Harnessing Oxylipins and Inflammation Modulation for Prevention and Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 (n - 6) PUFAs and low levels of omega-3 (n - 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of n - 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics.

Omega-3 Fatty Acids for the Management of Osteoarthritis: A Narrative Review.

Osteoarthritis (OA) is a disease which results in degeneration of cartilage within joints and affects approximately 13.6% of adults over 20 years of age in Canada and the United States of America. OA is characterized by a state of low-grade inflammation which leads to a greater state of cellular catabolism disrupting the homeostasis of cartilage synthesis and degradation. Omega-3 polyunsaturated fatty acids (PUFAs) have been postulated as a potential therapeutic treatment option for individuals with OA. Omega-3 PUFAs are recognized for their anti-inflammatory properties, which could be beneficial in the context of OA to moderate pro-inflammatory markers and cartilage loss. The purpose of this narrative review is to outline recent pre-clinical and clinical evidence for the use of omega-3 in the management of OA.

Supplementation with omega-3 or omega-6 fatty acids attenuates platelet reactivity in postmenopausal women.

Postmenopausal women are at increased risk for a cardiovascular event due to platelet hyperactivity. There is evidence suggesting that ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have cardioprotective effects in these women. However, a mechanistic understanding of how these fatty acids regulate platelet function is unknown. In this study, we supplemented postmenopausal women with fish oil (ω-3 fatty acids) or evening primrose oil (ω-6 fatty acids) and investigated the effects on their platelet activity. The effects of fatty acid supplementation on platelet aggregation, dense granule secretion, and activation of integrin αIIbß3 at basal levels and in response to agonist were tested in postmenopausal women following a supplementation and washout period. Supplementation with fish oil or primrose oil attenuated the thrombin receptor PAR4-induced platelet aggregation. Supplementation with ω-3 or ω-6 fatty acids decreased platelet dense granule secretion and attenuated basal levels of integrin αIIbß3 activation. Interestingly, after the washout period following supplementation with primrose oil, platelet aggregation was similarly attenuated. Additionally, for either treatment, the observed protective effects post-supplementation on platelet dense granule secretion and basal levels of integrin activation were sustained after the washout period, suggesting a long-term shift in platelet reactivity due to fatty acid supplementation. These findings begin to elucidate the underlying mechanistic effects of ω-3 and ω-6 fatty acids on platelet reactivity in postmenopausal women. Hence, this study supports the beneficial effects of fish oil or primrose oil supplementation as a therapeutic intervention to reduce the risk of thrombotic events in postmenopausal women. https://clinicaltrials.gov/ct2/show/NCT02629497.

Randomized Controlled Trial of Omega-3 and -6 Fatty Acid Supplementation to Reduce Inflammatory Markers in Children with Autism Spectrum Disorder.

This double-blind, randomized controlled trial, tested fatty acid (FA) supplementation in children (ages 2- < 6 years) recently diagnosed with Autism Spectrum Disorder (ASD). Participants received daily oral FA supplement containing omega-3 and omega-6 FA, or a placebo for 90 days based on participant weight. Erythrocyte FAs and the cytokines, IL-1ß, IL-2, IFNγ, were measured in plasma obtained from serial blood collections. Treatment increased omega-3 and omega-6 FA levels (1.40 mol% for EPA and 1.62 mol% for DHA) and reduced IL-2 levels compared to placebo (- 0.17 pg/mL, 95% CI - 0.31, - 0.02, d = - 0.62). Omega 3-6 treatment was tolerable and adherence was greater than 70%. Future research will assess the effects of Omega 3-6 treatment on ASD symptoms. Registered on 06/08/2018 with ClinicalTrials.gov: NCT03550209.

Effect of a Novel Omega-3 and Omega-6 Fatty Acid Supplement on Dry Eye Disease: A 3-month Randomized Controlled Trial.

SIGNIFICANCE: Supplementing diet with a novel combination of omega-3 and omega-6 fatty acids significantly improved symptoms in extremely symptomatic participants with dry eye disease (DED). PURPOSE: This study aimed to determine the effect of daily intake of a novel combination of essential fatty acids on signs and symptoms of DED. METHODS: Participants with moderate to severe DED were enrolled in a prospective, randomized, double-masked parallel group study. Participants ingested either the treatment supplement containing omega-3 and omega-6 fatty acids (1200 mg eicosapentaenoic acid, 300 mg docosahexaenoic acid, 150 mg γ-linoleic acid) or the placebo (coconut and olive oil) daily for 3 months. To determine compliance, Omega-3 Index blood tests were conducted. At baseline and at 1 and 3 months, the following assessments were conducted: Ocular Surface Disease Index (OSDI) questionnaire and Symptom Assessment Questionnaire in Dry Eye, noninvasive tear breakup time, tear meniscus height, tear osmolarity, ocular redness, surface staining, Schirmer test, and meibography. RESULTS: Fifty participants (mean ± standard deviation baseline OSDI score, 52.2 ± 16.5) completed the study: 24 randomized to treatment and 26 randomized to placebo. Although there was an improvement in OSDI score at 3 months for both groups (treatment: -13.4 points, P = .003; placebo: -7.8 points, P = .02), participants with baseline OSDI scores >52 demonstrated an even larger significant improvement in symptoms with the treatment at 3 months compared with baseline (n = 13, -20.8 points, P = .002). There were no significant changes in any of the ocular assessments at 1 or 3 months (all P > .05). After 3 months, Omega-3 Index increased by 34% in the treatment group (baseline, 5.3 ± 0.8; 3 months, 8.0 ± 2.1; P < .001) and did not change in the placebo group (baseline, 4.8 ± 0.8; 3 months, 4.8 ± 0.6; P = .95). CONCLUSIONS: Supplementation with eicosapentaenoic acid, docosahexaenoic acid, and γ-linoleic acid resulted in a significant and clinically meaningful improvement of dry eye symptoms in extremely symptomatic participants with DED (OSDI ≥52).

Neuroaspis PLP10™, a nutritional formula rich in omega-3 and omega-6 fatty acids with antioxidant vitamins including gamma-tocopherol in early Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

In the present study, we investigated whether Neuroaspis PLP10™, a well-designed intervention, rich in omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) with specific antioxidant vitamins, may exert positive action in the improvement of Parkinson's disease symptoms and perhaps delay the progression of the disease when used as an adjuvant to the conventional treatment. Forty patients were randomized 1:1 to receive either 20 ml dose, once daily, of control (pure virgin olive oil) or Neuroaspis PLP 10™, a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure gamma (γ)-tocopherol (760 mg), for a total of 30 months in a randomized double-blind, placebo-controlled trial. Participants completed assessments based on the Hoehn and Yahr Staging Scale of Parkinson's Disease (HY scale) and the Unified Parkinson's Disease Rating Scale (UPDRS) III. Overall, for this small sample size clinical trial, Neuroaspis PLP10™ supplementation as an adjuvant treatment for 30 months in PD patients significantly delayed disease progression according to UPDRS (p ≤ 0.05) Vs placebo.

Microalgal Lipid Extracts Have Potential to Modulate the Inflammatory Response: A Critical Review.

Noncommunicable diseases (NCD) and age-associated diseases (AAD) are some of the gravest health concerns worldwide, accounting for up to 70% of total deaths globally. NCD and AAD, such as diabetes, obesity, cardiovascular disease, and cancer, are associated with low-grade chronic inflammation and poor dietary habits. Modulation of the inflammatory status through dietary components is a very appellative approach to fight these diseases and is supported by increasing evidence of natural and dietary components with strong anti-inflammatory activities. The consumption of bioactive lipids has a positive impact on preventing chronic inflammation and consequently NCD and AAD. Thus, new sources of bioactive lipids have been sought out. Microalgae are rich sources of bioactive lipids such as omega-6 and -3 polyunsaturated fatty acids (PUFA) and polar lipids with associated anti-inflammatory activity. PUFAs are enzymatically and non-enzymatically catalyzed to oxylipins and have a significant role in anti and pro-resolving inflammatory responses. Therefore, a large and rapidly growing body of research has been conducted in vivo and in vitro, investigating the potential anti-inflammatory activities of microalgae lipids. This review sought to summarize and critically analyze recent evidence of the anti-inflammatory potential of microalgae lipids and their possible use to prevent or mitigate chronic inflammation.

Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021.

Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose-response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.

Effects of Dietary n-3 and n-6 Polyunsaturated Fatty Acids in Inflammation and Cancerogenesis.

The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n-3 (omega-3) and n-6 (omega-6) to decrease the risk of metabolic disturbances. Consequently, excessive n-6 PUFAs content and high n-6/n-3 ratio are found in Western-type diet. The importance of a dietary n-6/n-3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n-3) and longer-chain n-3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n-3 PUFAs and oxylipins formed from n-6 PUFAs on inflammation. Evidence of PUFAs' role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.

Omega-3 Fatty Acids and Their Role in Pediatric Cancer.

BACKGROUND: Malnutrition is common in children with cancer and is associated with adverse clinical outcomes. The need for supportive care is becoming ever more evident and the role of nutrition in oncology is still not sufficiently understood. In particular, the consequences of macro- and micronutrient deficiencies require further research. As epidemiological data suggest anti-tumoral properties of omega-3 (n-3) polyunsaturated fatty acids (PUFAs), we reviewed the role of nutrition and n-3 supplementation in pediatric oncology. METHODS: A comprehensive literature search was conducted on PubMed through 5 February 2021 to select meta-analyses, systematic reviews, observational studies, and individual randomized controlled trials (RCTs) on macro- and micronutrient supplementation in pediatric oncology. The search strategy included the following medical subject headings (MeSH) and keywords: "childhood cancer", "pediatric oncology", "nutritional status", "malnutrition", and "omega-3-fatty-acids". The reference lists of all relevant articles were screened to include potentially pertinent studies. RESULTS: We summarize evidence about the importance of adequate nutrition in childhood cancer and the role of n-3 PUFAs and critically interpret findings. Possible effects of supplementation on the nutritional status and benefits during chemotherapy are discussed as well as strategies for primary and secondary prevention. CONCLUSION: We here describe the obvious benefits of omega-3 supplementation in childhood cancer. Further large scale clinical trials are required to verify potential anti-cancer effects of n-3 fatty acids.

Omega-3 Polyunsaturated Fatty Acids: Versatile Roles in Blood Pressure Regulation.

Significance: Hypertension is characterized as the imbalance of vasoconstriction and vasodilatation. Hypertension is influenced by genetic variation and environmental risk factors, such as unhealthy diet. Clinical trial results suggest that increasing intake of foods rich in n-3 polyunsaturated fatty acids (PUFAs) is beneficial for hypertension. Recent Advances: We summarized recent clinical trials regarding supplementation with n-3 PUFAs to reduce blood pressure (BP) in untreated hypertensive and normotensive subjects and systematically discussed the antihypertension mechanisms of n-3 PUFAs/n-3 oxylipins, including reducing oxidative stress, altering functions of membrane-related proteins, and competing with n-6 PUFAs/n-6 oxylipins in regulating vasodilator release. Critical Issues: Previous studies considered n-3 PUFAs as single molecules with beneficial roles in hypertension. Recently, researchers have paid more attention to the metabolism of n-3 PUFAs and explored molecular mechanisms of n-3 PUFAs and oxylipins derived from n-3 PUFAs in hypertension interventions. Future Directions: Based on the metabolism of n-3 PUFAs/n-3 oxylipins and mechanisms in BP control, we suggested that supplementation of n-3 PUFAs combined with agents targeting PUFA metabolism or the related signal pathways may amplify their effects to treat hypertension and other cardiovascular diseases. Antioxid. Redox Signal. 34, 800-810.

Exploring the role of LC-PUFA metabolism in pregnancy complications.

Maternal nutrition during pregnancy plays a significant role in growth and development of the placenta and influencing pregnancy outcome. Suboptimal nutritional status during early gestational period compromises the normal course of pregnancy leading to adverse maternal and fetal outcomes. Omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFA) are important for the growth and development of the placenta. Maternal fatty acids and their metabolites influence the normal course of pregnancy by regulating cell growth and development, cell signaling, regulate angiogenesis, modulate inflammatory responses and influence various structural and functional processes. Alterations in LC-PUFA and their metabolites may result in inadequate spiral artery remodeling or placental angiogenesis leading to structural and functional deficiency of the placenta which contributes to several pregnancy complications like preeclampsia, gestational diabetes mellitus, intrauterine growth restriction, and results in adverse birth outcomes. In this review, we summarize studies examining the role of fatty acids and their metabolites in pregnancy. We also discuss the possible molecular mechanisms through which LC-PUFA influences placental growth and development. Studies have demonstrated that omega-3 fatty acid supplementation lowers the incidence of preterm births, but its effect on reducing pregnancy complications are inconclusive.

Molecular changes in glaucomatous trabecular meshwork. Correlations with retinal ganglion cell death and novel strategies for neuroprotection.

Glaucoma is a chronic neurodegenerative disease characterized by retinal ganglion cell loss. Although significant advances in ophthalmologic knowledge and practice have been made, some glaucoma mechanisms are not yet understood, therefore, up to now there is no effective treatment able to ensure healing. Indeed, either pharmacological or surgical approaches to this disease aim in lowering intraocular pressure, which is considered the only modifiable risk factor. However, it is well known that several factors and metabolites are equally (if not more) involved in glaucoma. Oxidative stress, for instance, plays a pivotal role in both glaucoma onset and progression because it is responsible for the trabecular meshwork cell damage and, consequently, for intraocular pressure increase as well as for glaucomatous damage cascade. This review at first shows accurately the molecular-derived dysfunctions in antioxidant system and in mitochondria homeostasis which due to both oxidative stress and aging, lead to a chronic inflammation state, the trabecular meshwork damage as well as the glaucoma neurodegeneration. Therefore, the main molecular events triggered by oxidative stress up to the proapoptotic signals that promote the ganglion cell death have been highlighted. The second part of this review, instead, describes some of neuroprotective agents such as polyphenols or polyunsaturated fatty acids as possible therapeutic source against the propagation of glaucomatous damage.

Oil supplementation with a special combination of n-3 and n-6 long-chain polyunsaturated fatty acids does not protect for exercise induced asthma: a double-blind placebo-controlled trial.

BACKGROUND: Many patients suffering from exercise-induced asthma (EIA) have normal lung function at rest and show symptoms and a decline in FEV1 when they do sports or during exercise-challenge. It has been described that long-chain polyunsaturated fatty acids (LCPUFA) could exert a protective effect on EIA. METHODS: In this study the protective effect of supplementation with a special combination of n-3 and n-6 LCPUFA (sc-LCPUFA) (total 1.19 g/ day) were investigated in an EIA cold air provocation model. PRIMARY OUTCOME MEASURE: Decrease in FEV1 after exercise challenge and secondary outcome measure: anti-inflammatory effects monitored by exhaled NO (eNO) before and after sc-LCPUFA supplementation versus placebo. RESULTS: Ninety-nine patients with exercise-induced symptoms aged 10 to 45 were screened by a standardized exercise challenge in a cold air chamber at 4 °C. Seventy-three patients fulfilled the inclusion criteria of a FEV1 decrease > 15% and were treated double-blind placebo-controlled for 4 weeks either with sc-LCPUFA or placebo. Thirty-two patients in each group completed the study. Mean FEV1 decrease after cold air exercise challenge and eNO were unchanged after 4 weeks sc-LCPUFA supplementation. CONCLUSION: Supplementation with sc-LCPUFA at a dose of 1.19 g/d did not have any broncho-protective and anti-inflammatory effects on EIA. TRIAL REGISTRATION: Clinical trial registration number: NCT02410096. Registered 7 February 2015 at Clinicaltrial.gov.

Patterns of Omega-3 and Omega-6 Fatty Acid Dietary Intake and Melanoma Thickness at Diagnosis.

BACKGROUND: Experimental evidence suggests that dietary intakes of omega-3 and omega-6 polyunsaturated fatty acids have divergent effects on melanoma growth, but epidemiologic evidence on their combined effect is lacking. METHODS: In 634 Australian patients with primary melanoma, we assessed prediagnosis consumption of 39 food groups by food frequency questionnaires completed within 2 months of diagnosis. We derived, by reduced rank regression, dietary patterns that explained variability in selected omega-3 and omega-6 fatty acid intakes. Prevalence ratios (PR) and 95% confidence intervals (CI) for the association between tertiles of dietary patterns and melanoma thickness >2 mm versus ≤2 mm were estimated using Poisson regression. RESULTS: Overall omega-3 fatty acid intakes were low. Two major fatty acid dietary patterns were identified: "meat, fish, and fat," positively correlated with intakes of all fatty acids; and "fish, low-meat, and low-fat," positively correlated with long-chain omega-3 fatty acid intake, and inversely with medium-chain omega-3 and omega-6 fatty acid intakes. Prevalence of thick melanomas was significantly higher in those in the highest compared with lowest tertile of the "meat, fish, and fat" pattern (PR, 1.40; 95% CI, 1.01-1.94), especially those with serious comorbidity (PR, 1.83; 95% CI, 1.15-2.92) or a family history (PR, 2.32; 95% CI, 1.00-5.35). The "fish, low-meat, and low-fat" pattern was not associated with melanoma thickness. CONCLUSIONS: People with high meat, fish, and fat intakes, who thus consumed relatively high levels of omega-3 and high omega-6 fatty acid intakes, are more likely to be diagnosed with thick than thin melanomas. IMPACT: High omega-3 and omega-6 fatty acid intakes may contribute to patients' presentation with thick melanomas.

Omega-3 Versus Omega-6 Polyunsaturated Fatty Acids in the Prevention and Treatment of Inflammatory Skin Diseases.

Omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) are nowadays desirable components of oils with special dietary and functional properties. Their therapeutic and health-promoting effects have already been established in various chronic inflammatory and autoimmune diseases through various mechanisms, including modifications in cell membrane lipid composition, gene expression, cellular metabolism, and signal transduction. The application of ω-3 and ω-6 PUFAs in most common skin diseases has been examined in numerous studies, but their results and conclusions were mostly opposing and inconclusive. It seems that combined ω-6, gamma-linolenic acid (GLA), and ω-3 long-chain PUFAs supplementation exhibits the highest potential in diminishing inflammatory processes, which could be beneficial for the management of inflammatory skin diseases, such as atopic dermatitis, psoriasis, and acne. Due to significant population and individually-based genetic variations that impact PUFAs metabolism and associated metabolites, gene expression, and subsequent inflammatory responses, at this point, we could not recommend strict dietary and supplementation strategies for disease prevention and treatment that will be appropriate for all. Well-balanced nutrition and additional anti-inflammatory PUFA-based supplementation should be encouraged in a targeted manner for individuals in need to provide better management of skin diseases but, most importantly, to maintain and improve overall skin health.

Omega-3 and omega-6 polyunsaturated fatty acids for dry eye disease.

BACKGROUND: Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both short- (alpha-linolenic acid [ALA]) and long-chain (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) forms, which largely derive from certain plant- and marine-based foods respectively. Omega-6 PUFAs are present in some vegetable oils, meats, and other animal products. OBJECTIVES: To assess the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) supplements on dry eye signs and symptoms. SEARCH METHODS: CENTRAL, Medline, Embase, two other databases and three trial registries were searched in February 2018, together with reference checking. A top-up search was conducted in October 2019, but the results have not yet been incorporated. SELECTION CRITERIA: We included randomized controlled trials (RCTs) involving dry eye participants, in which omega-3 and/or omega-6 supplements were compared with a placebo/control supplement, artificial tears, or no treatment. We included head-to-head trials comparing different forms or doses of PUFAs. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 34 RCTs, involving 4314 adult participants from 13 countries with dry eye of variable severity and etiology. Follow-up ranged from one to 12 months. Nine (26.5%) studies had published protocols and/or were registered. Over half of studies had high risk of bias in one or more domains. Long-chain omega-3 (EPA and DHA) versus placebo or no treatment (10 RCTs) We found low certainty evidence that there may be little to no reduction in dry eye symptoms with long-chain omega-3 versus placebo (four studies, 677 participants; mean difference [MD] -2.47, 95% confidence interval [CI] -5.14 to 0.19 units). We found moderate certainty evidence for a probable benefit of long-chain omega-3 supplements in increasing aqueous tear production relative to placebo (six studies, 1704 participants; MD 0.68, 95% CI 0.26 to 1.09 mm/5 min using the Schirmer test), although we did not judge this difference to be clinically meaningful. We found low certainty evidence for a possible reduction in tear osmolarity (one study, 54 participants; MD -17.71, 95% CI -28.07 to -7.35 mOsmol/L). Heterogeneity was too substantial to pool data on tear break-up time (TBUT) and adverse effects. Combined omega-3 and omega-6 versus placebo (four RCTs) For symptoms (low certainty) and ocular surface staining (moderate certainty), data from the four included trials could not be meta-analyzed, and thus effects on these outcomes were unclear. For the Schirmer test, we found moderate certainty evidence that there was no intergroup difference (four studies, 455 participants; MD: 0.66, 95% CI -0.45 to 1.77 mm/5 min). There was moderate certainty for a probable improvement in TBUT with the PUFA intervention relative to placebo (four studies, 455 participants; MD 0.55, 95% CI 0.04 to 1.07 seconds). Effects on tear osmolarity and adverse events were unclear, with data only available from a single small study for each outcome. Omega-3 plus conventional therapy versus conventional therapy alone (two RCTs) For omega-3 plus conventional therapy versus conventional therapy alone, we found low certainty evidence suggesting an intergroup difference in symptoms favoring the omega-3 group (two studies, 70 participants; MD -7.16, 95% CI -13.97 to -0.34 OSDI units). Data could not be combined for all other outcomes. Long-chain omega-3 (EPA and DHA) versus omega-6 (five RCTs) For long-chain omega-3 versus omega-6 supplementation, we found moderate certainty evidence for a probable improvement in dry eye symptoms (two studies, 130 participants; MD -11.88, 95% CI -18.85 to -4.92 OSDI units). Meta-analysis was not possible for outcomes relating to ocular surface staining, Schirmer test or TBUT. We found low certainty evidence for a potential improvement in tear osmolarity (one study, 105 participants; MD -11.10, 95% CI -12.15 to -10.05 mOsmol/L). There was low level certainty regarding any potential effect on gastrointestinal side effects (two studies, 91 participants; RR 2.34, 95% CI 0.35 to 15.54). AUTHORS' CONCLUSIONS: Overall, the findings in this review suggest a possible role for long-chain omega-3 supplementation in managing dry eye disease, although the evidence is uncertain and inconsistent. A core outcome set would work toward improving the consistency of reporting and the capacity to synthesize evidence.

Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids.

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.