Chapter Two - The Influence of Prebiotics on Neurobiology and Behavior

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Abstract

Manipulating the intestinal microbiota for the benefit of the brain is a concept that has become widely acknowledged. Prebiotics are nondigestible nutrients (i.e., fibers, carbohydrates, or various saccharides) that proliferate intrinsic, beneficial gut bacteria, and so provide an alternative strategy for effectively altering the enteric ecosystem, and thence brain function. Rodent studies demonstrating neurobiological changes following prebiotic intake are slowly emerging, and have thus far revealed significant benefits in disease models, including antiinflammatory and neuroprotective actions. There are also compelling data showing the robust and favorable effects of prebiotics on several behavioral paradigms including, anxiety, learning, and memory. At present, studies in humans are limited, though there is strong evidence for prebiotics modulating emotional processes and the neuroendocrine stress response that may underlie the pathophysiology of anxiety. While the mechanistic details linking the enteric microbiota to the central nervous system remain to be elucidated, there are a number of considerations that can guide future studies. These include the modulation of intestinal endocrine systems and inflammatory cascades, as well as direct interaction with the enteric nervous system and gut mucosa. Our knowledge of gut microbiome–brain communication is steadily progressing, and thorough investigations validating the use of prebiotics in the treatment of neuropsychiatric disorders would be highly valued and are encouraged.

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

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