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.

Inulin-based formulations as an emerging therapeutic strategy for cancer: A comprehensive review.

Cancer stands as the second leading cause of death in the United States (US). Most chemotherapeutic agents exhibit severe adverse effects that are attributed to exposure of drugs to off-target tissues, posing a significant challenge in cancer therapy management. In recent years, inulin, a naturally occurring prebiotic fiber has gained substantial attention for its potential in cancer treatment owing to its multitudinous health values. Its distinctive structure, stability, and nutritional properties position it as an effective adjuvant and carrier for drug delivery in cancer therapy. To address some of the above unmet clinical issues, this review summarizes the recent efforts towards the development of inulin-based nanomaterials and nanocomposites for healthcare applications with special emphasis on the multifunctional role of inulin in cancer therapy as a synergist, signaling molecule, immunomodulatory and anticarcinogenic molecule. Furthermore, the review provides a concise overview of ongoing clinical trials and observational studies associated with inulin-based therapy. In conclusion, the current review offers insights on the significant role of inulin interventions in exploring its potential as a therapeutic agent to treat cancer.

Dietary supplementation with low and high polymerization inulin ameliorates adipose tissue inflammation via the TLR4/NF-κB pathway mediated by gut microbiota disturbance in obese dogs.

Inflammation induced by gut microbiota disorder plays an important role in promoting obesity. Inulin has beneficial effects on gut microflora and metabolic endotoxaemia. However, the chain length of inulin determines its different physiological effects. This study aimed to investigate the effect of low polymerization inulin (LPI) and high polymerization inulin (HPI) on inflammation in dogs with obesity induced by a high-fat diet and its potential mechanism. HPI, relative to LPI, significantly reduced the concentrations of LPS, IL-6 and TNF-α in serum and downregulated both the mRNA and protein expression of TLR4, NF-κB, TNF-α and IL-6 in adipose tissue. HPI and LPI intervention reduced adipose tissue fatty accumulation, which improved obesity. Supplementation with LPI and HPI increased gut microbiota diversity and altered specific bacterial populations at both the phylum and genus levels. The relative abundances of Prevotella, Fusobacterium and Enterobacter, which were positively correlated with the serum concentrations of LPS, IL-6 and TNF-α, were reduced. Our results demonstrate that both LPI and HPI can be used as an effective strategy for reducing inflammation and regulating gut microbiota, which can ameliorate obesity in dogs. Moreover, HPI exerts more positive regulation of the inflammatory response and gut microbiota dysfunction than LPI.

The Comparative Effects of Inulin and Bacillus clausii on LPS-Induced Endotoxemic Rat Liver.

BACKGROUND: This paper sought to investigate the modifies of inulin and Bacillus clausii on the lipopolysaccharides (LPS) inducing oxidative stress signaling pathway in the endotoxemic rat model. METHODS: Wistar albino male rats (n = 36), divided into six groups, were formed randomly in the following stages: the control group; the prebiotic group (Inulin; 500 mg/kg); the probiotic group (Bacillus clausii; 1x109 CFU); the LPS group (1.5 mg/kg) as the endotoxemic model; the prebiotic group + LPS; and the probiotic group + LPS as treatment groups. RESULTS: The reactive oxygen species (ROS), advanced oxidation products of protein (AOPP), thiobarbituric acid reactive substances (TBARS), total oxidant status (TOS), oxidative stress index (OSI), and myeloperoxidase activity (MPO) levels increased in LPS-induced toxicity. Prebiotic treatment decreased LPS-induced hepatotoxicity on rat liver as observed in the decrease in the levels of oxidative stress parameters, such as ROS, TBARS, TOS, and OSI. The effect of the probiotic treatment on the ROS, AOPP, TOS, OSI levels was not statistically significant. However, it was determined that probiotic application was effective in the TBARS, TAS, and GSH levels. When the biochemical results of the prebiotic and probiotic treatment applications were compared, it was found that the prebiotic treatment was more effective on oxidative stress parameters (ROS, TBARS, TOS, and OSI). In addition, the histological damage score and MPO-staining results of the prebiotic treatment group were found to be more effective than the probiotic group. CONCLUSION: In this first study, where inulin and Bacillus clausii spores are used against liver damage caused by LPS, inulin provides much more effective protection than Bacillus clausii spores.

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.

Targeted therapeutic effects of oral inulin-modified double-layered nanoparticles containing chemotherapeutics on orthotopic colon cancer.

Colon cancer is emerging as one of the most prevalent cancers globally. Oral colonic drug delivery systems have attracted considerable attention in the treatment of orthotopic colon cancer due to their superior properties. However, the particularity and complexity of the gastrointestinal structure are a hindrance to the safe delivery of drugs to the target site of the colon tumor. Herein, to achieve an effective delivery system specifically targeting the colon, we designed paclitaxel (PTX)-loaded oral colon double-targeted nanoparticles using polylactic acid-polyethyleneimine (PLA-PEI) and hyaluronic acid-inulin (HA-IN). IN is enzyme sensitive and hardly degraded in the upper digestive tract; as such, it can ensure the safe delivery of nanoparticles to the colon. The "IN shell" is degraded by colon-specific bacteria at the colon site. The exposed HA not only promotes intestinal mucosal crossing of nanoparticles, but also acts as the target of CD44 and plays an active targeting role in tumor tissues. The action of the proton sponge effect of PEI induces the successful release of the nanoparticle. The prepared nanoparticles have a negative charge of -19.5 ± 1.2 mV and a size of 176.7 ± 0.3 nm with a narrow PDI of 0.148 ± 0.004. C26 cells were used for in vitro anticancer studies, including fluorescence staining and flow cytometry, and to explore inhibition of proliferation. The analysis demonstrated that the nanoparticles were more efficiently taken up by cancer cells, exhibiting greater cytotoxicity and apoptosis-inducing ability compared to free drugs. Moreover, in vivo studies revealed that the nanoparticles could remain in vivo for 24 h and accumulate at the tumor site. These data provide evidence of the therapeutic effect on orthotopic colon cancer. Also, safety evaluation results demonstrated that PLA-PEI/HA-IN is a safe drug delivery vector, therefore, holds great promise as a new therapeutic strategy for orthotopic colon cancer treatment.

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..

Dietary Supplementation of Inulin Ameliorates Subclinical Mastitis via Regulation of Rumen Microbial Community and Metabolites in Dairy Cows.

Subclinical mastitis (SCM) is one of the highly infectious diseases in dairy cows with the characteristics of high incidence and nonvisible clinical symptoms. The gastrointestinal microbiota is closely related to mastitis. Inulin is a prebiotic fiber with functions in improving intestinal microbial communities and enhancing the host's immunity. However, the impact of dietary inulin on the rumen inner environment remains unknown. The current study investigated whether inulin could relieve SCM by affecting the profiles of ruminal bacterial and metabolites in dairy cows. Inulin inclusion rates were 0, 100, 200, 300, and 400 g/day per cow, respectively. Inulin increased milk yield, milk protein, and lactose and reduced the somatic cell counts (SCC) in milk. In serum, the concentration of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and malondialdehyde (MDA) were decreased, and IL-4 and superoxide dismutase (SOD) were increased. Meanwhile, inulin increased the concentration of propionate, butyrate, and lactic acid (LA), while it decreased NH3-N in rumen. The propionate- and butyrate-producing bacteria (e.g., Prevotella and Butyrivibrio) and several beneficial commensal bacteria (e.g., Muribaculaceae and Bifidobacterium) as well as metabolites related to energy and amino acid metabolism (e.g., melibiose and l-glutamate) were increased. However, several proinflammatory bacteria (e.g., Clostridia UCG-014, Streptococcus, and Escherichia-Shigella) were decreased, accompanied by the downregulation of lipid proinflammatory metabolites, for example, ceramide(d18:0/15:0) [Cer(d18:0/15:0)] and 17-phenyl-18,19,20-trinor-prostaglandin E2. In the current study, the above indicators showed the best response in the 300 g/day inulin group. Overall, dietary supplementation of inulin could alleviate inflammatory responses in cows with SCM through improving the rumen inner environment. IMPORTANCE The correlation between mastitis and the gastrointestinal microbiome in dairy cows has been demonstrated. Regulating the profile of rumen microorganisms may contribute to remission of subclinical mastitis (SCM). Supplementation of inulin in the diets of cows with SCM could increase the abundance of short-chain fatty acid (SCFA)-producing bacteria and beneficial commensal bacteria in rumen and meanwhile the levels of amino acids and energy metabolism. Conversely, the abundance of ruminal bacteria and metabolites with proinflammatory effects were decreased. Our study suggests that the improvement of the rumen internal environment by inulin supplementation could ameliorate inflammatory responses during SCM in dairy cows and thus improve lactation performance and milk quality. Our results provide a theoretical basis for regulation measures of SCM in dairy cows.

Probiotic-prebiotic-synbiotic modulation of (YAP1, LATS1 and NF2 mRNAs/miR-1205/lncRNA SRD5A3-AS1) panel in NASH animal model.

AIM: To investigate the prophylactic efficacy of gut microbiota-based treatments on nonalcoholic steatohepatitis (NASH) management via modulation of Hippo signaling pathway-related genes (YAP1, LATS1 and NF2), and their epigenetic regulators (miR-1205 and lncRNA SRD5A3-AS1) retrieved from in-silico data analysis. MATERIALS & METHODS: Histopathological, biochemical, molecular and immunohistochemistry analyses were used to assess the effects of multistrain probiotic mixture and prebiotic inulin fiber on high sucrose high fat (HSHF) diet-induced NASH in rats. These treatments were administered orally either alone or in combination, along with HSHF diet. RESULTS: Both probiotic mixture and prebiotic inulin fiber attenuated steatosis, inflammation and fibrosis grades in HSHF diet-induced NASH rats. Moreover, the applied treatments significantly prevented the elevation of serum liver enzymes and improved lipid panel. At the molecular level, both treatments down-regulated hepatic YAP1 mRNA and miR-1205 expressions, and concomitantly up-regulated the expression of hepatic LATS1& NF2 mRNAs and the lncRNA SRD5A3-AS1. At the protein level, both treatments decreased the hepatic content of the inflammatory marker IL6 and the fibrotic marker TGFß1. Moreover, an observable reduction in α-SMA together with noticeable elevation in LATS1/2 protein expression levels were detected in liver sections compared to the untreated rats. CONCLUSION: Probiotic mixture and prebiotic inulin fiber, either alone or in combination, attenuated NASH progression and ameliorated both fibrosis and hepatic inflammation in the applied animal model. The produced effect was correlated with modulation of the retrieved (YAP1, LATS1 and NF2) - (miR-1205) - (lncRNA SRD5A3-AS1) RNA panel.

Prebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth.

Growing evidence supports the importance of gut microbiota in the control of tumor growth and response to therapy. Here, we select prebiotics that can enrich bacterial taxa that promote anti-tumor immunity. Addition of the prebiotics inulin or mucin to the diet of C57BL/6 mice induces anti-tumor immune responses and inhibition of BRAF mutant melanoma growth in a subcutaneously implanted syngeneic mouse model. Mucin fails to inhibit tumor growth in germ-free mice, indicating that the gut microbiota is required for the activation of the anti-tumor immune response. Inulin and mucin drive distinct changes in the microbiota, as inulin, but not mucin, limits tumor growth in syngeneic mouse models of colon cancer and NRAS mutant melanoma and enhances the efficacy of a MEK inhibitor against melanoma while delaying the emergence of drug resistance. We highlight the importance of gut microbiota in anti-tumor immunity and the potential therapeutic role for prebiotics in this process.

Inulin Supplementation Reduces Systolic Blood Pressure in Women with Breast Cancer Undergoing Neoadjuvant Chemotherapy.

INTRODUCTION: Breast cancer is the most frequently diagnosed malignancy in women, and comorbidities like hypertension and obesity diminish their quality of life and negatively affect their response to chemotherapy. Furthermore, inulin supplementation is associated with the reduction of cardiovascular diseases (CVD) risk. OBJECTIVE: To determine whether inulin supplementation prevents the elevation of blood pressure in women with breast cancer undergoing neoadjuvant therapy with cyclophosphamide and doxorubicin. METHODS: This was a randomized, double-blind placebo controlled trial which included women with early-stage breast cancer undergoing neoadjuvant therapy (n=38). Patients were randomly assigned to participate in two different groups to receive either 15 g of inulin or 15 g of placebo (maltodextrin) for 21 days. Body composition and blood pressure were evaluated before and after the supplementation period. RESULTS: Women in the inulin group showed a lower systolic blood pressure (SBP) after the supplementation (-4.21 mmHg, p<0.001). However, SBP increased in the placebo supplemented group. Diastolic blood pressure (DBP) nonsignificantly decreased in the inulin group. Inulin supplementation also increased BMI (p<0.001) but reduced BFP (p=0.288). Furthermore, confounding variables, such as BMI, baseline fasting glucose, age, menopause status, vomiting, constipation, and chronic medication did not have a statistical influence over the inulin effect on SBP. CONCLUSION: Inulin supplementation reduces SBP and prevents increases in DBP in women with breast cancer. This could be an innovative nutraceutical approach to prevent hypertension present in women with this type of cancer at an early stage and may improve the quality of life of the patients and their prognostic development through chemotherapy. TRIAL REGISTRATION NUMBER: This trial is registered with ACTRN12616001532493.

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.

N-acetyl cysteine, inulin and the two as a combined therapy ameliorate cognitive decline in testosterone-deprived rats.

Our previous studies reported that testosterone-deprived rats developed cognitive decline as a result of increased brain oxidative stress, microglia hyperactivity, and hippocampal dysplasticity. In addition, gut dysbiosis occurred in these rats. Previous studies demonstrated that n-acetyl cysteine (NAC) and a prebiotic (inulin) improved cognition in several pathological conditions. However, its effects on cognition in the testosterone-deprived condition have never been investigated. This study hypothesized that the administration of NAC, inulin, and a combined therapy improved cognition in castrated rats. Here we report that metabolic disturbance was not observed in the ORX rats, but gut dysbiosis was found in these rats. ORX rats developed blood-brain-barrier (BBB) breakdown, and increased brain oxidative stress as indicated by increased hippocampal production of reactive oxygen species (ROS) and an increase in brain malondialdehyde level. ORX rats also demonstrated glia hyperactivation, resulting in hippocampal apoptosis, hippocampal dysplasticity, and cognitive decline. All treatments equally ameliorated cognitive decline by improving gut dysbiosis, alleviating BBB dysfunction, decreasing hippocampal ROS production, decreasing hippocampal apoptosis, and reducing microglia and astrocyte activity. These findings suggest that NAC, inulin, and the combined therapy ameliorated the deleterious effects on the brain in castrated male rats similar to those treated with testosterone.

Protective effect of inulin on methotrexate- induced liver toxicity in mice.

Methotrexate (MTX) is an effectively used drug in the treatment of cancer and inflammatory diseases but, its use is related with hepatotoxicity. Inulin with antioxidant properties has hepatoprotective effects. In this research, we assessed inulin effects on MTX-induced liver toxicity. 48 male mice were randomly assigned into 6 equal groups. Mice were Pre-treatment with inulin (100, 200 and 400 mg/kg) for 9 consecutive days, orally) and MTX (10 mg/kg, intraperitoneally) was received on the 7th, to 9th day. Blood and liver were collected to assess liver functional test in serum samples and Stress oxidative biomarkers, pathological changes, the expressions levels of apoptotic factors, such as, Bcl-2, caspase -3 and miR-122 in the mice liver. The results indicated that MTX administration induced marked liver damage and serums factors of all of the mice. Furthermore, there was a decrease in the Bcl2 and an increase in the caspase-3 activity and miR-122 expression compared to the control group. Instead, inulin Pre-treatment clearly improved these variations induced by MTX. Finally, our results revealed the new evidence that the hepatoprotective effects of inulin might be mediated via the modulations of apoptotic and oxidative stress factors.

Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health.

Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43. Rather, HFD decimates gut microbiota, resulting in loss of enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI), and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, interleukin-22 (IL-22) production, enterocyte proliferation, and antimicrobial gene expression in a microbiota-dependent manner, as assessed by antibiotic and germ-free approaches. Inulin-induced IL-22 expression, which required innate lymphoid cells, prevented microbiota encroachment and protected against LGI and metabolic syndrome. Thus, fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function.

Odd-chain fatty acids as a biomarker for dietary fiber intake: a novel pathway for endogenous production from propionate.

Background: The risk of type 2 diabetes is inversely correlated with plasma concentrations of odd-chain fatty acids [OCFAs; pentadecanoic acid (15:0) and heptadecanoic acid (17:0)], which are considered as biomarkers for dairy fat intake in humans. However, rodent studies suggest that OCFAs are synthesized endogenously from gut-derived propionate. Propionate increases with dietary fiber consumption and has been shown to improve insulin sensitivity.Objective: We hypothesized that OCFAs are produced in humans from dietary fibers by a novel endogenous pathway.Design: In a randomized, double-blind crossover study, 16 healthy individuals were supplemented with cellulose (30 g/d), inulin (30 g/d), or propionate (6 g/d) for 7 d. In addition, human hepatoma cells were incubated with different propionate concentrations. OCFAs were determined in plasma phospholipids and hepatoma cells by gas chromatography.Results: Cellulose did not affect plasma OCFA levels, whereas inulin and propionate increased pentadecanoic acid by ∼17% (P < 0.05) and 13% (P = 0.05), respectively. The effect on heptadecanoic acid was even more pronounced, because it was elevated in almost all participants by inulin (11%; P < 0.01) and propionate (13%; P < 0.001). Furthermore, cell culture experiments showed a positive association between propionate and OCFA levels (R2 = 0.99, P < 0.0001), whereas palmitate (16:0) was negatively correlated (R2 = 0.83, P = 0.004).Conclusions: Our data show that gut-derived propionate is used for the hepatic synthesis of OCFAs in humans. The association of OCFAs with a decreased risk of type 2 diabetes may therefore also relate to dietary fiber intake and not only dairy fat. This trial was registered at www.germanctr.de as DRKS00010121.

Novel Combination of Prebiotics Galacto-Oligosaccharides and Inulin-Inhibited Aberrant Crypt Foci Formation and Biomarkers of Colon Cancer in Wistar Rats.

The selectivity and beneficial effects of prebiotics are mainly dependent on composition and glycosidic linkage among monosaccharide units. This is the first study to use prebiotic galacto-oligosaccharides (GOS) that contains ß-1,6 and ß-1,3 glycosidic linkages and the novel combination of GOS and inulin in cancer prevention. The objective of the present study is to explore the role of novel GOS and inulin against various biomarkers of colorectal cancer (CRC) and the incidence of aberrant crypt foci (ACF) in a 1,2-dimethyl hydrazine dihydrochloride (DMH)-induced rodent model. Prebiotic treatments of combined GOS and inulin (57 mg each), as well as individual doses (GOS: 76-151 mg; inulin 114 mg), were given to DMH-treated animals for 16 weeks. Our data reveal the significant preventive effect of the GOS and inulin combination against the development of CRC. It was observed that inhibition of ACF formation (55.8%) was significantly (p ≤ 0.05) higher using the GOS and inulin combination than GOS (41.4%) and inulin (51.2%) treatments alone. This combination also rendered better results on short-chain fatty acids (SCFA) and bacterial enzymatic activities. Dose-dependent effects of prebiotic treatments were also observed on cecum and fecal bacterial enzymes and on SCFA. Thus, this study demonstrated that novel combination of GOS and inulin exhibited stronger preventive activity than their individual treatments alone, and can be a promising strategy for CRC chemoprevention.

Hydrophobically modified inulin as an amphiphilic carbohydrate polymer for micellar delivery of paclitaxel for intravenous route.

Micellization offers several advantages for the delivery of water insoluble drugs including a nanoparticulate 'core-shell' delivery system for drug targeting. Recently, hydrophobically modified polysaccharides (HMPs) are gaining recognition as micelle forming polymers to encapsulate hydrophobic drugs. In this manuscript, for the first time, we have evaluated the self-assembling properties of a lauryl carbamate derivative of the poly-fructose natural polymer inulin (Inutec SP1(®) (INT)) to form paclitaxel (PTX) loaded micelles. INT self-assembled into well-defined micellar structures in aqueous environment with a low critical micellar concentration of 27.8 µg/ml. INT micelles exhibited excellent hemocompatibility and low toxicity to cultured cells. PTX loaded INT micelles exhibited a mean size of 256.37 ± 10.45 nm with excellent drug encapsulation efficiency (95.66 ± 2.25%) and loading (8.69 ± 0.22%). PTX loaded micelles also displayed sustained release of PTX and enhanced anti-cancer efficacy in-vitro in mouse melanoma cells (B16F10) compared to Taxol formulation with Cremophor EL as solvent. In addition, PTX loaded INT micelles exhibited comparable in-vivo antitumor activity in B16F10 allograft mouse model at half the dose of Taxol. In conclusion, INT offers safe, inexpensive and natural alternative to widely used PEG-modified polymers for the formulation of micellar delivery systems for paclitaxel.

Preventive use of Lactobacillus plantarum LS/07 and inulin to relieve symptoms of acute colitis.

The aim of presented study was to investigate the influence of Lactobacillus plantarum LS/07 and inulin on the activity of ß-glucuronidase enzyme, and counts of coliform and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8), and trancription nuclear factor kappa beta (NFκB) activities in colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. The rats were randomly divided into four groups - CG, AC, AC+PRE and AC+PRO. Colitis was induced using of 5% DSS in drinking water for 7d. DSS application increased activity of ß-glucuronidase (P < 0.001), increased counts of coliforms, and decreased lactobacilli counts (P < 0.05) in comparison to control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFκB activities showed increased expression in acute colitis group. Inulin diet modified counts of microorganims and decreased ß-glucuronidase activity, suppressed NFκB activities (P < 0.001) and down regulate synthesis of IL-6 (P < 0.01) in serum and colon tissue and tissue IL-8 (P < 0.05). Lactobacillus plantarum LS/07 decreased ß-glucuronidase activity (P < 0.05), levels of IL-6 and IL-8 (P < 0.001). These results were consistent with the addition of histological findings. Our results indicate that dietary intake of Lactobacillus plantarum LS/07 and inulin suppressed expression observed markers, which play an important role in the inflammatory process, which predisposes their use in prevention or treatment of acute colitis.

Effects of prebiotic supplementation on the expression of proteins regulating iron absorption in anaemic growing rats.

Prebiotics may increase intestinal Fe absorption in anaemic growing rats. The present study evaluated the effects of high-performance (HP) inulin and oligofructose on factors that regulate Fe absorption in anaemic rats during the growth phase. Male Wistar rats aged 21 d of age were fed AIN-93G ration without Fe for 2 weeks to induce Fe-deficiency anaemia. The rats were fed on day 35 a control diet, or a diet with 10 % HP inulin, or a diet with 10 % oligofructose, without Fe supplementation. The animals were euthanised after 2 weeks, and segments of the duodenum, caecum, colon and liver were removed. The expression levels of proteins in the intestinal segments were assessed using Western blotting. The levels of serum, urine and liver hepcidin and the concentrations of IL-10, IL-6 and TNF-α in the caecum, colon and liver were measured using the ELISA test. HP inulin increased the expression of the divalent metal transporter 1 protein in the caecum by 162 % (P= 0·04), and the expression of duodenal cytochrome b reductase in the colon by 136 % (P= 0·02). Oligofructose decreased the expression of the protein ferroportin in the duodenum (P= 0·02), the concentrations of IL-10 (P= 0·044), IL-6 (P= 0·036) and TNF-α (P= 0·004) in the caecum, as well as the level of urinary hepcidin (P< 0·001). These results indicate that prebiotics may interfere with the expression of various intestinal proteins and systemic factors involved in the regulation of intestinal Fe absorption in anaemic rats during the growth phase.