Comparison of Experimental Methodologies Based on Bulk-Metagenome and Virus-like Particle Enrichment: Pros and Cons for Representativeness and Reproducibility in the Study of the Fecal Human Virome.

Studies on the human virome based on the application of metagenomic approaches involve overcoming a series of challenges and limitations inherent not only to the biological features of viruses, but also to methodological pitfalls which different approaches have tried to minimize. These approaches fall into two main categories: bulk-metagenomes and virus-like particle (VLP) enrichment. In order to address issues associated with commonly used experimental procedures to assess the degree of reliability, representativeness, and reproducibility, we designed a comparative analysis applied to three experimental protocols, one based on bulk-metagenomes and two based on VLP enrichment. These protocols were applied to stool samples from 10 adult participants, including two replicas per protocol and subject. We evaluated the performances of the three methods, not only through the analysis of the resulting composition, abundance, and diversity of the virome via taxonomical classification and type of molecule (DNA versus RNA, single stranded vs. double stranded), but also according to how the a priori identical replicas differed from each other according to the extraction methods used. Our results highlight the strengths and weaknesses of each approach, offering valuable insights and tailored recommendations for drawing reliable conclusions based on specific research goals.

The Non-Dereliction in Evolution: Trophic Specialisation Drives Convergence in the Radiation of Red Devil Spiders (Araneae: Dysderidae) in the Canary Islands.

Natural selection plays a key role in deterministic evolution, as clearly illustrated by the multiple cases of repeated evolution of ecomorphological characters observed in adaptive radiations. Unlike most spiders, Dysdera species display a high variability of cheliceral morphologies, which has been suggested to reflect different levels of specialization to feed on isopods. In this study, we integrate geometric morphometrics and experimental trials with a fully resolved phylogeny of the highly diverse endemic species from the Canary Islands to 1) quantitatively delimit the different cheliceral morphotypes present in the archipelago, 2) test their association with trophic specialization, as reported for continental species, 3) reconstruct the evolution of these ecomorphs throughout the diversification of the group, 4) test the hypothesis of convergent evolution of the different morphotypes, and 5) examine whether specialization constitutes a case of evolutionary irreversibility in this group. We show the existence of 9 cheliceral morphotypes and uncovered their significance for trophic ecology. Further, we demonstrate that similar ecomorphs evolved multiple times in the archipelago, providing a novel study system to explain how convergent evolution and irreversibility due to specialization may be combined to shape phenotypic diversification in adaptive radiations.

Almond (Prunus dulcis) Bagasse as a Source of Bioactive Compounds with Antioxidant Properties: An In Vitro Assessment.

The presence of components of nutritional interest makes fresh almond bagasse an interesting by-product for obtaining functional ingredients. Stabilization through a dehydration process is an interesting option for its integral use, ensuring its conservation and management. Subsequently, it can be turned into powder, facilitating its use as an ingredient. The aim of this paper was to determine the effects of hot air drying at 60 and 70 °C and lyophilization on the release of phenolic components and antiradical capacity in in vitro gastrointestinal digestion and colonic fermentation, as well as on growing microbiota composition by applying high throughput sequencing. The novelty of this study lies in this holistic approach; considering both technological and physiological aspects related to gastrointestinal digestion and colonic fermentation will provide the best conditions for functional foods. The results obtained showed that lyophilization provides a powder with a total phenol content and antiradical capacity higher than hot air drying. Furthermore, in dehydrated samples, both in vitro digestion and colonic fermentation revealed a phenol content and anti-radical capacity superior to those existing in undigested products. In addition, after colonic fermentation, beneficial bacteria species have been identified. Obtaining powders from almond bagasse is presented as an interesting opportunity for the valorization of this by-product.

Dispersal ability and niche breadth influence interspecific variation in spider abundance and occupancy.

The relationship between species local abundance and their regional distribution (occupancy) is one of the most extensively recognized and investigated patterns in ecology. While exceptions exist, the generally held model is that locally abundant species also tend to be more widespread geographically. However, there is only a limited understanding of both the mechanisms driving this relationship, and their scale dependency. Here we use occupancy and abundance data for 123 species of spider from across the Canary Islands to understand how both dispersal ability and niche breadth might mediate variation among species for local abundance and occupancy. We test the predictions that (i) dispersal ability explains variation among species for both abundance and occupancy, and (ii) species with a higher degree of habitat specialization, reflecting more limited niche breadth, will have both higher occupancy and abundance. We find no evidence within habitat patches for an effect of dispersal ability on either local abundance or site occupancy, while across all patches species with higher dispersal ability tend to occupy more sites. Species largely restricted to laurel forests have higher abundance than species with broader niche breadth, but similar occupancy. The study revealed that dispersal ability and niche breadth were significant predictors of the abundance-occupancy relationship, highlighting the importance of both factors for understanding patterns of abundance and occupancy among spider species.

BAY-6096: A Potent, Selective, and Highly Water-Soluble Adrenergic α2B Antagonist.

After acute myocardial infarction, early reperfusion is the most effective strategy for reducing cardiac damage and improving clinical outcome. However, restoring blood flow to the ischemic myocardium can paradoxically induce injury by itself (reperfusion injury), with microvascular dysfunction being one contributing factor. α2B adrenergic receptors have been hypothesized to be involved in this process. To assess α2B-related pharmacology, we identified a novel α2B antagonist by HTS. The HTS hit showed limited α2A selectivity as well as low solubility and was optimized toward BAY-6096, a potent, selective, and highly water-soluble α2B antagonist. Key aspects of the optimization were the introduction of a permanently charged pyridinium moiety to achieve very good aqueous solubility and the inversion of an amide to prevent genotoxicity. BAY-6096 dose-dependently reduced blood pressure increases in rats induced by an α2B agonist, demonstrating the role of α2B receptors in vascular constriction in rats.

How much biodiversity is concealed in the word 'biodiversity'?

Amidst a global biodiversity crisis1, the word 'biodiversity' has become indispensable for conservation and management2. Yet, biodiversity is often used as a buzzword in scientific literature. Resonant titles of papers claiming to have studied 'global biodiversity' may be used to promote research focused on a few taxonomic groups, habitats, or facets of biodiversity - taxonomic, (phylo)genetic, or functional. This usage may lead to extrapolating results outside the target systems of these studies with direct consequences for our understanding of life on Earth and its practical conservation. Here, we used a random sample of papers with the word 'biodiversity' in their title to take a long view of the use of this term. Despite improvements in analytical tools, monitoring technologies, and data availability3,4, we found that the taxonomic scope of research articles has not increased in recent years. We also show that studies with a wider taxonomic scope attract more citations and online attention. Our results have broad ramifications for understanding how extrapolating from studies with narrow taxonomic scope affects our view of global biodiversity and conservation.

La formación de grupos en Educación Física. Una revisión de la literatura / Picking teams in Physical Education. A literature review

La formación de grupos en Educación Física parece perpetuarse como un proceso desatendido, reproducido automáticamente e irreflexivo. Así al menos se desprende de la escasísima literatura en español al respecto. Por ello, los objetivos de este artículo pasan por explicitar el estado de la cuestión, problematizando la formación de grupos y aflorando el currículo oculto que este proceder contiene. Para ello, se ha llevado a cabo una revisión de la literatura en las bases de datos Dialnet y Web of Science y completada posteriormente de forma manual. Los términos de búsqueda han sido ‘formación de grupos’ o ‘agrupamientos’ y ‘Educación Física’, y en inglés los vocablos ‘the formation of groups’ o ‘picking teams’ y ‘Physical Education’. Los resultados de la misma son escasos pues arrojan 4 estudios encontrados en las bases de datos, a los que manualmente se les han añadido otros 26, lo que confirma la desatención académica de este proceder. Además, los documentos constatan efectos negativos y recurrentes sobre todo en el alumnado menos hábil y en muchas de las alumnas. Sin embargo, se explicitan algunas propuestas que, entre otras cosas, relativizan la estigmatización y se acercan a los postulados de la justicia social. (AU)

Picking teams in Physical Education seems to perpetuate itself as a neglected, automatically reproduced, and thoughtless process. So at least it is clear from the very scarce literature in Spanish on the matter. Therefore, the aims of this article are to put the state of the art on the table, problematizing picking teams and surfacing the hidden curriculum that this procedure contains. For this, a review of the literature has been carried out in Dialnet and Web of Science databases and completed manually. The search terms have been ‘formación de grupos’ or ‘agrupamientos’ and ‘Educación Física’ in Spanish, and in English the words ‘the formation of groups’ or ‘picking teams’ and ‘Physical Education’. The few results of the search shows only 4 studies, included in the present review, and 26 studies have been manually added, confirm the academic neglect of this procedure. In addition, the documents confirm negative and recurring effects, especially in the less skilled students and in many of the female students. However, some proposals are made explicit that, among other things, relativize stigmatization and come closer to the postulates of social justice. (AU)

Effects of different foods and cooking methods on the gut microbiota: an in vitro approach.

To support personalized diets targeting the gut microbiota, we employed an in vitro digestion-fermentation model and 16S rRNA gene sequencing to analyze the microbiota growing on representative foods of the Mediterranean and Western diets, as well as the influence of cooking methods. Plant- and animal-derived foods had significantly different impacts on the abundances of bacterial taxa. Animal and vegetable fats, fish and dairy products led to increases in many taxa, mainly within the Lachnospiraceae. In particular, fats favored increases in the beneficial bacteria Faecalibacterium, Blautia, and Roseburia. However, butter, as well as gouda cheese and fish, also resulted in the increase of Lachnoclostridium, associated to several diseases. Frying and boiling produced the most distinct effects on the microbiota, with members of the Lachnospiraceae and Ruminococcaceae responding the most to the cooking method employed. Nevertheless, cooking effects were highly individualized and food-dependent, challenging the investigation of their role in personalized diets.

Effect of the addition of 4OHE2 and quercetin in culture media on ROS levels and gene expression in mouse blastocysts.

AIMS: The main objective of this work is to elucidate whether Quercetin (Qc) and 4-Hidroxistradiol (4OHE2 ) decrease the level of reactive oxygen species (ROS) in in vitro obtained embryos and to analyse which genes are activated under the treatments that could explain this improvement. METHODS: Oxidative stress was induced during embryo culture by H2 O2 treatment and ROS production was measured and compared with embryos treated with Qc or 4OHE2 . Gene expression was analysed by Q-PCR in control embryos obtained in utero (IU) or by IVF and compared with the levels found in embryos cultured with Qc or 4OHE2 to determine the effect of these compounds. KEY RESULTS: Qc strongly reduces ROS levels in embryos after a treatment of 4h. On the contrary, 4OHE2 had no effect in reducing ROS levels in embryos. The addition of these molecules to the culture media upregulate several hypoxia-related genes when Qc is added to the culture media, and implantation-related genes when 4OHE2 is used. CONCLUSIONS: Qc is a very strong antioxidant molecule that when used for short periods of time during culture can reduce ROS levels and improve embryo quality by activating antioxidant enzymes. 4OHE2 supplementation, despite having no effects in reducing ROS levels, acts directly in the molecular signalling implicated in the implantation process and could be also considered as a supplement for embryo culture during IVF. IMPLICATIONS: Proper supplementation of the culture media could greatly improve the quality of embryos cultured in vitro , resulting in better results in IVF clinics.

Nutritional Supplementation to Increase Influenza Vaccine Response in Children Living With HIV: A Pilot Clinical Trial.

Aims: Vaccine response is poor among children living with HIV. The gut microbiota has been identified as a potential target to improve vaccine immunogenicity, but data are scarce in the context of HIV infection. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected children were randomized to receive a mixture of symbiotics, omega-3/6 fatty acids, and amino acids or placebo for 4 weeks, each in combination with ART, and were then immunized against influenza. Vaccine response and safety of the nutritional supplementation were the primary outcomes. Results: Eighteen HIV-infected children completed the follow-up period (mean age 11.5 ± 4.14 years, 61% female). The nutritional supplement was safe but did not enhance the response to the influenza vaccine. A 4-fold rise in antibody titers was obtained in only 37.5% of participants in the intervention arm vs. 40% in the placebo. No immunological or inflammatory predictors of vaccine response were identified. Conclusions: In this exploratory study, a 4-week course of symbiotics did not increase influenza vaccine immunogenicity in HIV-infected children. Larger studies are warranted to address the potential of modulating the microbiome in children living with HIV.

Interactions among the mycobiome, bacteriome, inflammation, and diet in people living with HIV.

While the intestinal microbiome seems a major driver of persistent immune defects in people with HIV (PWH), little is known about its fungal component, the mycobiome. We assessed the inter-kingdom mycobiome-bacteriome interactions, the impact of diet, and the association with the innate and adaptive immunity in PWH on antiretroviral therapy. We included 24 PWH individuals and 12 healthy controls. We sequenced the Internal Transcribed Spacer 2 amplicons, determined amplicon sequence variants, measured biomarkers of the innate and adaptive immunity in blood and relations with diet. Compared to healthy controls, PWH subjects exhibited a distinct and richer mycobiome and an enrichment for Debaryomyces hansenii, Candida albicans, and Candida parapsilosis. In PWH, Candida and Pichia species were strongly correlated with several bacterial genera, including Faecalibacterium genus. Regarding the links between the mycobiome and systemic immunology, we found a positive correlation between Candida species and the levels of proinflammatory cytokines (sTNF-R2 and IL-17), interleukin 22 (a cytokine implicated in the regulation of mucosal immunity), and CD8+ T cell counts. This suggests an important role of the yeasts in systemic innate and adaptive immune responses. Finally, we identified inter-kingdom interactions implicated in fiber degradation, short-chain fatty acid production, and lipid metabolism, and an effect of vegetable and fiber intake on the mycobiome. Therefore, despite the great differences in abundance and diversity between the bacterial and fungal communities of the gut, we defined the changes associated with HIV, determined several different inter-kingdom associations, and found links between the mycobiome, nutrient metabolism, and systemic immunity.

Evaluation of the Effects of a Short Supplementation With Tannins on the Gut Microbiota of Healthy Subjects.

Western diet, high in fats and sugars and low in greens, contributes to dysbiosis of the gut microbiota, which can lead to a variety of chronic diseases related with inflammation. Supplementation with bioactive compounds can help to maintain a healthy eubiotic state. Thus, we performed a 4-weeks nutritional intervention on healthy volunteers to investigate whether a blend of natural tannin extracts could induce healthy changes in the microbial intestinal ecosystem. Changes in the composition and functionality of the microbiota could be observed from the first two weeks onward. 16S rRNA amplicon next-generation sequencing (NGS) revealed a significant increase in microbial diversity at the end of the intervention, as well as trends toward increases in the relative abundances of several beneficial taxa, such as Ruminococcus bicirculans, Faecalibacterium prausnitzii, Lachnospiraceae UCG 010, Lachnospiraceae NK4A136, Bacteroides thetaiotaomicron and B. uniformis. Remarkably, some of the identified taxa were also identified as responsible for an increase in the production of short-chain fatty acids (SCFAs), microbial metabolites that contribute to the modulation of the immune system and have various other anti-inflammatory functions in the gut. Taken together, these results suggest that the tannin supplementation could exert a prebiotic effect by selectively stimulating the growth and the activity of bacteria that are advantageous for the host.

Global response of conservationists across mass media likely constrained bat persecution due to COVID-19.

Most people lack direct experience with wildlife and form their risk perception primarily on information provided by the media. The way the media frames news may substantially shape public risk perception, promoting or discouraging public tolerance towards wildlife. At the onset of the COVID-19 pandemic, bats were suggested as the most plausible reservoir of the virus, and this became a recurrent topic in media reports, potentially strengthening a negative view of this ecologically important group. We investigated how media framed bats and bat-associated diseases before and during the COVID-19 pandemic by assessing the content of 2651 online reports published across 26 countries, to understand how and how quickly worldwide media may have affected the perception of bats. We show that the overabundance of poorly contextualized reports on bat-associated diseases likely increased the persecution towards bats immediately after the COVID-19 outbreak. However, the subsequent interventions of different conservation communication initiatives allowed pro-conservation messages to resonate across the global media, likely stemming an increase in bat persecution. Our results highlight the modus operandi of the global media regarding topical biodiversity issues, which has broad implications for species conservation. Knowing how the media acts is pivotal for anticipating the propagation of (mis)information and negative feelings towards wildlife. Working together with journalists by engaging in dialogue and exchanging experiences should be central in future conservation management.

A Circular Economy Approach to Restoring Soil Substrate Ameliorated by Sewage Sludge with Amendments.

This study examined the use of an artificial soil substrate in a mine waste reclamation area and its effect on plant metabolic functions. Research was conducted by determining the relationship between the plants' biochemical features and the properties of plant growth medium derived from post-flotation coal waste, sewage sludge, crushed stone and fly ash on the surface of the mine waste disposal area. Trees and shrubs were established on the material and allowed to grow for eight years. The study determined that the applied plants and the naturally occurring Taraxacum officinale were suitable for physio-biochemical assessment, identification of derelict areas and reclamation purposes. An evaluation of a soil substrate applied to post-mining areas indicated that it was beneficial for plant growth since it activated the metabolic functions of herbaceous plants, shrubs, and trees. The study showed that soil substrate can be targeted to improve plant stress tolerance to potentially toxic elements (PTEs). These data suggest the potential for growth and slower susceptible response to Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn. It is possible that the constructed soil-substitute substrate (biosolid material) would be an effective reclamation treatment in areas where natural soil materials are polluted by PTEs. This observation may reflect a more efficient use of soil substrate released from the cycling of organic biogene pools, in accordance with the circular economy approach. In further studies related to land reclamation using sewage sludge amendments, it would be necessary to extend the research to other stress factors, such as salinity or water deficiency.

Targeting the Gut Microbiota of Vertically HIV-Infected Children to Decrease Inflammation and Immunoactivation: A Pilot Clinical Trial.

Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional supplementation are unclear. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected on ART were randomized to supplementation with a daily mixture of symbiotics, omega-3/6 fatty acids and amino acids, or placebo four weeks, in combination with ART. We analyzed inflammatory markers and T-cell activation changes and their correlations with shifts in fecal microbiota. Results: Twenty-four HIV-infected children were recruited and randomized to receive a symbiotic nutritional supplement or placebo. Mean age was 12 ± 3.9 years, 62.5% were female. All were on ART and had HIV RNA < 50/mL. We did not detect changes in inflammatory (IL-6, IL-7, IP-10), microbial translocation (sCD14), mucosal integrity markers (IFABP, zonulin) or the kynurenine to tryptophan ratio, or changes in markers of the adaptive immune response in relation to the intervention. However, we found correlations between several key bacteria and the assessed inflammatory and immunological parameters, supporting a role of the microbiota in immune modulation in children with HIV. Conclusions: In this exploratory study, a four-week nutritional supplementation had no significant effects in terms of decreasing inflammation, microbial translocation, or T-cell activation in HIV-infected children. However, the correlations found support the interaction between gut microbiota and the immune system.

Pulmonary hypertension in adults with congenital heart disease. Clinical phenotypes and outcomes in the advanced pulmonary vasodilator era.

BACKGROUND: Mortality of pulmonary hypertension associated with congenital heart disease (PAH-CHD) in adults remains high. OBJECTIVES: To identify predictors of death and to assess the impact of treatment on outcome. METHODS: Retrospective, multicenter cohort study of 103 adults with PAH-CHD followed-up for 8.6 ± 4.6 years. Patients were grouped according to underlying shunt type into pre-tricuspid, post-tricuspid and complex. Survival rates were analyzed and predictors of death were investigated with Cox regression models. RESULTS: In the post-tricuspid and complex groups (38 and 37 patients, respectively), the most common clinical PAH-CHD subgroup was Eisenmenger syndrome (76.3% and 59.5%, respectively) whereas, in the pre-tricuspid group (28 patients), 46.5% of patients had small or corrected defects. Overall, 88 patients received vasodilators; 39% required combination-therapy. Overall survival at 10 years was 65%. Mortality was highest in the pre-tricuspid group, FC-III-IV and amongst patients receiving monotherapy (p < 0.050). On multivariate analysis, predictors of poor outcome were pericardial effusion (HR: 4,520 [1,470-13,890]; p = 0,008), oxygen saturation(HR: 0.940 [0,900 - 0,990]; p = 0,018) and genetic syndromes(HR: 3,280 [1,098-9,780]; p = 0,033). CONCLUSIONS: Patients in advanced stages at initiation of treatment were at high risk of death and strong consideration should be given for more aggressive therapy.

The World Spider Trait database: a centralized global open repository for curated data on spider traits.

Spiders are a highly diversified group of arthropods and play an important role in terrestrial ecosystems as ubiquitous predators, which makes them a suitable group to test a variety of eco-evolutionary hypotheses. For this purpose, knowledge of a diverse range of species traits is required. Until now, data on spider traits have been scattered across thousands of publications produced for over two centuries and written in diverse languages. To facilitate access to such data, we developed an online database for archiving and accessing spider traits at a global scale. The database has been designed to accommodate a great variety of traits (e.g. ecological, behavioural and morphological) measured at individual, species or higher taxonomic levels. Records are accompanied by extensive metadata (e.g. location and method). The database is curated by an expert team, regularly updated and open to any user. A future goal of the growing database is to include all published and unpublished data on spider traits provided by experts worldwide and to facilitate broad cross-taxon assays in functional ecology and comparative biology. Database URL:https://spidertraits.sci.muni.cz/.

An extended reconstruction of human gut microbiota metabolism of dietary compounds.

Understanding how diet and gut microbiota interact in the context of human health is a key question in personalized nutrition. Genome-scale metabolic networks and constraint-based modeling approaches are promising to systematically address this complex problem. However, when applied to nutritional questions, a major issue in existing reconstructions is the limited information about compounds in the diet that are metabolized by the gut microbiota. Here, we present AGREDA, an extended reconstruction of diet metabolism in the human gut microbiota. AGREDA adds the degradation pathways of 209 compounds present in the human diet, mainly phenolic compounds, a family of metabolites highly relevant for human health and nutrition. We show that AGREDA outperforms existing reconstructions in predicting diet-specific output metabolites from the gut microbiota. Using 16S rRNA gene sequencing data of faecal samples from Spanish children representing different clinical conditions, we illustrate the potential of AGREDA to establish relevant metabolic interactions between diet and gut microbiota.

Gut Microbiota Profile and Its Association with Clinical Variables and Dietary Intake in Overweight/Obese and Lean Subjects: A Cross-Sectional Study.

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.

Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor-beta-induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03135873.