The Effect of a Diet Enriched with Jerusalem artichoke, Inulin, and Fluoxetine on Cognitive Functions, Neurogenesis, and the Composition of the Intestinal Microbiota in Mice

The aim of the study was to assess the effect of long-term administration of natural prebiotics: Jerusalem artichoke (topinambur, TPB) and inulin (INU) as well as one of the most popular antidepressants, fluoxetine (FLU), on the proliferation of neural stem cells, learning and memory functions, and the composition of the intestinal microbiota in mice. Cognitive functions were assessed using the Morris Water Maze (MWM)Test. Cells were counted using a confocal microscope and ImageJ software. We performed 16S rRNA sequencing to assess changes in the gut microbiome of the mice. The obtained results showed that the 10-week supplementation with TPB (250 mg/kg) and INU (66 mg/kg) stimulates the growth of probiotic bacteria, does not affect the learning and memory process, and does not disturb the proliferation of neural stem cells in the tested animals. Based on this data, we can assume that both TPB and INU seem to be safe for the proper course of neurogenesis. However, 2-week administration of FLU confirmed an inhibitory impact on Lactobacillus growth and negatively affected behavioral function and neurogenesis in healthy animals. The above studies suggest that the natural prebiotics TPB and INU, as natural supplements, may have the potential to enrich the diversity of intestinal microbiota, which may be beneficial for the BGM axis, cognitive functions, and neurogenesis.

[1]  Jian-jun Chen,et al.  Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder , 2022, Frontiers in Cellular and Infection Microbiology.

[2]  D. Middlemas,et al.  Chronic SSRI Treatment, but Not Norepinephrine Reuptake Inhibitor Treatment, Increases Neurogenesis in Juvenile Rats , 2022, International journal of molecular sciences.

[3]  Y. Rodríguez-Carmona,et al.  Use of Fluoxetine to Reduce Weight in Adults with Overweight or Obesity: Abridged Republication of the Cochrane Systematic Review , 2022, Obesity Facts.

[4]  L. Wold,et al.  Influence of the Microbiota-Gut-Brain Axis on Cognition in Alzheimer's Disease. , 2022, Journal of Alzheimer's disease : JAD.

[5]  Xia Li,et al.  Gut-Brain Axis: Possible Role of Gut Microbiota in Perioperative Neurocognitive Disorders , 2021, Frontiers in Aging Neuroscience.

[6]  Liwei Sun,et al.  Gut Microbiota and SCFAs Play Key Roles in QingFei Yin Recipe Anti-Streptococcal Pneumonia Effects , 2021, Frontiers in Cellular and Infection Microbiology.

[7]  M. Andres-Mach,et al.  Effect of Lacosamide and Ethosuximide Chronic Treatment on Neural Precursor Cells and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice , 2021, Brain sciences.

[8]  B. Kuhla,et al.  A high-protein diet containing inulin/oligofructose supports body weight gain associated with lower energy expenditure and carbohydrate oxidation, and alters faecal microbiota in C57BL/6 mice , 2021, Journal of Nutritional Science.

[9]  Jinying Xu,et al.  Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders , 2021, Nutrients.

[10]  S. Friess,et al.  Gut microbial dysbiosis after traumatic brain injury modulates the immune response and impairs neurogenesis , 2021, Acta neuropathologica communications.

[11]  M. Andres-Mach,et al.  Preclinical Assessment of a New Hybrid Compound C11 Efficacy on Neurogenesis and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice , 2021, International journal of molecular sciences.

[12]  He Yan,et al.  Antidepressants fluoxetine and amitriptyline induce alterations in intestinal microbiota and gut microbiome function in rats exposed to chronic unpredictable mild stress , 2021, Translational Psychiatry.

[13]  M. Saier,et al.  Gut Bacteroides species in health and disease , 2021, Gut microbes.

[14]  Haibo Yu,et al.  Fecal Microbiota Changes in Patients With Postpartum Depressive Disorder , 2020, Frontiers in Cellular and Infection Microbiology.

[15]  P. Rodrigues,et al.  Diet-dependent gut microbiota impacts on adult neurogenesis through mitochondrial stress modulation , 2020, Brain communications.

[16]  Gavin M Douglas,et al.  PICRUSt2 for prediction of metagenome functions , 2020, Nature Biotechnology.

[17]  J. Epp,et al.  Disrupted Neurogenesis in Germ-Free Mice: Effects of Age and Sex , 2020, Frontiers in Cell and Developmental Biology.

[18]  A. Kaczmarczyk-Ziemba,et al.  First Insight into Microbiome Profiles of Myrmecophilous Beetles and Their Host, Red Wood Ant Formica polyctena (Hymenoptera: Formicidae)—A Case Study , 2020, Insects.

[19]  A. Kurilshikov,et al.  Impact of commonly used drugs on the composition and metabolic function of the gut microbiota , 2020, Nature Communications.

[20]  Jianguo Xia,et al.  Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data , 2020, Nature Protocols.

[21]  R. Rola,et al.  Evaluation of the impact of compound C11 a new anticonvulsant candidate on cognitive functions and hippocampal neurogenesis in mouse brain , 2019, Neuropharmacology.

[22]  D. Philpott,et al.  Nod‐like receptors are critical for gut–brain axis signalling in mice , 2019, The Journal of physiology.

[23]  Hae Ung Lee,et al.  Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice , 2019, Science Translational Medicine.

[24]  G. Cui,et al.  Fluoxetine ameliorates dysbiosis in a depression model induced by chronic unpredicted mild stress in mice , 2019, International journal of medical sciences.

[25]  T. Dinan,et al.  Mood and Microbes: Gut to Brain Communication in Depression. , 2019, Gastroenterology clinics of North America.

[26]  William A. Walters,et al.  Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2 , 2019, Nature Biotechnology.

[27]  M. Andres-Mach,et al.  Topinambur - new possibilities for use in a supplementation diet. , 2019, Annals of agricultural and environmental medicine : AAEM.

[28]  Liang Zhong,et al.  Inulin Can Alleviate Metabolism Disorders in ob/ob Mice by Partially Restoring Leptin-related Pathways Mediated by Gut Microbiota , 2019, Genom. Proteom. Bioinform..

[29]  M. Lyte,et al.  Fluoxetine-induced alteration of murine gut microbial community structure: evidence for a microbial endocrinology-based mechanism of action responsible for fluoxetine-induced side effects , 2019, PeerJ.

[30]  E. Quigley Prebiotics and Probiotics in Digestive Health , 2019, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[31]  Gabriel Herrera-López,et al.  Probiotics and Prebiotics as a Therapeutic Strategy to Improve Memory in a Model of Middle-Aged Rats , 2018, Front. Aging Neurosci..

[32]  T. Dinan,et al.  Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function , 2018, Psychopharmacology.

[33]  Qingping Wu,et al.  Prebiotic Effect of Fructooligosaccharides from Morinda officinalis on Alzheimer’s Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis , 2017, Front. Aging Neurosci..

[34]  K. Śliżewska,et al.  Effects of Probiotics, Prebiotics, and Synbiotics on Human Health , 2017, Nutrients.

[35]  R. Roth,et al.  Cognitive performance of juvenile monkeys after chronic fluoxetine treatment , 2017, Developmental Cognitive Neuroscience.

[36]  Jasmine Chong,et al.  MicrobiomeAnalyst: a web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data , 2017, Nucleic Acids Res..

[37]  J. Łuszczki,et al.  A Long-Term Treatment with Arachidonyl-2′-Chloroethylamide Combined with Valproate Increases Neurogenesis in a Mouse Pilocarpine Model of Epilepsy , 2017, International journal of molecular sciences.

[38]  I. Thiele,et al.  Gut microbiota functions: metabolism of nutrients and other food components , 2017, European Journal of Nutrition.

[39]  Kenji Sonomoto,et al.  Impact of Westernized Diet on Gut Microbiota in Children on Leyte Island , 2017, Front. Microbiol..

[40]  L. Samal,et al.  Effects of dietary supplementation with Jerusalem artichoke ( Helianthus tuberosus L.) tubers on growth performance, nutrient digestibility as well as activity and composition of large intestinal microbiota in rats , 2017 .

[41]  T. Dinan,et al.  Gut–brain axis in 2016: Brain–gut–microbiota axis — mood, metabolism and behaviour , 2017, Nature Reviews Gastroenterology &Hepatology.

[42]  K. Rudi,et al.  Modulation of the gut microbiota by prebiotic fibres and bacteriocins , 2017, Microbial ecology in health and disease.

[43]  M. Bebianno,et al.  Uptake, accumulation and metabolization of the antidepressant fluoxetine by Mytilus galloprovincialis. , 2016, Environmental pollution.

[44]  Paul J. McMurdie,et al.  DADA2: High resolution sample inference from Illumina amplicon data , 2016, Nature Methods.

[45]  R. Milo,et al.  Revised Estimates for the Number of Human and Bacteria Cells in the Body , 2016, bioRxiv.

[46]  X. Wu,et al.  Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress , 2015, Neuroscience.

[47]  R. Rola,et al.  ACEA (a highly selective cannabinoid CB1 receptor agonist) stimulates hippocampal neurogenesis in mice treated with antiepileptic drugs , 2015, Brain Research.

[48]  J. Graf,et al.  Early Life Experience and Gut Microbiome: The Brain–Gut–Microbiota Signaling System , 2015, Advances in neonatal care : official journal of the National Association of Neonatal Nurses.

[49]  T. Dinan,et al.  Adult Hippocampal Neurogenesis Is Regulated by the Microbiome , 2015, Biological Psychiatry.

[50]  M. Fischbach,et al.  Small molecules from the human microbiota , 2015, Science.

[51]  J. Ahmed,et al.  Sertraline enhances the activity of antimicrobial agents against pathogens of clinical relevance , 2015, Journal of Biological Research-Thessaloniki.

[52]  H. Cameron,et al.  Adult neurogenesis: beyond learning and memory. , 2015, Annual review of psychology.

[53]  P. Cowen,et al.  Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers , 2014, Psychopharmacology.

[54]  T. Dinan,et al.  Conference on 'Diet, gut microbiology and human health' Symposium 4: Manipulating the microbiome: health and therapeutic opportunities: Gut microbiota, the pharmabiotics they produce and host health , 2014 .

[55]  L. Reneman,et al.  Effects of Chronic Fluoxetine Treatment on Neurogenesis and Tryptophan Hydroxylase Expression in Adolescent and Adult Rats , 2014, PloS one.

[56]  J. Cryan,et al.  Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis , 2014, Genes, brain, and behavior.

[57]  M. Gareau Microbiota-gut-brain axis and cognitive function. , 2014, Advances in experimental medicine and biology.

[58]  S. Collins,et al.  The effects of inflammation, infection and antibiotics on the microbiota-gut-brain axis. , 2014, Advances in experimental medicine and biology.

[59]  John F. Cryan,et al.  Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease , 2014, Advances in Experimental Medicine and Biology.

[60]  F. Guarner,et al.  The intestinal microbiome, probiotics and prebiotics in neurogastroenterology , 2013, Gut microbes.

[61]  Pelin Yilmaz,et al.  The SILVA ribosomal RNA gene database project: improved data processing and web-based tools , 2012, Nucleic Acids Res..

[62]  A. Klindworth,et al.  Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies , 2012, Nucleic acids research.

[63]  T. Dinan,et al.  Mind-altering Microorganisms: the Impact of the Gut Microbiota on Brain and Behaviour , 2022 .

[64]  B. Berger,et al.  The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut–brain communication , 2011, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[65]  John F. Cryan,et al.  Brain–Gut–Microbe Communication in Health and Disease , 2011, Front. Physio..

[66]  John F. Cryan,et al.  Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve , 2011, Proceedings of the National Academy of Sciences.

[67]  C. Huttenhower,et al.  Metagenomic biomarker discovery and explanation , 2011, Genome Biology.

[68]  J. Cryan,et al.  The microbiome‐gut‐brain axis: from bowel to behavior , 2011, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[69]  John F. Cryan,et al.  Maternal separation as a model of brain–gut axis dysfunction , 2011, Psychopharmacology.

[70]  I. Lucki,et al.  Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice , 2010, Neuroscience Letters.

[71]  E. Murphy,et al.  Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models , 2010, Gut.

[72]  S. Massart,et al.  Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa , 2010, Proceedings of the National Academy of Sciences.

[73]  B. Finlay,et al.  Gut microbiota in health and disease. , 2010, Physiological reviews.

[74]  S. Talbott,et al.  Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes. , 2009, Journal of sports science & medicine.

[75]  T. R. Licht,et al.  Some putative prebiotics increase the severity of Salmonella enterica serovar Typhimurium infection in mice , 2009, BMC Microbiology.

[76]  E. Mayer,et al.  Principles and clinical implications of the brain–gut–enteric microbiota axis , 2009, Nature Reviews Gastroenterology &Hepatology.

[77]  E. A. Zaky Physiological Response to Diets Fortified with Jerusalem Artichoke Tubers (Helianthus tuberosus L.) Powder by Diabetic Rats , 2009 .

[78]  D. S. Cowen,et al.  Age-dependent decline in hippocampal neurogenesis is not altered by chronic treatment with fluoxetine , 2008, Brain Research.

[79]  P. Hof,et al.  Antidepressant drug‐induced stimulation of mouse hippocampal neurogenesis is age‐dependent and altered by early life stress , 2008, The Journal of comparative neurology.

[80]  P. Kristjansen,et al.  Increase in neurogenesis and behavioural benefit after chronic fluoxetine treatment in Wistar rats , 2007, Acta neurologica Scandinavica.

[81]  Andrew P. Smith The concept of well-being: relevance to nutrition research , 2005, British Journal of Nutrition.

[82]  M. Messaoudi,et al.  Behavioural and cognitive effects of oligofructose-enriched inulin in rats , 2005, British Journal of Nutrition.

[83]  Y. Chida,et al.  Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice , 2004, The Journal of physiology.

[84]  N. Naghdi,et al.  Impaired spatial learning in the Morris water maze induced by serotonin reuptake inhibitors in rats , 2002, Behavioural pharmacology.

[85]  O Hammer-Muntz,et al.  PAST: paleontological statistics software package for education and data analysis version 2.09 , 2001 .

[86]  P. Andrews,et al.  Fundamentals of neurogastroenterology , 1999, Gut.

[87]  J. Ahuja,et al.  Presence of inulin and oligofructose in the diets of Americans. , 1999, The Journal of nutrition.

[88]  C. Bowden,et al.  Fluoxetine: A Serotonin‐specific, Second‐generation Antidepressant , 1987, Pharmacotherapy.