Mini reviewA dynamic partnership: Celebrating our gut flora
Introduction
Among body sites normally sporting a community of microbes, the human gut, predominately the colon, harbors the greatest number and diversity of organisms, primarily bacteria. Pasteur with prescient insight postulated that our health is intertwined with our resident flora [1]. Dr. Joshua Lederberg, a Nobel Laureate (1958) at the age of 33, later coined the term ‘microbiome’ or the collective genome of our indigenous microbes and further proposed that a comprehensive view of human genetics and physiology is a composite of human and microbial genetics [2]. Later, the human genome project revealed 233 proteins with homologues only in bacteria, suggesting that we have acquired these genes from our resident flora [3]. This has led to a fundamental question; namely, to what extent is human life dependent on its microflora? [4] Investigations addressing this question have spawned two new scientific disciplines. The first titled ‘Eco-Devo’ or ecological developmental biology pursues the hypothesis that human development is both hardwired in our genes and derived from our interactions with microbes [5]. The second field, cellular microbiology, is built on the principle that studies of normal flora as well as microbial pathogens provide new insights into host cell biology, biochemistry and development [6]. The goal of this paper is to provide a perspective on recent data supporting the hypothesis that the relationship between the host and the gut flora is not simply commensal (i.e. living together without injury to either partner) but rather symbiotic or mutualistic; namely, an interdependent relationship essential to our well-being (Table 1) [2], [7].
Section snippets
Basic facts about the human gut flora
Comprised of 500 to 1000 bacterial species with two to four million genes, the microbiome contains about 100-fold more genes than the human genome and the estimated 1013 bacterial cells in the gut exceeds by 10-fold the total ensemble of human cells [2]. At least half of these organisms cannot be cultured but no one discounts the importance of these elusive microbes. In this vast community of gut bacteria, anaerobes outnumber aerobes by estimates of 100–1000 anaerobes to one aerobe. The
Nutritional benefits of the gut flora
In 1983, Wostmann and colleagues observed that germ-free rodents require 30% more calories to maintain their body mass than conventional rodents (possessing their ‘normal’ gut flora) [15]. The potential mechanisms accounting for this observation remained obtuse until recently when seminal studies by Drs. Lora Hooper, Jeffrey Gordon and others using germ-free mice colonized with conventional gut flora or B. thetaiotaomicron suggested that the gut flora contribute to carbohydrate and lipid
Gut flora induce intestinal development further enhancing nutrition
Using colonic bacteria or B. thetaiotaomicron colonization of germ-free mice as an experimental model, several lines of evidence support the hypothesis that our gut flora promote intestinal development that may serve to further enhance the host's nutrition. First, B. thetaiotaomicron colonization induces expression of sodium/glucose transporters (Sglt1) in the intestinal epithelium providing assistance in uptake of the glucose liberated by the metabolic activities of the gut flora [18]. Second,
Gut flora induce gut innate and adaptive immunity
Germ-free mice have an underdeveloped mucosal immune system with small lymphoid follicles, few IgA-secreting plasma cells and reduced submucosal T cell populations including CD4+ and intraepithelial CD8+ lymphocytes [20], [21]. Stimulation of the development of the intestinal immune system by the gut flora occurs over a few months [5], [22]. Conventional gut flora, but not B. thetaiotaomicron alone, have been shown to induce expression and secretion by Paneth cells of angiogenin-4, a
Summary and conclusions
A renaissance is underway regarding our understanding of the contributions of our flora to human health and development. The sequencing of the B. thetaiotaomicron [16] and B. fragilis genomes [10], [11], microarray analyses and new animal models with their genetic variants have begun to provide a sophisticated understanding of the everyday interactions of the gut flora and the intestinal epithelium. Together these data indicate that ‘commensals’, suggesting simple coexistence, is a poor term
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