Fecal-adherent mucus is a non-invasive source of primary human MUC2 for structural and functional characterization in health and disease.

The O-glycoprotein Mucin-2 (MUC2) forms the protective colon mucus layer. While animal models have demonstrated the importance of Muc2, few studies have explored human MUC2 in similar depth. Recent studies have revealed that secreted MUC2 is bound to human feces. We hypothesized human fecal MUC2 (HF-MUC2) was accessible for purification and downstream structural and functional characterization. We tested this via histologic and quantitative imaging on human fecal sections; extraction from feces for proteomic and O-glycomic characterization; and functional studies via growth and metabolic assays in vitro. Quantitative imaging of solid fecal sections showed a continuous mucus layer of varying thickness along human fecal sections with barrier functions intact. Lectin profiling showed HF-MUC2 bound several lectins but was weak to absent for Ulex europaeus 1 (α1,2 fucose-binding) and Sambucus nigra agglutinin (α2,6 sialic acid-binding), and did not have obvious b1/b2 barrier layers. HF-MUC2 separated by electrophoresis showed high molecular weight glycoprotein bands (∼1-2 MDa). Proteomics and Western analysis confirmed the enrichment of MUC2 and potential MUC2-associated proteins in HF-MUC2 extracts. MUC2 O-glycomics revealed diverse fucosylation, moderate sialylation, and little sulfation versus porcine colonic MUC2 and murine fecal Muc2. O-glycans were functional and supported the growth of Bacteroides thetaiotaomicron (B. theta) and short-chain fatty acid (SCFA) production in vitro. MUC2 could be similarly analyzed from inflammatory bowel disease stools, which displayed an altered glycomic profile and differential growth and SCFA production by B. theta versus healthy samples. These studies describe a new non-invasive platform for human MUC2 characterization in health and disease.

Bioprocess optimization for food-grade cellulolytic enzyme production from sorghum waste in a novel solid-state fermentation bioreactor for enhanced apple juice clarification.

Transforming global agricultural waste into eco-friendly products like industrial enzymes through bioconversion can help address sustainability challenges aligning with the United Nations' Sustainable Development Goals. Present study explored the production of high-yield food-grade cellulolytic enzymes from Trichoderma reesei MTCC 4876, using a novel media formulation with a combination of waste sorghum grass and cottonseed oil cake (3:1). Optimization of physical and environmental parameters, along with the screening and optimization of media components, led to an upscaled process in a novel 6-L solid-state fermentation (SSF)-packed bed reactor (PBR) with a substrate loading of 200 g. Saturated forced aeration proved crucial, resulting in high fungal biomass (31.15 ± 0.63 mg glucosamine/gm dry fermented substrate) and high yield cellulase (20.64 ± 0.36 FPU/g-ds) and xylanase (16,186 ± 912 IU/g-ds) production at an optimal airflow rate of 0.75 LPM. The PBR exhibited higher productivity than shake flasks for all the enzyme systems. Microfiltration and ultrafiltration of the crude cellulolytic extract achieved 94% and 71% recovery, respectively, with 13.54 FPU/mL activity in the cellulolytic enzyme concentrate. The concentrate displayed stability across wide pH and temperature ranges, with a half-life of 24.5-h at 50 °C. The cellulase concentrate, validated for food-grade safety, complies with permissible limits for potential pathogens, heavy metals, mycotoxins, and pesticide residue. It significantly improved apple juice clarity (94.37 T%) by reducing turbidity (21%) and viscosity (99%) while increasing total reducing sugar release by 63% compared with untreated juice. The study also highlighted the potential use of lignin-rich fermented end residue for fuel pellets within permissible SOx emission limits, offering sustainable biorefinery prospects. Utilizing agro wastes in a controlled bioreactor environment underscores the potential for efficient large-scale cellulase production, enabling integration into food-grade applications and presenting economic benefits to fruit juice industries.

Xylitol biosynthesis enhancement by Candida tropicalis via medium, process parameter optimization, and co-substrate supplementation.

The present study examines the impact of nitrogen sources (yeast extract, ammonium sulfate peptone, ammonium nitrate, urea, and sodium nitrate), salt solution (0.5 g/L MgSO4, 0.5 g/L KH2PO4, 0.3 g/L CaCl2), trace elements solution (0.1 g/L CuSO4, 0.1 g/L FeSO4, 0.02 g/L MnCl2, 0.02 g/L ZnSO4), operational parameters (temperature, aeration, agitation, initial pH and xylose concentration) and co- substrate supplementation (glucose, fructose, maltose, sucrose, and glycerol) on xylitol biosynthesis by Candida tropicalis ATCC 13803 using synthetic xylose. The significant medium components were identified using the Plackett Burman design followed by central composite designs to obtain the optimal concentration for the critical medium components in shaker flasks. Subsequently, the effect of operational parameters was examined using the One Factor At a Time method, followed by the impact of five co-substrates on xylitol biosynthesis in a 1 L bioreactor. The optimal media components and process parameters are as follows: peptone: 12.68 g/L, yeast extract: 6.62 g/L, salt solution (0.5 g/L MgSO4, 0.5 g/L KH2PO4, and 0.3 g/L CaCl2): 1.23 X (0.62 g/L, 0.62 g/L, and 0.37 g/L respectively), temperature: 30 °C, pH: 6, agitation: 400 rpm, aeration: 1 vvm, and xylose: 50 g/L. Optimization studies resulted in xylitol yield and productivity of 0.71 ± 0.004 g/g and 1.48 ± 0.018 g/L/h, respectively. Glycerol supplementation (2 g/L) further improved xylitol yield (0.83 ± 0.009 g/g) and productivity (1.87 ± 0.020 g/L/h) by 1.66 and 3.12 folds, respectively, higher than the unoptimized conditions thus exhibiting the potential of C. tropicalis ATCC 13803 being used for commercial xylitol production.

Sustainable production of eicosapentaenoic acid-rich oil from microalgae: Towards an algal biorefinery.

Utilization of sustainable natural resources such as microalgae has been considered for the production of biofuels, aquaculture feed, high-value bioactives such as omega-3 fatty acids, carotenoids, etc. Eicosapentaenoic acid (EPA) is an omega-3 fatty acid present in fish oil, which is of physiological importance to both humans and fish. Marine microalgae are sustainable sources of lipid rich in EPA, and different species have been explored for the production of EPA as a single product. There has been a rising interest in the concept of a multi-product biorefinery, focusing on the maximum valorization of the algal biomass. Targeting one or more value-added compounds in a biorefinery scenario can improve the commercial viability of low-value products such as triglycerides for biofuel. This approach has been viewed by technologists and experts as a sustainable and economically feasible possibility for the large-scale production of microalgae for its potential applications in biodiesel and jet fuel production, nutraceuticals, animal and aquaculture feeds, etc. In this review paper, we describe the recent developments in the production of high-value EPA-rich oil from microalgae, emphasizing the upstream and downstream bioprocess techniques, and the advantages of considering an EPA-rich oil-based biorefinery.

Deletion of mucin 2 induces colitis with concomitant metabolic abnormalities in mice.

Patients with inflammatory bowel disease (IBD) are at increased risk of under-recognized metabolic comorbidities. Chronic intestinal inflammation in IBD along with changes to the gut microbiome leads to broader systemic effects. Despite the existence of multiple animal models to study colitis, limited studies have examined the metabolic abnormalities associated with these models. In this study, a spontaneous model of colitis (mucin 2 knock-out mouse, Muc2-/-) was used to investigate the impact of intestinal disease on metabolic dysfunction. Before the onset of severe colitis, such as rectal prolapse, Muc2-/- mice exhibited impaired glucose clearance. Defects were noted in the insulin signaling pathway corresponding with upregulated genes in lipid utilization pathways, increased mitochondrial number, and peroxisome proliferator-activated coactivator 1α (PGC-1α), a transcription factor central to energy metabolism regulation. Parallel to these metabolic alterations, Muc2-/- mice exhibited systemic inflammation and bacteremia. We further characterized the dysbiotic microbiome's predicted functional categories given its contributing role to the colitic phenotype in the Muc2-/- mice. In addition to less butyrate levels, we show an increased predisposition to lipid metabolism and lipid biosynthesis pathways in the microbiome associated with the host's altered metabolic state. This study establishes the Muc2-/- mouse model that develops spontaneous colitis, as an ideal model for studying early comorbid metabolic dysfunction. Clarification of the underlying etiology of two phenotypes in this model could unravel important clues regarding the treatment of metabolic comorbidities during colitis.NEW & NOTEWORTHY This study discloses the impaired systemic energy metabolism in a classic colitis murine model (Muc2-/- knock-out model). Investigating the interaction between colitis and metabolic disorders helps to extend our knowledge on deciphering inflammatory bowel disease-associated comorbidities and provides new insight into clinical treatment.

The effects of voluntary wheel running on neuroinflammatory status: Role of monocyte chemoattractant protein-1.

The health benefits of exercise and physical activity (PA) have been well researched and it is widely accepted that PA is crucial for maintaining health. One of the mechanisms by which exercise and PA exert their beneficial effects is through peripheral immune system adaptations. To date, very few studies have looked at the regulation of neuroimmune reactions in response to PA. We studied the effect of voluntary wheel running (VWR) on pro- and anti-inflammatory cytokine levels, patterns of glial cell activation and expression of immune receptors in the brains of female C57BL/6 mice. By using homozygous monocyte chemoattractant protein (MCP)-1 null mice, we investigated the role of this key immunoregulatory cytokine in mediating VWR-induced neuroinflammatory responses. We demonstrated that, compared to their sedentary counterparts, C57BL/6 mice exposed for seven weeks to VWR had increased levels of pro- and anti-inflammatory cytokines, markers of glial cell activation and a trend towards increased expression of toll-like receptor (TLR) 4 in the brain. Measurements of serum cytokines revealed that the alterations in brain cytokine levels could not be explained by the effects of PA on peripheral cytokine levels. We propose that the modified neuroimmune status observed in the VWR group represents an activated immune system, as opposed to a less activated immune system in the sedentary group. Since MCP-1 knockout mice displayed differing patterns of pro- and anti-inflammatory brain cytokine expression and glial activation when compared to their wild-type counterparts, we concluded that the effects of VWR on neuroimmune reactions may be modulated by MCP-1. These identified immunomodulatory effects of PA in the brain could contribute to the observed positive relationship between physically active lifestyles and a reduced risk for a number of neurodegenerative diseases that possess a significant neuroinflammatory component.

Oxygen uptake rate as a tool for on-line estimation of cell biomass and bed temperature in a novel solid-state fermentation bioreactor.

Direct measurement of cell biomass is difficult in a solid-state fermentation (SSF) process involving filamentous fungi since the mycelium and the solid substrate are often inseparable. However, respiratory data are rich in information for real-time monitoring of microbial biomass production. In this regard, a correlation was obtained between oxygen uptake rate (OUR) and biomass concentration (X) of Rhizopus oryzae MTCC 1987, during phytase production, in an intermittently mixed novel SSF bioreactor. To obtain the correlation, various models describing sigmoidal growth were tested, namely the logistic, Gompertz, Stannard, and Schnute models. Regression analysis of experimental results, at different operating conditions of inlet air flow rate and relative humidity suggested that OUR and X were correlated well by the logistic model (R2 > 0.90). To corroborate the use of respiratory data for on-line measurement of metabolic activity, OUR was related to metabolic heat generation rate (Rq), and the logistic model was found to satisfactorily correlate Rq and X as well. The model parameter, YQ/X, when substituted into a heat transfer design equation, along with the values of other parameters and operating variables, gave reliable estimates of bed temperature. The correlations developed in the present study, between respiratory activity and biomass concentration may be extended on to other SSF processes for further validation and real-time monitoring of cell biomass and bed temperature.

Dietary Lipid Type, Rather Than Total Number of Calories, Alters Outcomes of Enteric Infection in Mice.

Dietary lipids modulate immunity, yet the means by which specific fatty acids affect infectious disease susceptibility remains unclear. Deciphering lipid-induced immunity is critical to understanding the balance required for protecting against pathogens while avoiding chronic inflammatory diseases. To understand how specific lipids alter susceptibility to enteric infection, we fed mice isocaloric, high-fat diets composed of corn oil (rich in n-6 polyunsaturated fatty acids [n-6 PUFAs]), olive oil (rich in monounsaturated fatty acids), or milk fat (rich in saturated fatty acids) with or without fish oil (rich in n-3 PUFAs). After 5 weeks of dietary intervention, mice were challenged with Citrobacter rodentium, and pathological responses were assessed. Olive oil diets resulted in little colonic pathology associated with intestinal alkaline phosphatase, a mucosal defense factor that detoxifies lipopolysaccharide. In contrast, while both corn oil and milk fat diets resulted in inflammation-induced colonic damage, only milk fat induced compensatory protective responses, including short chain fatty acid production. Fish oil combined with milk fat, unlike unsaturated lipid diets, had a protective effect associated with intestinal alkaline phosphatase activity. Overall, these results reveal that dietary lipid type, independent of the total number of calories associated with the dietary lipid, influences the susceptibility to enteric damage and the benefits of fish oil during infection.

Excess Linoleic Acid Increases Collagen I/III Ratio and "Stiffens" the Heart Muscle Following High Fat Diets.

Controversy exists on the benefits versus harms of n-6 polyunsaturated fatty acids (n-6 PUFA). Although n-6 PUFA demonstrates anti-atherosclerotic properties, survival following cardiac remodeling may be compromised. We hypothesized that n-6 PUFA like linoleic acid (LA) or other downstream PUFAs like γ-linolenic acid or arachidonic acid alter the transforming growth factor-ß (TGFß)-collagen axis in the heart. Excess dietary LA increased the collagen I/III ratio in the mouse myocardium, leading to cardiac "stiffening" characterized by impaired transmitral flow indicative of early diastolic dysfunction within 5 weeks. In vitro, LA under TGFß1 stimulation increased collagen I and lysyl oxidase (LOX), the enzyme that cross-links soluble collagen resulting in deposited collagen. Overexpression of fatty acid desaturase 2 (fads2), which metabolizes LA to downstream PUFAs, reduced collagen deposits, LOX maturation, and activity with LA, whereas overexpressing fads1, unrelated to LA desaturation, did not. Furthermore, fads2 knockdown by RNAi elevated LOX activity and collagen deposits in fibroblasts with LA but not oleic acid, implying a buildup of LA for aggravating such pro-fibrotic effects. As direct incubation with γ-linolenic acid or arachidonic acid also attenuated collagen deposits and LOX activity, we concluded that LA itself, independent of other downstream PUFAs, promotes the pro-fibrotic effects of n-6 PUFA. Overall, these results attempt to reconcile opposing views of n-6 PUFA on the cardiovascular system and present evidence supporting a cardiac muscle-specific effect of n-6 PUFAs. Therefore, aggravation of the collagen I/III ratio and cardiac stiffening by excess n-6 PUFA represent a novel pathway of cardiac lipotoxicity caused by high n-6 PUFA diets.

Ablation of intestinal epithelial sialylation predisposes to acute and chronic intestinal inflammation in mice.

BACKGROUND & AIMS: Addition of sialic acids (sialylation) to glycoconjugates is a common capping step of glycosylation. Our study aims to determine the roles of the overall sialylation in intestinal mucosal homeostasis. METHODS: Mice with constitutive deletion of intestinal epithelial sialylation (IEC Slc35a1-/- mice) and mice with inducible deletion of sialylation in intestinal epithelium (TM-IEC Slc35a1-/- mice) were generated, which were used to determine the roles of overall sialylation in intestinal mucosal homeostasis by ex vivo and muti-omics studies. RESULTS: IEC Slc35a1-/- mice developed mild spontaneous microbiota-dependent colitis. Additionally, 30% of IEC Slc35a1-/- mice had spontaneous tumors in the rectum over the age of 12 months. TM-IEC Slc35a1-/- mice were highly susceptible to acute inflammation induced by 1% DSS vs controls. Loss of total sialylation was associated with reduced mucus thickness on fecal sections and within colon tissues. TM-IEC Slc35a1-/- mice showed altered microbiota with an increase in Clostridia disporicum, which is associated a global reduction in the abundance of at least 20 unique taxa; however, metabolomic analysis did not show any significant differences in short-chain fatty acid levels. Treatment with 5-fluorouracil (5-FU) led to more severe small intestine mucositis in the IEC Slc35a1-/- mice vs. WT littermates, which was associated with reduced Lgr5+ cell representation in small intestinal crypts in IEC Slc35a1-/-;Lgr5-GFP mice. CONCLUSIONS: Loss of overall sialylation impairs mucus stability and the stem cell niche leading to microbiota-dependent spontaneous colitis and tumorigenesis.

Diets rich in n-6 PUFA induce intestinal microbial dysbiosis in aged mice.

Controversies have emerged regarding the beneficial v. detrimental effects of dietary n-6 PUFA. The alteration of the intestinal microbiota, a phenomenon termed dysbiosis, occurs during several chronic inflammatory diseases, but has not been well studied in an aged population. With present 'Western' diets predominantly composed of n-6 PUFA, we hypothesised that PUFA-rich diets cause intestinal dysbiosis in an aged population. C57BL/6 mice (aged 2 years) were fed a high-fat (40% energy), isoenergetic and isonitrogenous diet composed of rapeseed oil, maize oil or maize oil supplemented with fish oil. We examined ileal microbiota using fluorescence in situ hybridisation and stained tissues by immunofluorescence for the presence of immune cells and oxidative stress. We observed that feeding high-fat diets rich in n-6 PUFA promoted bacterial overgrowth but depleted microbes from the Bacteroidetes and Firmicutes phyla. This corresponded with increased body mass and infiltration of macrophages and neutrophils. Fish oil supplementation (rich in long-chain n-3 PUFA like DHA and EPA) restored the microbiota and inflammatory cell infiltration and promoted regulatory T-cell recruitment. However, fish oil supplementation was associated with increased oxidative stress, evident by the increased presence of 4-hydroxynonenal, a product of lipid peroxidation. These results suggest that an n-6 PUFA-rich diet can cause dysbiosis and intestinal inflammation in aged mice. However, while fish oil supplementation on an n-6 PUFA diet reverses dysbiosis, the combination of n-6 and n-3 PUFA, like DHA/EPA, leads to increased oxidative stress, which could exacerbate gastrointestinal disorders in the elderly.

Role of Bilateral Inferior Turbinoplasty as an Adjunct to Septoplasty in Improving Nasal Obstruction and Subjective Performance in Patients With Deviated Nasal Septum Associated With Allergic Rhinitis: An Interventional, Prospective Study.

BACKGROUND: Patients with nasal obstruction due to deviated nasal septum (DNS) often have allergic rhinitis (AR) as contributing factor. When optimal medical therapy for AR fails, septoplasty alone may not adequately treat nasal obstruction. Therefore, with bilateral inferior turbinate hypertrophy representing long-standing AR, adding bilateral inferior turbinoplasty (BIT) to septoplasty might be beneficial. OBJECTIVE: To assess whether septoplasty with/without BIT alleviates nasal obstruction in the above patient cohort and whether adding BIT to septoplasty brings significant benefit. METHODOLOGY: In this interventional, prospective study, patients with nasal obstruction due to DNS and persistent, moderate-severe AR refractory to optimal medication were randomly allocated into group A (septoplasty alone) and group B (septoplasty with BIT). Nasal Obstruction and Symptom Evaluation (NOSE) score, along with Subjective Performance parameters (days-off/month; number of outdoor visits/month; overall satisfaction score [OSS]) were used to assess the symptom and quality of life, respectively, at follow-up. RESULTS: Each group had 40 age/sex-matched patients. Friedman test, and subsequent pair-wise comparison within groups without Bonferroni correction, revealed that septoplasty with/without BIT elicited significant reduction in NOSE scores and in the Subjective Performance parameters (days-off/month; number of outdoor visits/month) at 3 and 6 months. Wilcoxon Signed Rank test revealed that the OSS within groups also improved significantly with time. Further, comparison between groups revealed significant improvement in NOSE scores at all levels of follow-up when BIT was included. However, there were no significant differences between groups in the Subjective Performance parameters at any level of follow-up. Improvement in OSS between groups was significant only at 3 months but not subsequently. CONCLUSION: Septoplasty with/without BIT is helpful in treating patients with DNS and refractory AR. However, although adding BIT brings significant benefit in decreasing nasal obstruction, it does not significantly improve the Subjective Performance parameters during follow-up, except for OSS at the third month.

Solid-state fermentation-based enzyme-assisted extraction of eicosapentaenoic acid-rich oil from Nannochloropsis sp.

Enzymatic treatment of microalgal biomass is a promising approach for extraction of microalgal lipid, but high cost of commercially sourcing enzyme is a major drawback in industrial implementation. Present study involves extraction of eicosapentaenoic acid-rich oil from Nannochloropsis sp. biomass using low cost cellulolytic enzymes produced from Trichoderma reesei in a solid-state fermentation bioreactor. Maximum total fatty acid recovery of 369.4 ± 4.6 mg/g dry weight (total fatty acid yield of 77%) was achieved in 12 h from the enzymatically treated microalgal cells, of which the eicosapentaenoic acid content was 11%. Sugar release of 1.70 ± 0.05 g/L was obtained post enzymatic treatment at 50 °C. The enzyme was reused thrice for cell wall disruption without compromising on total fatty acid yield. Additionally, high protein content of 47% in the defatted biomass could be explored as a potential aquafeed, thus enhancing the overall economics and sustainability of the process.

Altered glutathione homeostasis in heart augments cardiac lipotoxicity associated with diet-induced obesity in mice.

Obesity-related cardiac lipid accumulation is associated with increased myocardial oxidative stress. The role of the antioxidant glutathione in cardiac lipotoxicity is unclear. Cystathionine ß-synthase (Cbs) catalyzes the first step in the trans-sulfuration of homocysteine to cysteine, which is estimated to provide ∼50% of cysteine for hepatic glutathione biosynthesis. As cardiac glutathione is a reflection of the liver glutathione pool, we hypothesize that mice heterozygous for targeted disruption of Cbs (Cbs(+/-)) are more susceptible to obesity-related cardiolipotoxicity because of impaired liver glutathione synthesis. Cbs(+/+) and Cbs(+/-) mice were fed a high fat diet (60% energy) from weaning for 13 weeks to induce obesity and had similar increases in body weight and body fat. This was accompanied by increased hepatic triglyceride but no differences in hepatic glutathione levels compared with mice fed chow. However, Cbs(+/-) mice with diet-induced obesity had greater glucose intolerance and lower total and reduced glutathione levels in the heart, accompanied by lower plasma cysteine levels compared with Cbs(+/+) mice. Higher triglyceride concentrations, increased oxidative stress, and increased markers of apoptosis were also observed in heart from Cbs(+/-) mice with diet-induced obesity compared with Cbs(+/+) mice. This study suggests a novel role for Cbs in maintaining the cardiac glutathione pool and protecting against cardiac lipid accumulation and oxidative stress during diet-induced obesity in mice.

Jute sticks biomass delignification through laccase-mediator system for enhanced saccharification and sustainable release of fermentable sugar.

Jute sticks obtained after the extraction of jute fiber are an excellent biomass feedstock with a significant amount of carbohydrates that makes it an attractive resource for sustainable energy generation. However, the high lignin content in the jute stick hinders the cellulosic component of the cell wall from enzymatic hydrolysis.This work demonstrates the lignin degradation of jute stick biomass by Trametes maxima laccase in the presence of mediator Hydroxybenzotriazole and improvement in its subsequent saccharification. Lignin component in jute stick is reduced by 21.8% in a single reaction treatment with laccase-mediator compared to the untreated jute stick sample used as control. The yield of fermentable sugar is increased by 19.5% that verifies enhanced saccharification after lignin removal. Delignification of jute stick was corroborated through different analytical techniques. The Pyrolysis gas chromatography/mass spectrometry results further confirms abundance of S lignin unit in the jute stick compared to the H and G unit and modification in lignin polymer as a change in the syringyl-to-guaiacyl ratio. Hence, this work demonstrates that jute stick can be effectively delignified using biocatalyst-mediator system and utilized as biomass source, thus contributing in circular bio-economy through waste valorization.

Dietary adherence to the Mediterranean diet pattern in a randomized clinical trial of patients with quiescent ulcerative colitis.

Background: The Mediterranean diet pattern (MDP) is believed to improve health and promote balanced inflammation and metabolism. While unknown, compelling evidence suggests that MDP could benefit patients with inflammatory bowel disease (IBD). We aimed to evaluate the level of diet adherence, diet quality, and nutritional adequacy of the MDP in patients with Ulcerative Colitis (UC). Methods: Adult participants (n = 32) with quiescent UC were randomized to follow a MDP (n = 18) or Canadian Habitual Diet (CHD) (n = 14) for 12 weeks. The MDP participants received tailored nutrition education from a Registered Dietitian. Demographic, clinical data, medical history, and quality of life were assessed with the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), dietary adherence with the Mediterranean Diet Serving Score (MDSS), diet quality via the Healthy Eating Index-2015 (HEI-2015), and dietary intake (ASA-24) were completed at baseline and week 12. Results: Participants' diets were analyzed (MDP n = 15, CHD n = 13). The MDP (n = 10, 67%) achieved a high level of adherence (MDSS score between 16 and 24) vs. CHD (n = 3), (p = 0.030). HEI-2015 significantly increased from baseline to week 12 (p = 0.007) in the MDP and was significantly higher at week 12 compared to the CHD (p = 0.0001). The SIBDQ (bowel domain) showed reductions in the passage of large amounts of gas (p = 0.01) and improvements in tenesmus (p = 0.03) in the MDP. Despite enhanced diet quality and adherence in the MDP, females had inadequate intakes of calcium, iron, vitamin D, vitamin E, and choline and males had inadequate intakes of fiber, vitamin D, vitamin E, and choline. No adverse events were reported. Conclusion: With nutrition education, high adherence to the MDP was achieved without an increase in bowel symptoms. Following the MDP led to a higher diet quality; however, nutritional inadequacies were identified. Tailored dietary education focusing on nutrients of concern when following the MDP is recommended to ensure nutritional adequacy. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT03053713].

A Mediterranean-like fat blend protects against the development of severe colitis in the mucin-2 deficient murine model.

There is a growing appreciation that the interaction between diet, the gut microbiota and the immune system contribute to the development and progression of inflammatory bowel disease (IBD). A mounting body of scientific evidence suggests that high-fat diets exacerbate IBD; however, there is a lack of information on how specific types of fat impact colitis. The Mediterranean diet (MD) is considered a health-promoting diet containing approximately 40% total fat. It is not known if the blend of fats found in the MD contributes to its beneficial protective effects.Mice deficient in the mucin 2 gene (Muc 2-/-) were weaned to 40% fat, isocaloric, isonitrogenous diets. We compared the MD fat blend (high monounsaturated, 2:1 n-6:n-3 polyunsaturated and moderate saturated fat) to diets composed of corn oil (CO, n-6 polyunsaturated-rich), olive oil (monounsaturated-rich) or milk fat (MF, saturated-rich) on spontaneous colitis development in Muc2-/- mice. The MD resulted in lower clinical and histopathological scores and induced tolerogenic CD103+ CD11b+ dendritic, Th22 and IL-17+ IL-22+ cells necessary for intestinal barrier repair. The MD was associated with beneficial microbes and associated with higher cecal acetic acid levels negatively correlated with colitogenic microbes like Akkermansia muciniphila. In contrast, CO showed a higher prevalence of mucin-degraders including A. muciniphila and Enterobacteriaceae, which have been associated with colitis.A dietary blend of fats mimicking the MD, reduces disease activity, inflammation-related biomarkers and improves metabolic parameters in the Muc2-/- mouse model. Our findings suggest that the MD fat blend could be incorporated into a maintenance diet for colitis.

Interleukin-11 reduces TLR4-induced colitis in TLR2-deficient mice and restores intestinal STAT3 signaling.

BACKGROUND & AIMS: The roles of intestinal Toll-like receptors (TLR) in the pathogenesis of colitis are not known. TLR2 and TLR4 appear to protect against dextran sodium sulfate-induced colitis by promoting mucosal integrity, but it is not clear whether this method of protection occurs in other models of colitis. We investigated the roles of TLR2 and TLR4 and the cell types that express these receptors during infectious colitis. METHODS: We generated chimeric mice with TLR2(-/-) or TLR4(-/-) bone marrow and infected them with the bacterial pathogen Citrobacter rodentium. We assessed their susceptibility to colitis and the mechanisms of TLR-mediated mucosal integrity. RESULTS: TLR2-expressing tissue resident cells prevented lethal colitis, whereas TLR4-dependent inflammatory responses of hematopoietic cells mediated intestinal damage. TLR2 expression protected against intestinal damage by maintaining epithelial barrier function and inducing expression of interleukin (IL)-11 from tissue resident cells in the muscularis mucosae, concurrent with epithelial activation of the transcription factor STAT3. Addition of exogenous IL-11 protected against the lethal colitis in TLR2-deficient mice via STAT3 activation in intestinal epithelial cells. CONCLUSIONS: TLR2-dependent cytoprotective responses from tissue resident cells maintain mucosal integrity against the ultimately lethal TLR4-dependent inflammatory responses of hematopoietic cells. Whereas TLR2 protects against various noxious agents, the role of TLR4 during colitis can be either protective or damaging, depending on the stimulus. Therefore, therapeutics that reduce innate immunity (TLR2 signaling in particular) may not be beneficial to patients with colitis; they could worsen symptoms. Therapies that stimulate cytoprotective responses, like IL-11, could have benefits for patients with colitis.

The predictive power of serum vitamin D for poor outcomes in COVID-19 patients.

Considering the high prevalence of vitamin D deficiency worldwide and its relationship with immune response to viral infections, this study attempted to identify the predictive power of serum vitamin D for poor outcomes among the COVID-19 patients. This retrospective cohort study included all patients with confirmed COVID-19 hospitalized between February 20, 2020, and April 20, 2020, at a designated COVID-19 hospital, located in Tehran province, Iran. General characteristics, medical history and clinical symptoms were recorded by trained physicians. Blood parameters including complete blood count, creatinine, lactate dehydrogenase, creatine phosphokinase, erythrocyte sedimentation rate, C-reactive protein and vitamin D were tested. This study included 290 hospitalized patients with COVID-19 (the mean age [SD]: 61.6 [16.9], 56.6% males), of whom 142 had vitamin D concentrations less than 20 ng/ml, defined as vitamin D deficiency. COVID-19 patients with vitamin D deficiency were more likely to die (Crude OR [95% CI]: 2.30 [1.25-4.26]), require ICU (2.06 [1.22-3.46]) and invasive mechanical ventilation (2.03 [1.04-3.93]) based on univariate logistic regression results. Although, after adjusting for potentials confounders such as gender and age, the association between vitamin D and need to invasive mechanical ventilation lost its significance, adjusted values for the risk of death and ICU requirement were still statistically significant. Vitamin D deficiency can be considered as a predictor of poor outcomes and mortality in COVID-19 patients. Therefore, checking serum 25 (OH) D on admission and taking vitamin D supplements according to the prophylactic or treatment protocols is recommended for all COVID-19 patients.

Maternal Intake of Dietary Fat Pre-Programs Offspring's Gut Ecosystem Altering Colonization Resistance and Immunity to Infectious Colitis in Mice.

SCOPE: The transgenerational impact of dietary fat remains unclear. Here, the role of maternal fat consumption as a modulator of gut microbial communities and infectious disease outcomes in their offspring is explored. METHODS AND RESULTS: C57BL/6 mice are fed isocaloric high-fat diets throughout breeding, gestation and lactation. Diets contained either milk fat (MF), olive oil (OO) or corn oil (CO), with or without fish oil. The pups born to maternally exposed mice are weaned on to chow and raised into adulthood. At 8 weeks, the offsprings are either euthanized for colonic 16S rRNA analysis or challenged with the enteric pathogen, Citrobacter rodentium. Maternal CO exposure resulted in unique clustering of bacterial communities in offspring compared with MF and OO. Diets rich in CO reduced survival in offspring challenged with C. rodentium. The addition of fish oil did not improve mortality caused by CO and worsened disease outcomes when combined with OO. Unlike the unsaturated diets, MF is protective with and without fish oil. CONCLUSIONS: Overall, these data reveal that maternal intake of fatty acids do have transgenerational impacts on their offspring's bacteriome and enteric infection risk. Based on this study, saturated fats should be included in maternal diets.