Photoperiod-Dependent Effects on Blood Biochemical Markers of Phenolic-Enriched Fruit Extracts.

Fruits are rich in bioactive compounds, such as (poly)phenols, and their intake is associated with health benefits, although recent animal studies have suggested that the photoperiod of consumption influences their properties. Fruit loss and waste are critical issues that can be reduced by obtaining functional fruit extracts. Therefore, the aim of this study was to obtain phenolic-enriched extracts from eight seasonal fruits that can modulate blood biochemical parameters and to investigate whether their effects depend on the photoperiod of consumption. Eight ethanol-based extracts were obtained and characterized, and their effects were studied in F344 rats exposed to short (6 h light, L6) and long (18 h light) photoperiods. Cherry and apricot extracts decreased blood triacylglyceride levels only when consumed under the L6 photoperiod. Pomegranate, grape, and orange extracts reduced cholesterol and fasting glucose levels during the L6 photoperiod; however, plum extract reduced fasting glucose levels only during the L18 photoperiod. The results showed the importance of photoperiod consumption in the effectiveness of phenolic-enriched fruit extracts and promising evidence regarding the use of some of the developed fruit extracts as potential functional ingredients for the management of several blood biomarkers.

Milk and Lacticaseibacillus paracasei BL23 effects on intestinal responses in a murine model of colitis.

Probiotic-containing fermented dairy foods have the potential to benefit human health, but the importance of the dairy matrix for efficacy remains unclear. We investigated the capacity of Lacticaseibacillus paracasei BL23 in phosphate-buffered saline (BL23-PBS), BL23-fermented milk (BL23-milk), and milk to modify intestinal and behavioral responses in a dextran sodium sulfate (DSS, 3% wt/vol) mouse model of colitis. Significant sex-dependent differences were found such that female mice exhibited more severe colitis, greater weight loss, and higher mortality rates. Sex differences were also found for ion transport ex vivo, colonic cytokine and tight junction gene expression, and fecal microbiota composition. Measurements of milk and BL23 effects showed BL23-PBS consumption improved weight recovery in females, whereas milk resulted in better body weight recovery in males. Occludin and Claudin-2 gene transcript levels indicated barrier function was impaired in males, but BL23-milk was still found to improve colonic ion transport in those mice. Proinflammatory and anti-inflammatory gene expression levels were increased in both male and female mice fed BL23, and to a more variable extent, milk, compared with controls. The female mouse fecal microbiota contained high proportions of Akkermansia (average of 18.1%) at baseline, and females exhibited more changes in gut microbiota composition following BL23 and milk intake. Male fecal microbiota harbored significantly more Parasutterella and less Blautia and Roseburia after DSS treatment, independent of BL23 or milk consumption. These findings show the complex interplay between dietary components and sex-dependent responses in mitigating inflammation in the digestive tract.NEW & NOTEWORTHY Sex-dependent responses to probiotic Lacticaseibacillus paracasei and milk and the potential of the dairy matrix to enhance probiotic protection against colitis in this context have not been previously explored. Female mice were more sensitive than males to colonic injury, and neither treatment effectively alleviated inflammation in both sexes. These sex-dependent responses may result from differences in the higher baseline proportions of Akkermansia in the gut microbiome of female mice.

Photoperiod-Dependent Effects of Grape-Seed Proanthocyanidins on Adipose Tissue Metabolic Markers in Healthy Rats.

SCOPE: Variations in photoperiod patterns drive metabolic adaptations in mammals, involving important changes in body weight and adiposity. Moreover, (poly)phenols can help heterotrophs adopt metabolic adaptations to face the upcoming environmental conditions. Particularly, proanthocyanidins from grape-seeds show photoperiod-dependent effects on different metabolic parameters. The present study aims to explore whether grape-seed proanthocyanidin extract (GSPE) consumption differently affects the expression of metabolic markers in WAT (subcutaneous and visceral depots) and BAT in a photoperiod-dependent manner. METHODS AND RESULTS: GSPE (25 mg kg-1  day-1 ) is orally administrated for 4 weeks to healthy rats exposed to three photoperiods (L6, L12, and L18). In WAT, GSPE consumption significantly upregulates the expression of lipolytic genes in all photoperiods, being accompanied by increased serum concentrations of glycerol and corticosterone only under the L6 photoperiod. Moreover, adiponectin mRNA levels are significantly upregulated in response to GSPE regardless of the photoperiod, whereas Tnfα and Il6 expression are only downregulated in L6 and L18 photoperiods but not in L12. In BAT, GSPE upregulates Pgc1α expression in all groups, whereas the expression of Pparα is only increased in L18. CONCLUSIONS: The results indicate that GSPE modulates the expression of important metabolic markers of WAT and BAT in a photoperiod-dependent manner.

Administration time effect of dietary proanthocyanidins on the metabolome of Fischer 344 rats is sex- and diet-dependent.

Proanthocyanidins (PAs) are one of the most commonly ingested polyphenols in the human diet, with a wide range of beneficial health effects. Remarkably, PAs have been reported to influence core and peripheral clock genes expression, and their effects may change in a time-of-day dependent manner. Therefore, the aim of this study was to investigate whether the capacity of PAs to modulate the metabolome is conditioned by the time-of-day in which these compounds are consumed in a diet- and sex-dependent manner. To do this, a grape seed proanthocyanidin extract (GSPE) was administered to female and male Fischer 344 rats at ZT0 (in the morning) and ZT12 (at night) and the GSPE administration time effect was evaluated on clock genes expression, melatonin hormone and serum metabolite levels in a healthy and obesogenic context. The results showed an administration time effect of GSPE on the metabolome in a sex and diet-dependent manner. Specifically, there was an effect on amino acid, lipid and cholate metabolite levels that correlated with the central clock genes expression. Therefore, this study shows a strong influence of sex and diet on the PAs effects on the metabolome, modulated in turn by the time-of-day.

Metabolism disturbance by light/dark cycle switching depends on the rat health status: the role of grape seed flavanols.

Changes in light/dark cycles and obesogenic diets are related to the disruption of circadian rhythms and metabolic disorders. Grape seed flavanols have shown beneficial effects on metabolic diseases and, recently, a circadian system modulation has been suggested to mediate their health-enhancing properties. Therefore, the aim of this study was to evaluate the grape seed (poly)phenol extract (GSPE) effects in healthy and obese rats after a light/dark cycle disruption. Forty-eight rats were fed a standard (STD) or cafeteria (CAF) diet for 6 weeks under STD conditions of a light/dark cycle (12 h light per day, L12). Then, animals were switched to a long (18 h light per day, L18) or short (6 h light per day, L6) photoperiod and administered a vehicle (VH) or GSPE (25 mg kg-1) for 1 week. The results showed changes in serum lipids and insulin and metabolomic profiles dependent on the photoperiod and animal health status. GSPE administration improved serum parameters and increased the Nampt gene expression in CAF rats and modified the metabolomic profile in a photoperiod-dependent manner. Metabolic effects of light/dark disturbance depend on the health status of the rats, with diet-induced CAF-induced obese rats being more affected. Grape seed flavanols improve the metabolic status in a photoperiod-dependent manner and their effects on the circadian system suggest that part of their metabolic effects could be mediated by their action on biological rhythms.

Sweet treats before sleep disrupt the clock system and increase metabolic risk markers in healthy rats.

AIM: Biological rhythms are endogenously generated natural cycles that act as pacemakers of different physiological mechanisms and homeostasis in the organism, and whose disruption increases metabolic risk. The circadian rhythm is not only reset by light but it is also regulated by behavioral cues such as timing of food intake. This study investigates whether the chronic consumption of a sweet treat before sleeping can disrupt diurnal rhythmicity and metabolism in healthy rats. METHODS: For this, 32 Fischer rats were administered daily a low dose of sugar (160 mg/kg, equivalent to 2.5 g in humans) as a sweet treat at 8:00 a.m. or 8:00 p.m. (ZT0 and ZT12, respectively) for 4 weeks. To elucidate diurnal rhythmicity of clock gene expression and metabolic parameters, animals were sacrificed at different times, including 1, 7, 13, and 19 h after the last sugar dose (ZT1, ZT7, ZT13, and ZT19). RESULTS: Increased body weight gain and higher cardiometabolic risk were observed when sweet treat was administered at the beginning of the resting period. Moreover, central clock and food intake signaling genes varied depending on snack time. Specifically, the hypothalamic expression of Nampt, Bmal1, Rev-erbα, and Cart showed prominent changes in their diurnal expression pattern, highlighting that sweet treat before bedtime disrupts hypothalamic control of energy homeostasis. CONCLUSIONS: These results show that central clock genes and metabolic effects following a low dose of sugar are strongly time-dependent, causing higher circadian metabolic disruption when it is consumed at the beginning of the resting period, that is, with the late-night snack.

Photoperiod Conditions Modulate Serum Oxylipins Levels in Healthy and Obese Rats: Impact of Proanthocyanidins and Gut Microbiota.

Seasonal rhythms are emerging as a key factor influencing gut microbiota and bioactive compounds functionality as well as several physiological processes such as inflammation. In this regard, their impact on the modulation of oxylipins (OXLs), which are important lipid mediators of inflammatory processes, has not been investigated yet. Hence, we aimed to investigate the effects of photoperiods on OXLs metabolites in healthy and obesogenic conditions. Moreover, we evaluated if the impact of proanthocyanidins and gut microbiota on OXLs metabolism is influenced by photoperiod in obesity. To this purpose, Fischer 344 rats were housed under different photoperiod conditions (L6: 6 h light, L12: 12 h light or L18:18 h light) and fed either a standard chow diet (STD) or a cafeteria diet (CAF) for 9 weeks. During the last 4 weeks, obese rats were daily administered with an antibiotic cocktail (ABX), an oral dose of a grape seed proanthocyanidin extract (GSPE), or with their combination. CAF feeding and ABX treatment affected OXLs in a photoperiod dependent-manner. GSPE significantly altered prostaglandin E2 (PGE2) levels, only under L6 and mitigated ABX-mediated effects only under L18. In conclusion, photoperiods affect OXLs levels influenced by gut microbiota. This is the first time that the effects of photoperiod on OXLs metabolites have been demonstrated.

Gut Microbiota Influences the Photoperiod Effects on Proanthocyanidins Bioavailability in Diet-Induced Obese Rats.

SCOPE: Polyphenols health effects on obesity are mainly attributed to their metabolites generated after their gastrointestinal digestion, in which gut microbiota plays an important role. Moreover, gut microbiota composition and polyphenols bioavailability are influenced by differences in day light length (photoperiod). Thus, this study evaluates if a grape seed proanthocyanidins (GSPEs) extract bioavailability is influenced by different photoperiod exposure via gut microbiota modulation in an obesogenic context. METHODS AND RESULTS: Cafeteria diet-induced obese Fischer 344 rats are housed under different photoperiod conditions (6, 12, or 18 h of light per day) during 9 weeks and administered with GSPE (25 mg kg-1 ) or GSPE and an antibiotic cocktail (ABX) for the last 4 weeks. Serum GSPE-derived metabolites are quantified by HPLC-MS/MS. CONCLUSION: A higher bioavailability is observed under 6 h light/18 h darkness (L6) compared to 18 h light/6 h darkness (L18). Individual metabolites, especially those from the gut microbiota, are affected by photoperiods. ABX treatment alters these photoperiod-mediated changes. Therefore, these results suggest that gut microbiota plays a key role in the photoperiod effects on GSPE bioavailability in obese rats.

Valorization of Chicken Slaughterhouse Byproducts to Obtain Antihypertensive Peptides.

Hypertension (HTN) is the leading cause of premature deaths worldwide and the main preventable risk factor for cardiovascular diseases. Therefore, there is a current need for new therapeutics to manage this condition. In this regard, protein hydrolysates containing antihypertensive bioactive peptides are of increasing interest. Thus, agri-food industry byproducts have emerged as a valuable source to obtain these hydrolysates as they are rich in proteins and inexpensive. Among these, byproducts from animal origin stand out as they are abundantly generated worldwide. Hence, this review is focused on evaluating the potential role of chicken slaughterhouse byproducts as a source of peptides for managing HTN. Several of these byproducts such as blood, bones, skins, and especially, chicken feet have been used to obtain protein hydrolysates with angiotensin-converting enzyme (ACE)-inhibitory activity and blood pressure-lowering effects. An increase in levels of endogenous antioxidant compounds, a reduction in ACE activity, and an improvement of HTN-associated endothelial dysfunction were the mechanisms underlying their effects. However, most of these studies were carried out in animal models, and further clinical studies are needed in order to confirm these antihypertensive properties. This would increase the value of these byproducts, contributing to the circular economy model of slaughterhouses.

Winery by-products as a valuable source for natural antihypertensive agents.

Hypertension (HTN) is one of the leading causes of death in the world. Agri-food by-products are emerging as a novel source of natural antihypertensive agents allowing for their valorization and making food and agricultural industries more environmentally friendly. In this regard, wine making process generates large amounts of by-products rich in phenolic compounds that have shown potential to exert several beneficial effects including antihypertensive properties. The aim of this study was to review the blood pressure-lowering effects of winery by-products. In addition, molecular mechanisms involved in their bioactivity were also evaluated. Among the winery by-products, grape seed extracts have widely shown antihypertensive properties in both animal and human studies. Moreover, recent evidence suggests that grape stem, skin and pomace and wine lees may also have great potential to manage HTN, although more studies are needed in order to confirm their potential in humans. Improvement of endothelial dysfunction and reduction of oxidative stress associated with HTN are the main mechanisms involved in the blood pressure-lowering effects of these by-products.

Fatty acid metabolism in liver and muscle is strongly modulated by photoperiod in Fischer 344 rats.

Circadian and seasonal variations produce variations in physiological processes throughout the day and the year, respectively. In this sense, both the light and the moment of feeding are strong modulators of the central and peripheral clocks. However, little is known about its influence on certain metabolic parameters and on the composition of liver and muscle fatty acids (FA). In the present study, 24 Fischer 344 rats were exposed for 11 weeks to different photoperiods, L6, L12 and L18, with 6, 12 and 18 h of light/day, respectively. They were fed a standard diet. Serum metabolic parameters, gene expression of liver enzymes and gastrocnemius muscle involved in the synthesis, elongation, desaturation and ß-oxidation of FA were analyzed. We have found that exposure to different hours of light has a clear effect on FA composition and gene expression in the liver. Mainly, the biosynthesis of unsaturated FA was altered in the L18 animals with respect to those exposed to L12, while the L6 did not show significant changes. At the muscle level, differences were observed in the concentration of mono and polyunsaturated FA. A multivariate analysis confirmed the differences between L12 and L18 in a significant way. We conclude that exposure to long days produces changes in the composition of liver and muscle FA, as well as changes in the gene expression of oxidative enzymes compared to exposure to L12, which could be a consequence of different seasonal eating patterns.

The effects of grape seed proanthocyanidins in cafeteria diet-induced obese Fischer 344 rats are influenced by faecal microbiota in a photoperiod dependent manner.

Polyphenols are of high interest due to their beneficial health effects, including anti-obesity properties. The gut microbiota may play an important role in polyphenol-mediated effects as these bacteria are significantly involved in the metabolism of polyphenols. Moreover, seasonal rhythms have been demonstrated to influence both the gut microbiota composition and polyphenol bioavailability. Thus, the goal of this study was to evaluate the impact of photoperiods and microbiota on polyphenol functionality in an obesogenic context. Towards this aim, cafeteria diet-fed Fischer 344 rats were housed under three different photoperiod conditions (L6: 6 h of light, L12: 12 h of light and L18: 18 h of light) for 9 weeks. During the last 4 weeks of the experiment, rats were daily administered with an oral dose of a grape seed proanthocyanidin extract (GSPE) (25 mg per kg body weight). Additionally, rats treated with GSPE and an antibiotic cocktail (ABX) in their drinking water were included for a better understanding of the gut microbiota role in GSPE functionality. Vehicle and non-ABX treated rats were included as controls. GSPE decreased body weight gain and fat depots only under L18 conditions. Interestingly, the gut microbiota composition was strongly altered in this photoperiod. GSPE + ABX-treated rats gained significantly less body weight compared to the rats of the rest of the treatments under L18 conditions. These results suggest that GSPE functionality is modulated by the gut microbiota in a photoperiod dependent manner. These novel findings corroborate seasonal rhythms as key factors that must be taken into account when investigating the effects of polyphenols in the treatment or prevention of chronic diseases.

Gut Seasons: Photoperiod Effects on Fecal Microbiota in Healthy and Cafeteria-Induced Obese Fisher 344 Rats.

Gut microbiota and biological rhythms are emerging as key factors in the modulation of several physiological and metabolic processes. However, little is known about their interaction and how this may affect host physiology and metabolism. Several studies have shown oscillations of gut microbiota that follows a circadian rhythmicity, but, in contrast, variations due to seasonal rhythms have not been sufficiently investigated yet. Thus, the goal of this study was to investigate the impact of different photoperiods, which mimic seasonal changes, on fecal microbiota composition and how this interaction affects diet-induced obesity development. To this aim, Fisher 344 male rats were housed under three photoperiods (L6, L12 and L18) and fed with standard chow diet or cafeteria diet (CAF) for 9 weeks. The 16S ribosomal sequencing of collected fecal samples was performed. The photoperiod exposure significantly altered the fecal microbiota composition under L18, especially in CAF-fed rats. Moreover, these alterations were associated with changes in body weight gain and different fat parameters. These findings suggest a clear impact of seasonal rhythms on gut microbiota, which ultimately translates into different susceptibilities to diet-induced obesity development. This is the first time to our knowledge that the photoperiod impact on gut microbiota composition has been described in an obesity context although further studies are needed in order to elucidate the mechanisms involved.

Cardioprotective Properties of Phenolic Compounds: A Role for Biological Rhythms.

Cardiovascular diseases (CVD) are the leading cause of deaths worldwide and their prevalence is continuously increasing. Available treatments may present several side effects and therefore the development of new safer therapeutics is of interest. Phenolic compounds have shown several cardioprotective properties helpful in reducing different CVD risk factors such as inflammation, elevated blood pressure, hyperlipidemia, or endothelial dysfunction. These factors are significantly influenced by biological rhythms which are in fact emerging as key modulators of important metabolic and physiological processes. Thus, increased events of CVD have been observed under circadian rhythm disruption or in winter versus other seasons. These rhythms can also affect the functionality of phenolic compounds. Indeed, different effects have been observed depending on the administration time or under different photoperiods. Therefore, in this review the focus will be on the potential of phenolic compounds as therapeutics to prevent CVD via biological rhythm modulation.

Identification of novel antihypertensive peptides from wine lees hydrolysate.

Enzymatic-assisted extraction using Flavourzyme® has been demonstrated to be a useful methodology to obtain wine lees (WL) enriched in phenolic compounds and with enhanced antihypertensive activity. Nevertheless, taking into account that Flavourzyme® possess proteolytic activity, the release of bioactive peptides should not be ruled out. In this study, we investigate the presence of antihypertensive peptides in the WL hydrolysate. Peptides were separated into fractions by ultrafiltration and RP-HPLC. Next, peptide identification by nano-HPLC-(Orbitrap)MS/MS was performed in the fractions showing the highest angiotensin-converting enzyme inhibitory (ACEi) activities. Six peptides were identified; three of them showing ACEi (IC50) values lower than 20 µM. The peptide antihypertensive effect was evaluated in spontaneously hypertensive rats at an oral dose of 10 mg/kg bw. Peptides FKTTDQQTRTTVA, NPKLVTIV, TVTNPARIA, LDSPSEGRAPG and LDSPSEGRAPGAD exhibited antihypertensive activity, confirming that they could contribute to the blood pressure-lowering effect of the WL hydrolysate. These peptides have a great potential as functional ingredients to manage hypertension.

Administration Time Significantly Affects Plasma Bioavailability of Grape Seed Proanthocyanidins Extract in Healthy and Obese Fischer 344 Rats.

SCOPE: Phenolic compounds are bioactive molecules that are associated with several health benefits. Metabolization and absorption are the main determinants of their bioavailability and bioactivity. Thus, the study of the factors that modulate these processes, such as sex or diet is essential. Recently, it has been shown that biological rhythms may also play a key role. Hence, the aim of this study is to evaluate if the bioavailability of a grape proanthocyanidin extract (GSPE) is affected by the administration time in an animal model of metabolic syndrome (MetS). METHODS AND RESULTS: Female and male Fischer 344 rats are fed either a standard or a cafeteria diet (CAF) for 9 weeks, and an oral dose of GSPE (25 mg kg-1 ) is daily administered either at 8:00 am (zeitgeber time (ZT)-0) or at 8:00 pm (ZT-12) during the last 4 weeks. Plasma phenolic compounds are then quantified by liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Phase-II and gut microbiota-derived phenolic metabolites are affected by ZT in all conditions or only in obese rats, respectively. CAF feeding affected the bioavailability of phenolic acids and free flavan-3-ols. Differences due to sex are also observed. CONCLUSION: These findings demonstrate that ZT, diet, and sex are key factors influencing phenolic compounds bioavailability.

Chronic Effect of a Cafeteria Diet and Intensity of Resistance Training on the Circulating Lysophospholipidome in Young Rats.

The daily practice of physical exercise and a balanced diet are recommended to prevent metabolic syndrome (MetS). As MetS is a multifactorial disorder associated with the development of serious diseases, the advancement of comprehensive biomarkers could aid in an accurate diagnosis. In this regard, it is known that gut microbiota is altered in MetS, and especially, lipid metabolites species are highly modified, thus emerging as potential biomarkers. In preliminary studies, we observed that alterations in serum lysoglycerophospholipids (Lyso-PLs) were shared between animals with diet-induced MetS and those performing resistance exercises assiduously. Therefore, our objective was the targeted determination of the lysophospholipidome in young rats fed a standard (ST) or a cafeteria diet (CAF) and submitted to different training intensities to evaluate its potential as a biomarker of a detrimental lifestyle. Targeted metabolomics focused on lysophosphatidylcholines (Lyso-PCs) and lysophosphatidylethanolamines (Lyso-PEs) and multivariate statistics were used to achieve an integral understanding. Chronic intake of CAF altered the serological levels of both lipid subclasses. Twenty-two Lyso-PLs were significantly altered by CAF, from which we selected Lyso-PCs (14:0), (17:1) and (20:2) and Lyso-PEs (18:2) and (18:3) as they were enough to achieve an optimal prediction. The main effect of physical training was decreased Lyso-PEs levels with disparities among training intensities for each diet. We concluded that an examination of the lysophospholipidome reveals the general state of the metabolome in young female rats, especially due to intake of an MetS-inducing diet, thus highlighting the importance of this family of compounds in lipid disorders.

Enzyme-Assisted Extraction to Obtain Phenolic-Enriched Wine Lees with Enhanced Bioactivity in Hypertensive Rats.

The antihypertensive effect of the soluble fraction of wine lees (WL) from Cabernet variety grapes was recently reported by our group. This blood pressure (BP)-lowering effect was attributed to the presence of flavanols and anthocyanins. In this context, phenolic-enriched wine lees (PWL) could potentially exhibit a stronger bioactivity. Therefore, the aim of this study was to obtain a soluble fraction of WL with increased phenolic content and evaluate its functionality. The PWL were obtained using an enzyme-assisted extraction based on the hydrolysis of WL proteins with Flavourzyme®. They contained 57.20% more total phenolic compounds than WL, with anthocyanins and flavanols being the largest families present. In addition, PWL also showed greater angiotensin-converting enzyme inhibitory and antioxidant activities. Finally, the antihypertensive activity of the PWL was evaluated in spontaneously hypertensive rats. A single dose of 5 mL/kg body weight of PWL showed a greater BP-lowering effect than the one shown by WL. Moreover, this antihypertensive effect was more prolonged than the one produced by the antihypertensive drug Captopril. These results demonstrate that enzymatic protein hydrolysis is a useful method to maximize the extraction of phenolic compounds from WL and to obtain extracts with enhanced functionalities.

Impact of gut microbiota on plasma oxylipins profile under healthy and obesogenic conditions.

BACKGROUND & AIMS: Oxylipins (OXLs) are bioactive lipid metabolites derived from polyunsaturated fatty acids (PUFAs) which act as signaling molecules and are involved in inflammatory processes such as those that occur in obesity. On the other hand, gut microbiota plays an essential role in regulating inflammatory responses. However, little is known about the potential impact of gut bacteria on OXLs metabolism. Thus, the objective of this study was to investigate the effect of gut microbiota dysbiosis on plasma oxylipins profile in healthy and diet-induced obese animals. METHODS: Eight-week-old male Wistar rats were fed with either a standard or cafeteria diet (CAF) for 5 weeks and administered an antibiotic cocktail (ABX) in the drinking water (Ampicillin: 1 g/ml, Vancomycin: 0.5 g/ml, Imipenem: 0.25 g/ml) for the last 2 weeks in order to induce gut microbiota dysbiosis. Metabolomics analysis of OXLs in plasma was performed by HPLC-MS analysis. No antibiotic treated animals were included as controls. RESULTS: Plasma OXLs profile was significantly altered due to both CAF feeding and ABX administration. ABX effect was more pronounced under obesogenic conditions. Several significant correlations between different bacteria taxa and these lipid mediators were observed. Among these, the positive correlation of Proteobacteria with LTB4, a proinflammatory OXL involved in obesity-related disorders, was especially remarkable. CONCLUSIONS: Gut microbiota plays a key role in regulating these lipid metabolites and, therefore, affecting oxylipins-mediated inflammatory processes. These results are the first evidence to our knowledge of gut microbiota impact on OXLs metabolism. Moreover, this can set the basis for developing new obesity markers based on OXLs and gut microbiota profiles.