal tubule epithelial cells (ciPTECs) on hollow fiber membranes (HFM). Cystinotic kidney tubules showed lysosomal cystine accumulation, increased autophagy and vesicle trafficking deterioration, the impairment of several metabolic pathways, and the disruption of the epithelial monolayer tightness as compared to control kidney tubules. In particular, the loss of monolayer organization and leakage could be mimicked with the use of the cystinotic kidney tubules, which has not been possible before, using the standard 2-dimensional cell culture. Overall, bioengineered cystinotic kidney tubules recapitulate better the nephropathic phenotype at a molecular, structural, and functional proximal tubule level compared to 2-dimensional cell cultures.

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..

Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies.

OBJECTIVE: Health-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. DESIGN: A 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. RESULTS: Colonic 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. CONCLUSIONS: Psyllium 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.

Inulin as a functional ingredient and their applications in meat products.

Inulin, a fructan-type non-digestible carbohydrate, is a natural functional dietary fiber found in selected plants including chicory, garlic, onion, leeks and asparagus. Due to increasing popularity of inulin and rising awareness toward its low calorie value and prebiotic related health implications, consumers are becoming more conscious on consuming inulin incorporated foods. In this review, the scientific studies published in recent years regarding potential applications of inulin in meat products; and their effects on physicochemical and sensory properties, and health implications are discussed. Meat based functional foods with inulin can lead to enhance digestive health by reducing the risk of diseases like constipation, irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. Inulin can be an interesting prebiotic ingredient in healthier meat formulations, apart from being a fat replacer and dietary fiber enhancer.

Distinct fermentation of human milk oligosaccharides 3-FL and LNT2 and GOS/inulin by infant gut microbiota and impact on adhesion of Lactobacillus plantarum WCFS1 to gut epithelial cells.

Human milk oligosaccharides (hMOs) are unique bioactive components in human milk. 3-Fucosyllactose (3-FL) is an abundantly present hMO that can be produced in sufficient amounts to allow application in infant formula. Lacto-N-triaose II (LNT2) can be obtained by acid hydrolysis of lacto-N-neotetraose (LNnT). Both 3-FL and LNT2 have been shown to have health benefits, but their impact on infant microbiota composition and microbial metabolic products such as short-chain fatty acids (SCFAs) is unknown. To gain more insight in fermentability, we performed in vitro fermentation studies of 3-FL and LNT2 using pooled fecal microbiota from 12-week-old infants. The commonly investigated galacto-oligosaccharides (GOS)/inulin (9 : 1) served as control. Compared to GOS/inulin, we observed a delayed utilization of 3-FL, which was utilized at 60.3% after 36 h of fermentation, and induced the gradual production of acetic acid and lactic acid. 3-FL specifically enriched bacteria of Bacteroides and Enterococcus genus. LNT2 was fermented much faster. After 14 h of fermentation, 90.1% was already utilized, and production of acetic acid, succinic acid, lactic acid and butyric acid was observed. LNT2 specifically increased the abundance of Collinsella, as well as Bifidobacterium. The GOS present in the GOS/inulin mixture was completely fermented after 14 h, while for inulin, only low DP was rapidly utilized after 14 h. To determine whether the fermentation might lead to enhanced colonization of commensal bacteria to gut epithelial cells, we investigated adhesion of the commensal Lactobacillus plantarum WCFS1 to Caco-2 cells. The fermentation digesta of LNT2 collected after 14 h, 24 h, and 36 h, and GOS/inulin after 24 h of fermentation significantly increased the adhesion of L. plantarum WCFS1 to Caco-2 cells, while 3-FL had no such effect. Our findings illustrate that fermentation of hMOs is very structure-dependent and different from the commonly applied GOS/inulin, which might lead to differential potencies to stimulate adhesion of commensal cells to gut epithelium and consequent microbial colonization. This knowledge might contribute to the design of tailored infant formulas containing specific hMO molecules to meet the need of infants during the transition from breastfeeding to formula.