Good girl goes bad: Understanding how gut commensals cause disease.

This review examines the complex connection between commensal microbiota and the development of opportunistic infections. Several underlying conditions, such as metabolic diseases and weakened immune systems, increase the vulnerability of patients to opportunistic infections. The increasing antibiotic resistance adds significant complexity to the management of infectious diseases. Although commensals have long been considered beneficial, recent research contradicts this notion by uncovering chronic illnesses linked to atypical pathogens or commensal bacteria. This review examines conditions in which commensal bacteria, which are usually beneficial, contribute to developing diseases. Commensals' support for opportunistic infections can be categorized based on factors such as colonization fitness, pathoadaptive mutation, and evasion of host immune response. Individuals with weakened immune systems are especially susceptible, highlighting the importance of mucosal host-microbiota interaction in promoting infection when conditions are inappropriate. Dysregulation of gut microbial homeostasis, immunological modulation, and microbial interactions are caused by several factors that contribute to the development of chronic illnesses. Knowledge about these mechanisms is essential for developing preventive measures, particularly for susceptible populations, and emphasizes the importance of maintaining a balanced gut microbiota in reducing the impact of opportunistic infections.

Prebiotics Plus Probiotics May Favorably Impact on Gut Permeability, Endocannabinoid Receptors, and Inflammatory Biomarkers in Patients with Coronary Artery Diseases: A Clinical Trial.

While gut-to-systemic translocation of pyrogenic endotoxin due to a leaky gut elicits systemic inflammation, at the intestine, the endocannabinoid system (eCB) also plays a major role in modulating the impact of gut dysbiosis on the host system. Therefore, we hypothesized that coadministration of prebiotic inulin with probiotics would improve the eCB system, gut microbial composition, and inflammatory parameters associated with coronary artery diseases (CAD). We designed a randomized, double-blind trial with 92 CAD patients. Patients were randomly allocated to receive inulin (15 mg/day), LGG capsules 1.9 × 109 colony-forming unit (CFU) or inulin plus probiotic (synbiotics) supplements, for a duration of 60 days. We assessed gut microbiota composition, expression of cannabinoid receptors (i.e., CB1 and CB2), serum levels of interleukin-6 (IL-6), toll-like receptor 4 (TLR-4), lipopolysaccharides (LPS), total antioxidant capacity (TAC), and malondialdehyde (MDA) before and after the supplementation. Probiotic-inulin cosupplementation significantly decreased IL6, LPS, and TLR-4 and increased serum TAC concentrations compared with the placebo. While CB1 receptor expression had no difference, significant differences were observed for the CB2 receptor expression among the four treatments. CB2 receptor mRNA expression significantly (p < .05) correlated with serum levels of LPS (r = -.10) and F/B ratio (r = -.407, p = .047). Our data collectively provide preliminary evidence that gut microbiota determines gut permeability through the LPS-eCB system. We also have found that synbiotics improved the eCB receptors, and inflammatory biomarkers more than either of the two supplementations given alone.

Oleander attenuates hepatic inflammation in a TLR4-independent manner and by favorable modulation of hepatocellular global metabolome that supports cytoprotection.

ETHNOPHARMACOLOGICAL RELEVANCE: Nerium oleander is used to treat liver-associated chronic metabolic diseases in traditional medicinal systems across the globe. The hepatoprotective effects of oleander are mentioned in Indian and Chinese traditional medicinal literature. AIM OF THE STUDY: The present study aimed to investigate the cellular mechanisms behind the hepatoprotective effects of a non-toxic dose of oleander (NO). MATERIALS AND METHODS: The hepatoprotective effects of NO were tested against lipopolysaccharide (LPS)-treated HepG2 cells. Oxidative stress response was studied using cellular enzymatic assays, and gene expression was analyzed using qRT-PCR. HepG2 cells were pretreated with TAK-242 (pharmacological inhibitor of TLR4) to decipher the anti-inflammatory mechanisms of NO. Cell-free metabolites were analyzed using GCMS and were subjected to pathway enrichment analysis. RESULTS: NO reduced systemic inflammation, serum lipid peroxidation byproducts, and glucose without affecting serum transaminase levels and hepatic histopathological features. NO attenuated the inflammation-induced loss of antioxidant enzyme activities and mRNA expressions of toll-like receptor-4 (TLR4)/nuclear factor κß (NFκß)-dependent inflammatory genes. In TAK-242 pretreated cells, LPS was unable to induce inflammatory and oxidative responses. However, NO treatment in TAK-242 pretreated cells with LPS stimulation further reduced the signs of inflammation and improved hepatoprotective activities. A comparative analysis of the intracellular global metabolome from HepG2 cells with and without NO treatment indicated NO-mediated favorable modulation of intracellular metabolic pathways that support cytoprotective activities. CONCLUSION: NO protects HepG2 cells from LPS-induced oxidative and inflammatory injury. The hepatoprotective effects of NO are mediated by a TLR4-independent process and through a favorable modulation of the intracellular global metabolome that supports cytoprotection.

The intestinal-level metabolic benefits of green tea catechins: Mechanistic insights from pre-clinical and clinical studies.

BACKGROUND: The intestinal-level host-microbiota interaction has been implicated in the pathogenesis of chronic diseases. The current review is intended to provide a comprehensive insight into deciphering whether intestinal-level bioactivities mediate the overall metabolic health benefits of green tea catechins. PURPOSE: We have comprehensively discussed pre-clinical and clinical evidences of intestinal-level changes in metabolism, microbiota, and metabolome due to catechin-rich green tea treatments, ultimately limiting metabolic diseases. Exclusive emphasis has been given to purified catechins and green tea, and discussions on extraintestinal mechanisms of metabolic health benefits were avoided. METHODS: A literature search for relevant pre-clinical and clinical studies was performed in various online databases (e.g., PubMed) using specific keywords (e.g., catechin, intestine, microbiota). Out of all the referred literature, ∼15% belonged to 2021-2023, ∼51% were from 2011-2020, and ∼32% from 2000-2010. RESULT: The metabolic health benefits of green tea catechins are indeed influenced by the intestinal-level bioactivities, including reduction of mucosal inflammation and oxidative stress, attenuation of gut barrier dysfunction, decrease in intestinal lipid absorption and metabolism, favorable modulation of mucosal nuclear receptor signaling, alterations of the luminal global metabolome, and mitigation of the gut dysbiosis. The results from the recent clinical studies support the pre-clinical evidences. The challenges and pitfalls of the currently available knowledge on catechin bioactivities have been discussed, and constructive directions to harness the translational benefits of green tea through future interventions have been provided. CONCLUSION: The metabolism, metabolome, and microbiota at the intestinal epithelia play critical roles in catechin metabolism, pharmacokinetics, bioavailability, and bioactivities. Especially the reciprocal interaction between the catechins and the gut microbiota dictates the metabolic benefits of catechins.

The oral microbial odyssey influencing chronic metabolic disease.

INTRODUCTION: Since the oral cavity is the gateway to the gut, oral microbes likely hold the potential to influence metabolic disease by affecting the gut microbiota. METHOD: A thorough review of literature has been performed to link the alterations in oral microbiota with chronic metabolic disease by influencing the gut microbiota. RESULT: A strong correlation exists between abnormalities in oral microbiota and several systemic disorders, such as cardiovascular disease, diabetes, and obesity, which likely initially manifest as oral diseases. Ensuring adequate oral hygiene practices and cultivating diverse oral microflora are crucial for the preservation of general well-being. Oral bacteria have the ability to establish and endure in the gastrointestinal tract, leading to the development of prolonged inflammation and activation of the immune system. Oral microbe-associated prophylactic strategies could be beneficial in mitigating metabolic diseases. CONCLUSION: Oral microbiota can have a profound impact on the gut microbiota and influence the pathogenesis of metabolic diseases.

Improved antioxidant activities of spice require enrichment of distinct yet closely-related metabolic pathways.

Improved biosynthesis of commercially and pharmacologically relevant phytometabolites through genetic and metabolic engineering is a lucrative strategy for crop improvement. However, identifying appropriate biosynthetic pathways pertaining to specific bioactivities has been challenging since the major metabolic pathways remain closely interconnected. Here we propose a reverse association strategy in which, based on the phytochemical profile, putative target metabolic pathways could be identified for increased production of phytochemicals. Dried seed fruits of Coriandrum sativum, Trachyspermum ammi, Cuminum cyminum, and Foeniculum vulgare (family Apiaceae) were subjected to untargeted gas chromatography-mass spectrometry-based phytochemical profiling followed by evaluation of the overall antioxidant profile using multiple antioxidant assays. Using bioinformatics approaches, specific phytochemical classes and the enrichment of their respective biosynthetic pathways were identified. Collectively, the data suggest enrichment of isoprenoids and fatty acids biosynthetic pathways. The close association of metabolic pathways with antioxidant capacities indicated a need for enrichment of specific yet closely-related metabolic pathways to achieve an improved quality of spices for better antioxidant effects.

Rise of the guardians: Gut microbial maneuvers in bacterial infections.

AIMS: Bacterial infections are one of the major causes of mortality globally. The gut microbiota, primarily comprised of the commensals, performs an important role in maintaining intestinal immunometabolic homeostasis. The current review aims to provide a comprehensive understanding of how modulation of the gut microbiota influences opportunistic bacterial infections. MATERIALS AND METHODS: Primarily centered around mechanisms related to colonization resistance, nutrient, and metabolite-associated factors, mucosal immune response, and commensal-pathogen reciprocal interactions, we discuss how gut microbiota can promote or prevent bacterial infections. KEY FINDINGS: Opportunistic infections can occur directly due to obligate pathogens or indirectly due to the overgrowth of opportunistic pathobionts. Gut microbiota-centered mechanisms of altered intestinal immunometabolic and metabolomic homeostasis play a significant role in infection promotion and prevention. Depletion in the population of commensals, increased abundance of pathobionts, and overall decrease in gut microbial diversity and richness caused due to prolonged antibiotic use are risk factors of opportunistic bacterial infections, including infections from multidrug-resistant spp. Gut commensals can limit opportunistic infections by mechanisms including the production of antimicrobials, short-chain fatty acids, bile acid metabolism, promoting mucin formation, and maintaining immunological balance at the mucosa. Gut microbiota-centered strategies, including the administration of probiotics and fecal microbiota transplantation, could help attenuate opportunistic bacterial infections. SIGNIFICANCE: The current review discussed the gut microbial population and function-specific aspects contributing to bacterial infection susceptibility and prophylaxis. Collectively, this review provides a comprehensive understanding of the mechanisms related to the dual role of gut microbiota in bacterial infections.

Chemically Defined Lactobacillus plantarum Cell-Free Metabolites Demonstrate Cytoprotection in HepG2 Cells through Nrf2-Dependent Mechanism.

Centering around the concept that metabolites from the gut commensals can exert metabolic health benefits along the gut-liver axis, we tested whether the cell-free global metabolome of probiotic bacteria can exert hepatoprotective benefits against H2O2-induced oxidative stress. Cell-free global metabolites of Lactobacillus plantarum (LPM) were isolated and untargeted metabolomics was performed. The free radical scavenging potentials of LPM were measured. The cytoprotective effects of LPM were tested on HepG2 cells. A total of 66 diverse metabolites were identified in LPM, among which saturated fatty acids, amino acids and dicarboxylic acids were highly enriched. LPM attenuated cell damage, lipid peroxidation and the levels of intracellular cytoprotective enzymes in H2O2-treated cells. LPM also attenuated H2O2-induced increased expressions of TNF-α and IL-6. However, the cytoprotective effects of LPM were diminished in cells that were pretreated with a pharmacological inhibitor of Nrf2. Our data collectively indicate that LPM can significantly attenuate oxidative damage to HepG2 cells. However, the cytoprotective effects of LPM likely depend on an Nrf2-dependent mechanism.

Bacterial exopolysaccharides as emerging bioactive macromolecules: from fundamentals to applications.

Microbial exopolysaccharides (EPS) are extracellular carbohydrate polymers forming capsules or slimy coating around the cells. EPS can be secreted by various bacterial genera that can help bacterial cells in attachment, environmental adaptation, stress tolerance and are an integral part of microbial biofilms. Several gut commensals (e.g., Lactobacillus, Bifidobacterium) produce EPS that possess diverse bioactivities. Bacterial EPS also has extensive commercial applications in the pharmaceutical and food industries. Owing to the structural and functional diversity, genetic and metabolic engineering strategies are currently employed to increase EPS production. Therefore, the current review provides a comprehensive overview of the fundamentals of bacterial exopolysaccharides, including their classification, source, biosynthetic pathways, and functions in the microbial community. The review also provides an overview of the diverse bioactivities of microbial EPS, including immunomodulatory, anti-diabetic, anti-obesity, and anti-cancer properties. Since several gut microbes are EPS producers and gut microbiota helps maintain a functional gut barrier, emphasis has been given to the intestinal-level bioactivities of the gut microbial EPS. Collectively, the review provides a comprehensive overview of microbial bioactive exopolysaccharides.

A toxic shrub turned therapeutic: The dichotomy of Nerium oleander bioactivities.

Nerium oleander L. is a medicinal plant, used for the treatment of cancers and hyperglycemia across the world, especially in Indian sub-continent, Turkey, Morocco, and China. Although clinical studies supporting its pharmacological effects remain critically underexplored, accidental and intentional consumption of any part of the plant causes fatal toxicity in animals and humans. While the polyphenolic fraction of oleander leaves has been attributed to its pre-clinical pharmacological activities, the presence of diverse cardiac glycosides (especially oleandrin) causes apoptosis to cancer cells in vitro and results in clinical signs of oleander poisoning. Thus, the dual pharmacological and toxicological role of oleander is a perplexing dichotomy in phytotherapy. The current investigative review, therefore, intended to analyze the intrinsic and extrinsic factors that likely contribute to this conundrum. Especially by focusing on gut microbial diversity, abundance, and metabolic functions, oleander-associated pharmacological and toxicological studies have been critically analyzed to define the dual effects of oleander. Electronic databases were extensively screened for relevant research articles (including pre-clinical and clinical) related to oleander bioactivities and toxicity. Taxonomic preference was given to the plant N. oleander L. and synonymous plants as per 'The World Flora Online' database (WCSP record #135196). Discussion on yellow oleander (Cascabela thevetia (L.) Lippold) has intentionally been avoided since it is a different plant. The review indicates that the gut microbiota likely plays a key role in differentially modulating the pharmacological and toxicological effects of oleander. Other factors identified influencing the oleander bioactivities include dose and mode of treatment, cardiac glycoside pharmacokinetics, host-endogenous glycosides, plant material processing and phytochemical extraction methods, plant genotypic variations, environmental effects on the phytochemical quality and quantity, gene expression variations, host dietary patterns and co-morbidity, etc. The arguments proposed are also relevant to other medicinal plants containing toxic cardiac glycosides.

The opportunistic nature of gut commensal microbiota.

The abundance of gut commensals has historically been associated with health-promoting effects despite the fact that the definition of good or bad microbiota remains condition-specific. The beneficial or pathogenic nature of microbiota is generally dictated by the dimensions of host-microbiota and microbe-microbe interactions. With the increasing popularity of gut microbiota in human health and disease, emerging evidence suggests opportunistic infections promoted by those gut bacteria that are generally considered beneficial. Therefore, the current review deals with the opportunistic nature of the gut commensals and aims to summarise the concepts behind the occasional commensal-to-pathogenic transformation of the gut microbes. Specifically, relevant clinical and experimental studies have been discussed on the overgrowth and bacteraemia caused by commensals. Three key processes and their underlying mechanisms have been summarised to be responsible for the opportunistic nature of commensals, viz. improved colonisation fitness that is dictated by commensal-pathogen interactions and availability of preferred nutrients; pathoadaptive mutations that can trigger the commensal-to-pathogen transformation; and evasion of host immune response as a survival and proliferation strategy of the microbes. Collectively, this review provides an updated concept summary on the underlying mechanisms of disease causative events driven by gut commensal bacteria.

Association of dietary inflammatory index with chronic kidney disease and kidney stones in Iranian adults: A cross-sectional study within the Ravansar non-communicable diseases cohort.

Chronic inflammation plays a central role in the pathogenesis of chronic kidney disease (CKD). The association of dietary inflammatory index (DII) with CKD remains underexplored. Thus, the present study aimed to determine the association between the DII, risk of CKD, and kidney stone formation using the data from the Ravansar non-communicable diseases (RaNCD) cohort study conducted in Kermanshah, Iran. The cross-sectional study was conducted using the recruitment phase data of the RaNCD cohort study comprising 9,824 individuals with an age range of 35-65 years. Food frequency questionnaires (FFQ) were used to evaluate the association between diet and DII scores. Renal function was assessed using estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and serum creatinine (Cr) level. CKD was defined based on eGFR. The prevalence of kidney stones was evaluated by participants' self-report. A total of 1,791 participants (18.24%) had kidney stones, while a majority were in the first quartile (27.69%). Out of 9,824 subjects, 1,747 subjects (eGFR: 18.50 ml/min per 1.73 m2; 95% CI: 17.72-19.30) had CKD. A significant trend for eGFR across all quartiles (Qs) of DII was observed. The odds ratio of CKD in the fourth quartile (pro-inflammatory diet) was 4.38-times higher than in the first quartile (anti-inflammatory diet) of DII (95% CI = 3.58-5.36). Women were found to be more likely to have less eGFR than men in the DII Qs. Collectively, the findings indicated that consumption of a pro-inflammatory diet was associated with a high occurrence of CKD. As a matter of interest, the results also revealed that a pro-inflammatory diet had no significant correlation with kidney stone development.

EGCG and catechin relative to green tea extract differentially modulate the gut microbial metabolome and liver metabolome to prevent obesity in mice fed a high-fat diet.

Green tea extract (GTE) alleviates obesity, in part, by modulating gut microbial composition and metabolism. However, direct evidence regarding the catechin-specific bioactivities that are responsible for these benefits remain unclear. The present study therefore investigated dietary supplementation of GTE, epigallocatechin gallate (EGCG), or (+)-catechin (CAT) in male C57BL6/J mice that were fed a high-fat (HF) diet to establish the independent contributions of EGCG and CAT relative to GTE to restore microbial and host metabolism. We hypothesized that EGCG would regulate the gut microbial metabolome and host liver metabolome more similar to GTE than CAT to explain their previously observed differential effects on cardiometabolic health. To test this, we assessed metabolic and phenolic shifts in liver and fecal samples during dietary HF-induced obesity. Ten fecal metabolites and ten liver metabolites (VIP > 2) primarily contributed to the differences in the metabolome among different interventions. In fecal samples, nine metabolic pathways (e.g., tricarboxcylic acid cycle and tyrosine metabolism) were differentially altered between the GTE and CAT interventions, whereas three pathways differed between GTE and EGCG interventions, suggesting differential benefits of GTE and its distinctive bioactive components on gut microbial metabolism. Likewise, hepatic glycolysis / gluconeogenesis metabolic pathways were significantly altered between GTE and EGCG interventions, while only hepatic tyrosine metabolism was altered between CAT and GTE interventions. Thus, our findings support that purified catechins relative to GTE uniquely contribute to regulating host and microbial metabolic pathways such as central energy metabolism to protect against metabolic dysfunction leading to obesity.

Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches.

Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.

Daily Inclusion of Resistant Starch-Containing Potatoes in a Dietary Guidelines for Americans Dietary Pattern Does Not Adversely Affect Cardiometabolic Risk or Intestinal Permeability in Adults with Metabolic Syndrome: A Randomized Controlled Trial.

Poor diet quality influences cardiometabolic risk. Although potatoes are suggested to adversely affect cardiometabolic health, controlled trials that can establish causality are limited. Consistent with potatoes being rich in micronutrients and resistant starch, we hypothesized that their inclusion in a Dietary Guidelines for Americans (DGA)-based dietary pattern would improve cardiometabolic and gut health in metabolic syndrome (MetS) persons. In a randomized cross-over trial, MetS persons (n = 27; 32.5 ± 1.3 year) consumed a DGA-based diet for 2 weeks containing potatoes (DGA + POTATO; 17.5 g/day resistant starch) or bagels (DGA + BAGEL; 0 g/day resistant starch) prior to completing oral glucose and gut permeability tests. Blood pressure, fasting glucose and insulin, and insulin resistance decreased (p < 0.05) from baseline regardless of treatment without any change in body mass. Oral glucose-induced changes in brachial artery flow-mediated dilation, nitric oxide homeostasis, and lipid peroxidation did not differ between treatment arms. Serum endotoxin AUC0−120 min and urinary lactulose/mannitol, but not urinary sucralose/erythritol, were lower in DGA + POTATO. Fecal microbiome showed limited between-treatment differences, but the proportion of acetate was higher in DGA + POTATO. Thus, short-term consumption of a DGA-based diet decreases cardiometabolic risk, and the incorporation of resistant starch-containing potatoes into a healthy diet reduces small intestinal permeability and postprandial endotoxemia.

Antiinflammatory phytochemicals against virus-induced hyperinflammatory responses: Scope, rationale, application, and limitations.

Uncontrolled inflammatory responses or cytokine storm associated with viral infections results in deleterious consequences such as vascular leakage, severe hemorrhage, shock, immune paralysis, multi-organ failure, and even death. With the emerging new viral infections and lack of effective prophylactic vaccines, evidence-based complementary strategies that limit viral infection-mediated hyperinflammatory responses could be a promising approach to limit host tissue injury. The present review emphasizes the potentials of antiinflammatory phytochemicals in limiting hyperinflammatory injury caused by viral infections. The predominant phytochemicals along with their mechanism in limiting hyperimmune and pro-inflammatory responses under viral infection have been reviewed comprehensively. How certain phytochemicals can be effective in limiting hyper-inflammatory response indirectly by favorably modulating gut microbiota and maintaining a functional intestinal barrier has also been presented. Finally, we have discussed improved systemic bioavailability of phytochemicals, efficient delivery strategies, and safety measures for effective antiinflammatory phytotherapies, in addition to emphasizing the requirement of tightly controlled clinical studies to establish the antiinflammatory efficacy of the phytochemicals. Collectively, the review provides a scooping overview on the potentials of bioactive phytochemicals to mitigate pro-inflammatory injury associated with viral infections.

The intestinal 3M (microbiota, metabolism, metabolome) zeitgeist - from fundamentals to future challenges.

The role of the intestine in human health and disease has historically been neglected and was mostly attributed to digestive and absorptive functions. In the past two decades, however, discoveries related to human nutrition and intestinal host-microbe reciprocal interaction have established the essential role of intestinal health in the pathogenesis of chronic diseases and the overall wellbeing. That transfer of gut microbiota could be a means of disease phenotype transfer has revolutionized our understanding of chronic disease pathogenesis. This narrative review highlights the major concepts related to intestinal microbiota, metabolism, and metabolome (3M) that have facilitated our fundamental understanding of the association between the intestine, and human health and disease. In line with increased interest of microbiota-dependent modulation of human health by dietary phytochemicals, we have also discussed the emerging concepts beyond the phytochemical bioactivities which emphasizes the integral role of microbial metabolites of parent phytochemicals at extraintestinal tissues. Finally, this review concludes with challenges and future prospects in defining the 3M interactions and has emphasized the fact that, it takes 'guts' to stay healthy.

Dietary Inflammatory Index in relation to psoriasis risk, cardiovascular risk factors, and clinical outcomes: a case-control study in psoriasis patients.

Psoriasis is an inflammatory skin disease. Despite the understanding of disease pathogenesis, the link between diet-induced inflammation and the risk of psoriasis remains underexplored. Therefore, we examined the capability of the literature-derived energy-adjusted Dietary Inflammatory Index (E-DII) as a predictive tool for inflammation, incidence, and severity of psoriasis (as indexed by the Psoriasis Area Severity Index (PASI)). We conducted a case-control study of 149 adults (75 cases and 74 controls). The E-DII score was calculated based on the dietary intake that was evaluated using a validated 168 item quantity food-frequency questionnaire. The E-DII tertile cut-offs were categorized based on the following cut points: tertiles 1 ≤ -1.99; tertiles 2 = -2.00 to 0.60; tertile 3 ≥ 0.61. Logistic regression models were used to estimate the multivariable odds ratio (OR) adjusted for confounders. Patients with higher pro-inflammatory E-DII had a 3.60-times increased risk of psoriasis relative to patients in tertiles 1 (E-DIIT3 vs E-DIIT1: OR = 3.64; 95% confidence interval (CI) 1.51 to 8.79, P = 0.005). The severity of disease as indexed by PASI remained associated with E-DII (E-DIIT3 vs E-DIIT1: OR = 3.64; 95% CI 1.74 to 7.57, P = 0.015). For each unit increase in E-DII, the probability of disease severity is increased 3 times. Patients consuming a more pro-inflammatory diet were at a greater risk of psoriasis. These patients also demonstrated increased disease severity relative to individuals consuming a more anti-inflammatory diet. Novelty: A pro-inflammatory diet is associated with higher psoriasis incidence. Subjects with higher DII scores had higher inflammatory markers levels.

Pharmacological benefits of Acacia against metabolic diseases: intestinal-level bioactivities and favorable modulation of gut microbiota.

CONTEXT: Obesity-associated chronic metabolic disease is a leading contributor to mortality globally. Plants belonging to the genera Acacia are routinely used for the treatment of diverse metabolic diseases under different ethnomedicinal practices around the globe. OBJECTIVE: The current review centres around the pharmacological evidence of intestinal-level mechanisms for metabolic health benefits by Acacia spp. RESULTS: Acacia spp. increase the proportions of gut commensals (Bifidobacterium and Lactobacillus) and reduces the population of opportunistic pathobionts (Escherichia coli and Clostridium). Acacia gum that is rich in fibre, can also be a source of prebiotics to improve gut health. The intestinal-level anti-inflammatory activities of Acacia are likely to contribute to improvements in gut barrier function that would prevent gut-to-systemic endotoxin translocation and limit "low-grade" inflammation associated with metabolic diseases. CONCLUSION: This comprehensive review for the first time has emphasised the intestinal-level benefits of Acacia spp. which could be instrumental in limiting the burden of metabolic disease.