Chapter Two - The Influence of Prebiotics on Neurobiology and Behavior
Introduction
Compelling evidence for the role of the gut microbiota as a potential therapeutic target for a broad range of neuropsychological disorders has been accumulating over the past decade. Preclinical and clinical studies have suggested that altered composition of enteric microbial communities is fundamental to the modulation of the microbiome–gut–brain axis. For example, in a behavioral investigation with mice, greater bacterial diversity in the colon was associated with improved working and reference memory when fed with standard rodent chow containing 50% lean ground beef (Li, Dowd, Scurlock, Acosta-Martinez, & Lyte, 2009). Similarly, oral administration of antibiotics has been shown to reverse overt hepatic encephalopathy, possibly through acidification of the gastrointestinal tract (Schiano, 2010).
In addition to diet and antibiotics, there are several additional approaches to manipulate the intestinal microbiome including exposure to activated carbon (Khoder, Tsapis, Domergue-Dupont, Gueutin, & Fattal, 2010), fecal microbiota transplantation (Collins, Kassam, & Bercik, 2013), or ingestion of natural dietary compounds. This latter group, which exhibits a high safety profile and is therefore preferred, consists of such as probiotics, prebiotics, polyphenols, amino acids, and dietary fibers. In efforts to manipulate the gut microbiota for the benefit of the brain, the effect of consuming specific microbial strains as live cultures (i.e., probiotics) on the psychological state of healthy volunteers have been explored. Reinforcing bacterial populations such as lactobacillus and bifidobacterium resulted in significantly improved psychological well-being in healthy volunteers after 30-days of ingestion (Messaoudi et al., 2011) as well as in patients with chronic fatigue syndrome after 60-days of ingestion (Rao et al., 2009).
The composition of the gut microbiota can also be altered by prebiotic consumption. These are nondigestible compounds, comprising primarily of carbohydrates or short chains of saccharide molecules. These molecules are naturally found within the mammalian diet and are also commercially available as dietary supplements in their purified form. Prebiotics enhance the simultaneous proliferation of specific indigenous microbiota by providing them with a source of energy. It is conceivable, therefore, that the ingestion of prebiotics might impart greater health benefits than probiotics; they have the potential to augment the growth of many beneficial microbial species, which would ultimately lead to greater bacterial diversity in the gut.
Section snippets
Prebiotics
Over the past decade, the definition of prebiotics has developed and matured into a very specific set of requirements. When the concept was first proposed over 20 years ago, prebiotics were described as any “nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria already resident in the colon” (Gibson & Roberfroid, 1995). In hindsight this definition is narrow and dismisses two major
Neurobiological Changes Associated with Prebiotic Intake
Prebiotic administration in preclinical models has shown significant peripheral and central changes. These results include altered expression of proteins associated with neuroprotection including antiinflammatory or antioxidant systems. Collectively, convincing data are available to support the use of prebiotics as a therapeutic agent in neurodegenerative disorders, although the robustness and replicability of these studies remain to be demonstrated. Prebiotics may also play a role in
Prebiotic-Mediated Changes in Behavior
While 3–4 weeks of probiotic-based manipulations of the intestinal microbial population have been shown to significantly elevate mood (Benton, Williams, & Brown, 2007), or alleviate psychological distress (Messaoudi et al., 2011) in healthy volunteers, research on the behavioral effects of prebiotics remains limited (Table 1, Table 2). In one study, 5.5 g/day of either B-GOS, FOS, or a placebo was ingested for 3 weeks by healthy volunteers, and the psychological mechanisms that underlie anxiety,
Mechanistic Considerations
Both direct and indirect mechanisms have been proposed to mediate the central effects of the gut microbiome. However, for oligosaccharide prebiotics, the significant production of SCFAs that results from their fermentation, may be the predominant mediator that relays changes in the enteric environment to the brain, either directly or via the gut endocrine and immune systems. In the case of gut hormones, SCFA production may elevate levels of circulating satiety peptides which are able to
Conclusion
Specific prebiotics, through their proliferative action on indigenous beneficial gut bacteria, influence host neurobiology and behavior. Numerous well-designed preclinical studies that demonstrate the downstream central molecular effects of prebiotics are slowly accumulating. Changes in the expression of brain receptors and/or the levels of circulating hormones and immune molecules may be crucial for attaining healthy microbiome–gut–brain communication. Based on current prebiotic studies, it
References (98)
- et al.
GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality
Psychoneuroendocrinology
(2016) - et al.
Selected indigestible oligosaccharides affect large bowel mass, cecal and fecal short-chain fatty acids, pH and microflora in rats
The Journal of Nutrition
(1997) - et al.
The adoptive transfer of behavioral phenotype via the intestinal microbiota: Experimental evidence and clinical implications
Current Opinion in Microbiology
(2013) - et al.
The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon
Cell Metabolism
(2011) - et al.
Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics
The Journal of Nutrition
(1995) - et al.
Chitosan oligosaccharides alleviate cognitive deficits in an amyloid-beta1-42-induced rat model of Alzheimer's disease
International Journal of Biological Macromolecules
(2016) - et al.
Inflammation and immunity in schizophrenia: Implications for pathophysiology and treatment
Lancet Psychiatry
(2015) - et al.
Removal of residual colonic ciprofloxacin in the rat by activated charcoal entrapped within zinc-pectinate beads
European Journal of Pharmaceutical Sciences
(2010) - et al.
Non-digestible long chain beta-glucans as novel prebiotics
Bioactive Carbohydrates and Dietary Fibre
(2013) - et al.
Memory and learning behavior in mice is temporally associated with diet-induced alterations in gut bacteria
Physiology & Behavior
(2009)
In vitro modulation of the human gastrointestinal microbial community by plant-derived polysaccharide-rich dietary supplements
International Journal of Food Microbiology
Possible antipsychotic effects of minocycline in patients with schizophrenia
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Inulin and oligofructose: What are they?
The Journal of Nutrition
Evaluation of marble-burying behavior as a model of anxiety
Pharmacology, Biochemistry, and Behavior
Lactobacillus and bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles
Gastroenterology
Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells
Gastroenterology
The bifidogenic nature of chicory inulin and its hydrolysis products
The Journal of Nutrition
Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine
Neurochemistry International
Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-beta levels in male mice
Brain, Behavior, and Immunity
Functional autoradiography of neuropeptide Y Y1 and Y2 receptor subtypes in rat brain using agonist stimulated [35S]GTPgammaS binding
Journal of Chemical Neuroanatomy
Galactooligosaccharide improves the animal survival and alleviates motor neuron death in SOD1G93A mouse model of amyotrophic lateral sclerosis
Neuroscience
PYY3-36: Beyond food intake
Frontiers in Neuroendocrinology
Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress
Neuroscience Letters
The prebiotics 3'Sialyllactose and 6'Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis
Brain, Behavior, and Immunity
The gut hormone glucagon-like peptide-1 produced in brain: Is this physiologically relevant?
Current Opinion in Pharmacology
Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents
The Journal of Nutritional Biochemistry
Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers
The American Journal of Clinical Nutrition
Agmatine prevents LPS-induced spatial memory impairment and hippocampal apoptosis
European Journal of Pharmacology
Host microbiota modulates development of social preference in mice
Microbial Ecology in Health and Disease
Impact of consuming a milk drink containing a probiotic on mood and cognition
European Journal of Clinical Nutrition
The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication
Neurogastroenterology and Motility
Prebiotics and bioactive milk fractions affect gut development, microbiota and neurotransmitter expression in piglets
Journal of Pediatric Gastroenterology and Nutrition
Saccharide effects on cognition and well-being in middle-aged adults: A randomized controlled trial
Developmental Neuropsychology
Inhibition of monocyte, lymphocyte, and neutrophil adhesion to endothelial cells by human milk oligosaccharides
Thrombosis and Haemostasis
Lactulose ingestion increases faecal bifidobacterial counts: A randomised double-blind study in healthy humans
European Journal of Clinical Nutrition
Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve
Proceedings of the National Academy of Sciences of the United States of America
Commensal bacteria at the interface of host metabolism and the immune system
Nature Immunology
Innate immune recognition of the microbiota promotes host-microbial symbiosis
Nature Immunology
The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner
Molecular Psychiatry
Short chain fatty acids in human large intestine, portal, hepatic and venous blood
Gut
Antipsychotics and the gut microbiome: Olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat
Translational Psychiatry
Digging and marble burying in mice: Simple methods for in vivo identification of biological impacts
Nature Protocols
Microbiota is essential for social development in the mouse
Molecular Psychiatry
Normal gut microbiota modulates brain development and behavior
Proceedings of the National Academy of Sciences of the United States of America
Prebiotic oligosaccharides: In vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties
Pediatric Allergy and Immunology
Host microbiota constantly control maturation and function of microglia in the CNS
Nature Neuroscience
On the role of glutamate in presynaptic development: Possible contributions of presynaptic NMDA receptors
Biomolecules
Bacterial infection causes stress-induced memory dysfunction in mice
Gut
Dietary prebiotics: Current status and new definition
Food Science and Technology Bulletin: Functional Foods
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2020, European NeuropsychopharmacologyCitation Excerpt :Their advantage over probiotics is that, rather than favoring the growth of only one species of microorganism, prebiotics lead to the proliferation of several beneficial bacteria (Gibson et al., 2004). Moreover, prebiotics play essential roles in the body and among them, benefits have been reported in the bone structure (Weaver et al., 2011), improvement in lipid metabolism (Vulevic et al., 2013), gut dysbiosis (Ducatelle et al., 2015), and in brain function (Kao et al., 2016). Several studies have suggested that prebiotics can improve dysbiosis and its inflammatory-associated state.
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2020, Neurobiology of DiseaseCitation Excerpt :Prebiotics affect a variety of metabolic pathways, often through their metabolic byproduct, short-chain fatty acids (SCFA; Louis et al., 2016). Recent studies have connected prebiotics to alterations in neurobiology affecting behavior (Kao et al., 2016), as well as specific links to the reduction of depression- and anxiety-like defensive behavioral responses in rodents (Burokas et al., 2017). While antibiotics, probiotics, and prebiotics have become rather canonical in the microbiome literature, newer terms appear with increasing frequency.
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