!!José Manuel Fernández-Real - Selected Publications
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Google scholar H-index 99 (40,161 citations, i10-index 420)\\
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1. Wu H, Esteve E, Tremaroli V, Caesar R,…, Fernàndez-Real JM, Bäckhed F. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nature Medicine. 2017;23(7):850-858. PMID: 28530702, doi:10.1038/nm.4345. Corresponding (AC): yes. IF (2022): 82.9; Rank: 1/285 (Biochemistry & Molecular Biology, D1). (Citations: 1292). Statement: We investigated metformin–microbiota interactions, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects. I conceived, designed the study, recruited cohort individuals, performed the clinical study, and contributed to write the manuscript.\\
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2. Hoyles L, Fernández-Real JM, Federici M, et al. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nature Medicine. 2018;24 (7):1070-1080. PMID: 30093731, doi: 10.1038/s41591-018-0169-5. Corresponding (AC): yes. IF (2022): 82.9; Rank: 1/285 (Biochemistry & Molecular Biology, D1). (Citations: 481). Statement: We combine shotgun sequencing of faecal metagenomes with molecular phenomics (hepatic transcriptome, plasma and urine metabolomes) in two well-characterized cohorts of morbidly obese women recruited to the FLORINASH study. We reveal molecular networks linking gut microbiome and host phenome to hepatic steatosis. I designed the study, supervised all parts of the project, implemented the microarray data analysis workflow, designed the clinical protocol, oversaw the clinical activities, and contributed to write the manuscript. \\
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3. Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Burokas A, , Fernández-Real JM. Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids. Cell Metabolism. 2020;32(4):548-560.e7. PMID: 33027674, doi: 10.1016/j.cmet.2020.09.002. Corresponding (AC): yes. IF (2022): 29.0; Rank: 8/191 (Cell Biology, D1). (Citations: 88). Statement: We revealed an obesity-modulated microbiota profile linked to brain regions and memory through aromatic amino acid and one-carbon metabolism. We registered a patent (patent registered # 3) that proposed the high value of the microbiota for memory improvement. I carried out the conception and coordination of the study, researched the data, and wrote the manuscript.\\
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4. Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, …, Fernàndez-Real JM. Microbiota alterations in proline metabolism impact depression. Cell Metabolism. 2022;34(5):681-701.e10. PMID: 35508109, doi: 10.1016/j.cmet.2022.04.001. Corresponding (AC): yes. IF (2022): 29.0; Rank: 8/191 (Cell Biology, D1). (Citations: 58). Statement: We used a multi-omics approach to pioneer the identification of microbial-dependent elevations in plasma proline linked to severity depression in humans. Fecal transplantation induced an emotional impaired phenotype in mice. Knockdown of proline transport protected flies against depression. This opens novel windows for depression treatment. I carried out the design and conception and coordination of the study, researched the data, and wrote the manuscript.\\
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5. Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, …, Fernàndez-Real JM. Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans. Cell Host Microbe. 2022;30(3):340-356.e8. PMID: 35176247, doi: 10.1016/j.chom.2022.01.013. Corresponding (AC): yes. IF (2022): 30.3; Rank: 4/135 (Microbiology, D1). (Citations: 49).  Statement: We uncovered a role for bacteriophages in microbiome structure and metabolism with downstream effects on neuronal expression of memory-related genes and cognition. This highlighted the potential of phage therapy to improve memory (patent registered # 5). Awarded best biomedical publication in Spain (2022) by Fundación Atresmedia (“Constantes y Vitales Awards”). I carried out the design and conception and coordination of the study, researched the data, and wrote the manuscript.\\
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6. García-Blanco A, ... Fernández-Real JM, ... miRNA signatures associated with vulnerability to food addiction in mice and humans. Journal of Clinical Investigation. 2022;132(10): e156281. PMID: 35349487, doi: 10.1172/JCI156281. Corresponding (AC): yes. IF (2022): 15.9; Rank: 3/136 (Medicine, Research & Experimental, D1). (Citations: 7). Statement: We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression. I conceived, designed the experimental approaches used in the human cohort, and contributed to write the manuscript.\\
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7. Mayneris-Perxachs J, Moreno-Navarrete JM, Fernández-Real JM. The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism. Nature Reviews Endocrinology. 2022;18(11):683-698.  PMID: 35986176, doi: 10.1038/s41574-022-00721-3. Corresponding (AC): yes. IF (2022): 40.5; Rank: 2/145 (Endocrinology & Metabolism, D1). (Citations: 24). Statement: Due to the impact of our research identifying the impact of the gut microbiota on cardiometabolic disease (obesity, NAFLD), we were invited to write a review for Nature Reviews Endocrinology. We postulated that the regulation of systemic homeostasis (both glucose and iron metabolism) needs to consider the role of the microbiota and its bidirectional interactions with the host and that an in-depth analysis of this crosstalk using personalized and specific disease-oriented approaches will have therapeutic implications for chronic low-grade inflammation that occurs in metabolic disease. I have been extended an invitation to review this subject matter by the Journal, carried out the conception and coordination of the manuscript, wrote and postulated the impact of the gut microbiota on iron and glucose metabolism.\\
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8. Fernández-Real JM, Manco M. Effects of iron overload on chronic metabolic diseases. Lancet Diabetes Endocrinology. 2014;2(6):513-26. PMID: 24731656, doi: 10.1016/S2213-8587(13)70174-8. Corresponding (AC): yes. IF (2022): 44.5; Rank: 1/145 (Endocrinology & Metabolism, D1). (Citations: 224). Statement: We were pioneers in the field of iron metabolism and its connection to metabolism (PMID: 9580307 Diabetes Care 1998). This paper consolidates the theory published in this groundbreaking article. We discuss the effect of iron overload on major tissues involved in glucose and lipid metabolism (liver, adipose tissue, muscle, and pancreatic β cells) and organs that are affected by chronic diabetic complications (retina, kidney, brain, and vasculature;). I have been extended an invitation to review this subject matter by the Journal and prepared the manuscript.\\
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9. Perakakis N, Triantafyllou GA, Fernández-Real JM, Huh JY, Park KH, Seufert J, Mantzoros CS. Physiology and role of irisin in glucose homeostasis. Nature Reviews Endocrinology. 2017;13(6):324-337. PMID: 28211512, doi: 10.1038/nrendo.2016.221. Corresponding (AC): no. IF (2022): 40.5; Rank: 2/145 (Endocrinology & Metabolism, D1). (Citations: 520). Statement: We present the current knowledge on the physiology of irisin and its role in glucose homeostasis. We describe the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement of irisin. We also discuss the direct effects of irisin on glucose regulatory mechanisms in different organs, the indirect effects and interactions with other hormones, and the important open questions with regard to irisin in those organs. Finally, we present the results from animal interventional studies and from human clinical studies investigating the association of irisin with obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome. I contributed to discussion of the content, wrote parts of the article and reviewed and/or edited the article before submission.\\
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10. Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Contreras-Rodríguez O, …, Fernández-Real JM. Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways. Gut. 2021: gutjnl-2020-323371. PMID: 33514598, doi: 10.1136/gutjnl-2020-323371. Corresponding (AC): yes. IF (2022): 24.5; Rank: 5/93 (Gastroenterology & Hepatology D1). (Citations: 27). Statement: We unravelled a link of the gut microbiome composition and function with inhibitory control and brain regions related to this cognitive domain in obese subjects. The inhibitory control impairment was phenocopied to mice by fecal microbiota transplantation. This opens new strategies to tackle obesity. I carried out the design and conception and coordination of the study, researched the data, and wrote the manuscript.\\ \\[{ALLOW view All}][{ALLOW edit jfernandez-real}][{ALLOW upload jfernandez-real}][{ALLOW comment All}]