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Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiology of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiology, or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing? In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data analysis in IBS. Supported by the Spanish Ministry of Science and Innovation (MICINN, Spain), No. AGL2017-88801-P (to Sanz Y); the Miguel Server grant from the Spanish "Carlos III" Health Institute (ISCIII), No. CP19/00132 (to Benitez-Paez A); The Norwegian Research Council (Funding Post-doc Position for Bharath Halandur Nagaraja), No. FRIMEDBIO276010; and Helse Vest’s Research Funding, No. HV912243; and ERC H2020-MSCA-IF-2019, No. 895219 (to Haleem N).

Introduction: Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal (GI) symptoms, recently described as a disturbance of the brain-gut-microbiota (BGM) axis. To gain a better understanding of the mechanisms underlying the poorly understood etiology of IBS, we have designed a multifaceted study that aim to stratify the complex interaction and dysfunction between the brain, the gut, and the microbiota in patients with IBS. Methods: Deep phenotyping data from patients with IBS (n = 100) and healthy age- (between 18 and 65) and gender-matched controls (n = 40) will be collected between May 2019 and December 2021. Psychometric tests, questionnaires, human biological tissue/samples (blood, faeces, saliva, and GI biopsies from antrum, duodenum, and sigmoid colon), assessment of gastric accommodation and emptying using transabdominal ultrasound, vagal activity, and functional and structural magnetic resonance imaging (MRI) of the brain, are included in the investigation of each participant. A subgroup of 60 patients with IBS-D will be further included in a 12-week low FODMAP dietary intervention-study to determine short and long-term effects of diet on GI symptoms, microbiota composition and functions, molecular GI signatures, cognitive, emotional and social functions, and structural and functional brain signatures. Deep machine learning, prediction tools, and big data analyses will be used for multivariate analyses allowing disease stratification and diagnostic biomarker detection. Discussion: To our knowledge, this is the first study to employ unsupervised machine learning techniques and incorporate systems-based interactions between the central and the peripheral components of the brain-gut-microbiota axis at the levels of the multiomics, microbiota profiles, and brain connectome of a cohort of 100 patients with IBS and matched controls; study long-term safety and efficacy of the low-FODMAP diet on changes in nutritional status, gut microbiota composition, and metabolites; and to investigate changes in the brain and gut connectome after 12 weeks strict low-FODMAP-diet in patients with IBS. However, there are also limitations to the study. As a restrictive diet, the low-FODMAP diet carries risks of nutritional inadequacy and may foster disordered eating patterns. Strict FODMAP restriction induces a potentially unfavourable gut microbiota, although the health effects are unknown.

Trabajo presentado al 12th Federation of European Neuroscience Societies (FENS): Virtual Forum of NeuroScience, celebrado del 11 al 15 de julio de 2020., M.S.issupported by La Caixa Foundation INPhINT Fellowship (LCF/BQ/IN18/11660067), whichr eceived funding from EU-H2020 (MSCA-COFUNDNo.713673). Project received funding from Generalitat Valencia (PROMETEO/2019/015), Ministerio de Sanidad , Servicios Sociales e Igualdad (#2017I065) and Severo Ochoa Program for Centers of Excellence in R&D (SEV-2017-0723).

La presente invención se refiere a la cepa de Holdemanella biformis la cepa H. biformis CECT 9752 a sus componentes celulares, metabolitos, y moléculas secretadas, y a composiciones que comprenden los productos anteriores, así como al uso de dicha cepa, pero también del género Holdemanella, y a la especie H. biformis para la prevención de alteraciones de la homeostasis energética y del metabolismo de la glucosa, incluyendo entre otras la intolerancia a glucosa, la resistencia a la insulina, el síndrome metabólico y la diabetes. [ES], The present invention relates to the strain Holdemanella biformis, the strain H. biformis CECT 9752, its cellular components, metabolites and secreted molecules, and to compositions comprising the aforementioned products, in addition to the use of said strain, but also of the genus Holdemanella, and to the species H. biformis for preventing alterations in energy homeostasis and glucose metabolism, including, inter alia, glucose intolerance, insulin resistance, metabolic syndrome and diabetes. [EN], Consejo Superior de Investigaciones Científicas (España), A1 Solicitud de patente con informe sobre el estado de la técnica

La presente invención se refiere a la cepa Bifidobacterium longum subsp. infantis CECT 9720, a sus componentes celulares, metabolitos, y moléculas secretadas, y a composiciones que comprenden los productos anteriores, así como al uso de dicha cepa para la prevención y/o tratamiento de enfermedades inflamatorias intestinales e inflamación de hígado, así como patologías derivadas, como por ejemplo la cirrosis de hígado. [ES], The present invention relates to the strain Bifidobacterium longum subsp. infantis CECT 9720, to its cellular components, metabolites and secreted molecules, and to compositions comprising said products, as well as to the use of the strain to prevent and/or treat inflammatory bowel disease and liver inflammation, as well as associated diseases, such as liver cirrhosis. [EN], Consejo Superior de Investigaciones Científicas (España), Fundación de la Comunitat Valenciana para la Gestión de Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernández de Elche, Consorcio Centro de Investigación Biomédica en Red (CIBER), A1 Solicitud de patente con informe sobre el estado de la técnica

The present invention relates to the strain Phascolarctobacterium faecium DSM 32890 and to its use for the regulation of appetite and the treatment and/or prevention of overweight or the associated metabolic and immunological changes, specifically, hyperglycaemia, glucose intolerance, insulin resistance, dyslipidemia (hypertriglyceridemia, hypercholesterolemia), metabolic syndrome, diabetes and intestinal and/or peripheral tissue inflammation. [EN], La presente invención se refiere a la cepa P. faecium DSM 32890 y a su uso para regular el apetito y el tratamiento y/o la prevención del sobrepeso u las alteraciones metabólicas e inmunológicas asociadas: en concreto la hiperglucemia, la intolerancia a la glucosa, la resistencia insulínica, la dislipemía (hipertrigliceridemía, hipercolesterolemia), el síndrome metabólico, la diabetes y la inflamación intestinal y/o de tejidos periféricos. [ES], Consejo Superior de Investigaciones Científicas (España), A1 Solicitud de patente con informe sobre el estado de la técnica

The present invention relates to the strain Phascolarctobacterium faecium DSM 32890 and to its use for the regulation of appetite and the treatment and/or prevention of overweight or the associated metabolic and immunological changes, specifically, hyperglycaemia, glucose intolerance, insulin resistance, dyslipidemia (hypertriglyceridemia, hypercholesterolemia), metabolic syndrome, diabetes and intestinal and/or peripheral tissue inflammation. [EN] La presente invención se refiere a la cepa P. faecium DSM 32890 y a su uso para regular el apetito y el tratamiento y/o la prevención del sobrepeso u las alteraciones metabólicas e inmunológicas asociadas: en concreto la hiperglucemia, la intolerancia a la glucosa, la resistencia insulínica, la dislipemía (hipertrigliceridemía, hipercolesterolemia), el síndrome metabólico, la diabetes y la inflamación intestinal y/o de tejidos periféricos. [ES] Peer reviewed Consejo Superior de Investigaciones Científicas (España) A1 Solicitud de patente con informe sobre el estado de la técnica

Bacteria de Holdemanella sp. y uso de la misma. La presente invención se refiere a la cepa de Holdemanella biformis la cepa H. biformis CECT 9752 a sus componentes celulares, metabolitos, y moléculas secretadas, y a composiciones que comprenden los productos anteriores, así como al uso de dicha cepa, pero también del género Holdemanella, y a la especie H. biformis para la prevención de alteraciones de la homeostasis energética y del metabolismo de la glucosa, incluyendo entre otras la intolerancia a glucosa, la resistencia a la insulina, el síndrome metabólico y la diabetes., Consejo Superior de Investigaciones Científicas (España), A1 Solicitud de patente con informe sobre el estado de la técnica

Cepa de Bifidobacterium longum sub. infantis y uso de la misma. La presente invención se refiere a la cepa Bifidobacterium longum sub. infantis CECT 9720, a sus componentes celulares, metabolitos, y moléculas secretadas, y a composiciones que comprenden los productos anteriores, así como al uso de dicha cepa para la prevención y/o tratamiento de enfermedades inflamatorias intestinales e inflamación de hígado, así como patologías derivadas, como por ejemplo la cirrosis de higado., Consejo Superior de Investigaciones Científicas (España), Universidad Miguel Hernández de Elche, Consorcio Centro de Investigación Biomédica en Red (CIBER), Fundación de la C.V. para la gestión de Instituto de Investigación Sanitaria y Biomédica de Alicante., A1 Solicitud de patente con informe sobre el estado de la técnica