Influence of gut microbiota on neuropsychiatric disorders

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson’s disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and the possible microbiota-targeted intervention strategies that could improve health status and prevent psychiatric disorders in the near future.Peer reviewe

Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects

7 pages, 1 figure, 3 tables.Diet influences the composition of the gut microbiota and host's health, particularly in patients suffering from food-related diseases. Coeliac disease (CD) is a permanent intolerance to cereal gluten proteins and the only therapy for the patients is to adhere to a life-long gluten-free diet (GFD). In the present preliminary study, the effects of a GFD on the composition and immune function of the gut microbiota were analysed in ten healthy subjects (mean age 30·3 years) over 1 month. Faecal microbiota was analysed by fluorescence in situ hybridisation (FISH) and quantitative PCR (qPCR). The ability of faecal bacteria to stimulate cytokine production by peripheral blood mononuclear cells (PBMC) was determined by ELISA. No significant differences in dietary intake were found before and after the GFD except for reductions (P = 0·001) in polysaccharides. Bifidobacterium, Clostridium lituseburense and Faecalibacterium prausnitzii proportions decreased (P = 0·007, P = 0·031 and P = 0·009, respectively) as a result of the GFD analysed by FISH. Bifidobacterium, Lactobacillus and Bifidobacterium longum counts decreased (P = 0·020, P = 0·001 and P = 0·017, respectively), while Enterobacteriaceae and Escherichia coli counts increased (P = 0·005 and P = 0·003) after the GFD assessed by qPCR. TNF-α, interferon-γ, IL-10 and IL-8 production by PBMC stimulated with faecal samples was also reduced (P = 0·021, P = 0·037, P = 0·002 and P = 0·007, respectively) after the diet. Therefore, the GFD led to reductions in beneficial gut bacteria populations and the ability of faecal samples to stimulate the host's immunity. Thus, the GFD may constitute an environmental variable to be considered in treated CD patients for its possible effects on gut health.This work was supported by grants AGL2008-01440/ALI and Consolider Fun-C-Food 20 CSD2007-00063 from the Spanish Ministry of Science and Innovation.Peer reviewe

Microorganismos para mejorar el estado de salud de individuos con trastornos relacionados con la ingesta de gluten

La presente invención aporta microorganismos para el tratamientode alergias alimentarias, más concretamente la enfermedad celiaca, así como métodos para su sección. Sus mecanismos de acción incluyen: (i) la regulación de la respuesta inmunológica innata y adaptativa; (ii) la reducción de la concentración de epítopos tóxicos en la luz intestinal; (iii) el fortalecimiento de la función barrera defensiva frente a bacterias y antígenos perjudiciales, y (iv) el aporte de actividades enzimáticas que favorecen la digestión.Peer reviewedConsejo Superior de Investigaciones Científicas (España)T3 Traducción de patente europe

Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin

Background: Human gut bacteria can synthesize proteinogenic amino acids and produce a range of metabolites via protein fermentation, some known to exert beneficial or harmful physiological effects on the host. However, the effects of the type and amount of dietary protein consumed on these metabolic processes, as well as the effects of the microbiota-derived amino acids and related metabolites on the host health are still predominantly unknown. Scope and approach:This review provides an up-to-date description of the dominant pathways/genes involved in amino acid metabolism in gut bacteria, and provides an inventory of metabolic intermediates derived from bacterial protein fermentation that may affect human health. Advances in understanding bacterial protein fermentation pathways and metabolites generated at a global level via the implementation of ‘omics’ technologies are reviewed. Finally, the impact of dietary protein intake and high-protein diets on human health is discussed. Key findings and conclusions:The intestinal microbiota is able to synthesize amino acids, but the net result of amino acid production and utilization, according to dietary patterns still needs to be determined. The amount of ingested dietary protein appears to modify both the diversity and composition of the intestinal microbiota as well as the luminal environment of the intestinal epithelium and peripheral tissues. The understanding of the consequences of such changes on the host physiology and pathophysiology is still in an early stage but major progress is expected in the near future with the investigation of host-microbe omics profiles from well-controlled human intervention studies.This works is supported by the European Union's Seventh Framework Program under the grant agreement no 613979 (MyNewGut).Peer reviewe

Gut microbiota, diet, and obesity-related disorders - The good, the bad, and the future challenges

Diet has been shown to be a major factor in modulating the structure of the mammalian gut microbiota by providing specific nutrient sources and inducing environmental changes (pH, bile acids) in the gut ecosystem. Long-term dietary patterns and short-term interventions have been shown to induce changes in gut microbiota structure and function, with several studies revealing metabolic changes likely resulting from the host microbiota cross-talk, which ultimately could influence host physiology. However, a more precise identification of the specific dietary patterns and food constituents that effectively modulate the gut microbiota and bring a predictable benefit to the host metabolic phenotype is needed to establish microbiome-based dietary recommendations. Here, we briefly review the existing data regarding gut microbiota changes induced by different macronutrients and the resulting metabolites produced via their respective fermentation, including their potential effects on obesity and associated metabolic disorders. We also discuss major limitations of current dietary intervention studies as well as future needs of applying cutting-edge “omic” techniques and of progressing in functional microbiota gene discovery to establish robust causal relationships between the dietary microbiota induced changes and metabolic health or disease.This works is supported by the European Union’s Seventh Framework Program under the grant agreement no 613979 (MyNewGut) and grant AGL2014-52101-P from the Spanish Ministry of Economy and Competitiveness (MINECO, Spain). The FPU scholarship of V. Cerrudo from MECD (Spain) is fully acknowledged.Peer reviewe

The Allium Derivate Propyl Propane Thiosulfinate Exerts Anti-Obesogenic Effects in a Murine Model of Diet-Induced Obesity

This study is supported by the Spanish Ministry of Science and Innovation (MICINN) (grants PID2020-119536RB-I00 and CIEN IDI-20170847). The FPU contract to R.L.-G. from Spanish Ministry of Universities (FPU 18/02026) and the contract Juan de la Cierva-Incorporacion (IJCI-2017-32485) to MO are fully acknowledge.Allium species and their organosulfur-derived compounds could prevent obesity and metabolic dysfunction, as they exhibit immunomodulatory and antimicrobial properties. Here, we report the anti-obesogenic potential and dose-dependent effects (0.1 or 1 mg/kg/day) of propyl propane thiosulfinate (PTS) in a murine model of diet-induced obesity. The obesogenic diet increased body weight gain and adipocyte size, and boosted inflammatory marker (Cd11c) expression in the adipose tissue. Conversely, PTS prevented these effects in a dose-dependent manner. Moreover, the higher dose of PTS improved glucose and hepatic homeostasis, modulated lipid metabolism, and raised markers of the thermogenic capacity of brown adipose tissue. In the colon, the obesogenic diet reduced IL-22 levels and increased gut barrier function markers (Cldn3, Muc2, Reg3g, DefaA); however, the highest PTS dose normalized all of these markers to the levels of mice fed a standard diet. Gut microbiota analyses revealed no differences in diversity indexes and only minor taxonomic changes, such as an increase in butyrate producers, Intestimonas and Alistipes, and a decrease in Bifidobacterium in mice receiving the highest PTS dose. In summary, our study provides preclinical evidence for the protective effects of PTS against obesity, which if confirmed in humans, might provide a novel plant-based dietary product to counteract this condition.Spanish GovernmentEuropean Commission PID2020-119536RB-I00 CIEN IDI-20170847Spanish Government FPU 18/02026contract Juan de la Cierva-Incorporacion IJCI-2017-3248

Microbiome-based solutions to address new and existing threats to food security, nutrition, health and agrifood systems' sustainability

In addition to challenges like climate change and biodiversity loss, the sustainability and resilience of agrifood systems worldwide are currently challenged by new threats, such as the COVID-19 pandemic and the Ukraine war. Furthermore, the resilience and sustainability of our agrifood systems need to be enhanced in ways that simultaneously increase agricultural production, decrease post-harvest food losses and food waste, protect the climate, environment and health, and preserve biodiversity. The precarious situation of agrifood systems is also illustrated by the fact that overall, around 3 billion people worldwide still do not have regular access to a healthy diet. This results in various forms of malnutrition, as well as increasing number of people suffering from overweight and obesity, and diet-related, non-communicable diseases (NCDs) around the world. Findings from microbiome research have shown that the human gut microbiome plays a key role in nutrition and diet-related diseases and thus human health. Furthermore, the microbiome of soils, plants, and animals play an equally important role in environmental health and agricultural production. Upcoming, microbiome-based solutions hold great potential for more resilient, sustainable, and productive agrifood systems and open avenues toward preventive health management. Microbiome-based solutions will also be key to make better use of natural resources and increase the resilience of agrifood systems to future emerging and already-known crises. To realize the promises of microbiome science and innovation, there is a need to invest in enhancing the role of microbiomes in agrifood systems in a holistic One Health approach and to accelerate knowledge translation and implementation.YS, KD'H, LL, HS, LO, TK, EM, AM, IS, and AS received funding from the European Union's H2020 Research and Innovation Programme under Grant No. 818116 (Microbiome Support).Peer reviewe

Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome

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).Peer reviewe

Body-brain-microbiome interaction

Brain function is influenced by internal inputs from many parts of the body, including chemicals in the blood and bacteria in the gut. The gut microbiota is a fundamental component of the body that can be transferred across generations and contribute to the unique features of the human phenotype influencing both health and disease. Deciphering the controlling mechanisms of microbiome-bodybrain interactions may help in identifying new molecular targets to prevent and/or treat a range of psychiatric and neurologic disorders as well as their physical comorbidities. Here we provide an update on the functioning of the gut microbiome-body-brain axis and outline open scientific challenges and future research directions.Peer reviewe

Libro Blanco Volumen 5: Cerebro, mente y comportamiento

Llegar a entender cómo funciona el cerebro y cómo este interacciona con el ecosistema para interpretar el mundo que nos rodea sin duda facilitará el desarrollo de estrategias más eficaces para tratar o curar los trastornos neurológicos y psiquiátricos. Además, la comprensión de los principios fundamentales que controlan el funcionamiento del sistema nervioso transformará nuestra visión sobre muchas cuestiones que han sido tradicionalmente enmarcadas en el campo de la filosofía, repercutiendo en áreas como la economía o el derecho. Las neurociencias nos ayudarán, en definitiva, a entender qué nos hace humanos. Este es un campo en el que los investigadores del CSIC destacan internacionalmente y así debe seguir siendo en los próximos años. Para lograrlo, deberíamos potenciar y reforzar nuestras investigaciones en los ocho desafíos que describimos en este volumen.Peer reviewe