Gastroenterology

Gastroenterology

Volume 136, Issue 1, January 2009, Pages 65-80
Gastroenterology

Reviews in Basic and Clinical Gastroenterology
Microbes in Gastrointestinal Health and Disease

https://doi.org/10.1053/j.gastro.2008.10.080Get rights and content

Most, if not all, animals coexist with a complement of prokaryotic symbionts that confer a variety of physiologic benefits. In humans, the interaction between animal and bacterial cells is especially important in the gastrointestinal tract. Technical and conceptual advances have enabled rapid progress in characterizing the taxonomic composition, metabolic capacity, and immunomodulatory activity of the human gut microbiota, allowing us to establish its role in human health and disease. The human host coevolved with a normal microbiota over millennia and developed, deployed, and optimized complex immune mechanisms that monitor and control this microbial ecosystem. These cellular mechanisms have homeostatic roles beyond the traditional concept of defense against potential pathogens, suggesting these pathways contribute directly to the well-being of the gut. During their coevolution, the bacterial microbiota has established multiple mechanisms to influence the eukaryotic host, generally in a beneficial fashion, and maintain their stable niche. The prokaryotic genomes of the human microbiota encode a spectrum of metabolic capabilities beyond that of the host genome, making the microbiota an integral component of human physiology. Gaining a fuller understanding of both partners in the normal gut-microbiota interaction may shed light on how the relationship can go awry and contribute to a spectrum of immune, inflammatory, and metabolic disorders and may reveal mechanisms by which this relationship could be manipulated toward therapeutic ends.

Section snippets

Evolutionary History of the Gut and Its Associates

Eukaryotes existed in close alliance with microbes even before the appearance of multicellular life.2, 3, 4 Indeed, the very nature of the ancestral eukaryotic animal cell was radically changed by the capture and co-option of endosymbiotic prokaryotes that had the biochemical/metabolic capacity for oxidative phosphorylation, resulting in the formation of the mitochondria, intracellular organelles that are vital and defining features of eukaryotic animal cells.5 Symbiotic relationships, by

Overview of Human Microbiota

The human normal flora, or microbiota, is vast, both in its absolute quantitative mass and its qualitative diversity. A detailed inventory of the normal microbiota was long considered nearly unattainable by conventional microbiologic techniques; however, recent initiatives utilizing high-throughput sequencing and molecular taxonomic methodologies have greatly increased our understanding of the population composition, dynamics, and ecology of the gut microbiota (reviewed in several reports6, 49,

The Hygiene Hypothesis

Although it is important to consider the evolution of prokaryotic-eukaryotic interactions in understanding the mechanisms of gut-microbe interactions, clinical and epidemiologic studies have revealed the importance of this relationship to human health. Although great improvements in human health and longevity stem largely from 19th-century advances in sanitation and public health that reduced mortality from epidemics of infectious disease, recent observations have indicated that not all

Probiotics

There is currently much interest in deliberately manipulating the normal microbiota to accrue health benefits through an approach known as “probiotics.” Probiotics are defined as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.”151 Clearly, the conceptual basis of probiotics is well grounded.121, 137, 152 Therapeutic bacteria could presumably provide the same beneficial functions and activities that have evolved for the normal microbiota. For

Summary

An intricate symbiotic relationship has evolved between humans and microbes. We more fully understand the degree to which gastrointestinal biology is intertwined with microbiology, that the relationship between host and microbe is required for health, and that this relationship might be manipulated therapeutically (Table 2). Perhaps one day, an optimal microbiota will be considered one aspect of nutrition that is as amenable to intervention. Finally, with a fuller understanding of the

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    The authors disclose the following: Supported by National Institutes of Health grants DK071604 and AI064462.

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