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INTRODUCTION

For unicellular organisms that exist in a sea of nutrients, it is possible to satisfy nutritional requirements simply with the activity of membrane transport proteins that permit the uptake of specific molecules into the cytosol. However, for multicellular organisms, including humans, the challenges of delivering nutrients to appropriate sites in the body are significantly greater, particularly if the organisms are terrestrial. Further, most of the food we eat is in the form of macromolecules, and even when these are digested to their component monomers, most of the end products are water-soluble and do not readily cross cell membranes (a notable exception are the constituents of dietary lipids). Thus, the gastrointestinal system has evolved to permit nutrient acquisition and assimilation into the body, while prohibiting the uptake of undesirable substances (toxins and microbial products, as well as microbes themselves). The latter situation is complicated by the fact that the intestine maintains a lifelong relationship with a rich microbial ecosystem residing in its lumen, a relationship that is largely mutually beneficial if the microbes are excluded from the systemic compartment.

The intestine is a continuous tube that extends from mouth to anus and is formally contiguous with the external environment. A single cell layer of columnar epithelial cells comprises the semipermeable barrier across which controlled uptake of nutrients takes place. Various glandular structures empty into the intestinal lumen at points along its length, providing for digestion of food components, signaling to distal segments, and regulation of the microbiota. There are also important motility functions that move the intestinal contents and resulting waste products along the length of the gut, and a rich innervation that regulates motility, secretion, and nutrient uptake, in many cases in a manner that is independent of the central nervous system (CNS). There are also a large number of endocrine cells that release hormones that work together with neurotransmitters to coordinate overall regulation of the gastrointestinal system. In general, there is a considerable redundancy of control systems as well as excess capacity for nutrient digestion and uptake. This served humans well in ancient times when food sources were scarce but may now contribute to the modern epidemic of obesity.

The liver, while playing important roles in whole body metabolism, is usually considered a part of the gastrointestinal system for two main reasons. First, it provides for excretion from the body of lipid-soluble waste products that cannot enter the urine. These are secreted into the bile and thence into the intestine to be excreted with the feces. Second, the blood flow draining the intestine is arranged such that substances that are absorbed pass first through the liver, allowing for the removal and metabolism of any toxins that have inadvertently been taken up, as well as clearance of particulates, such as small numbers of enteric bacteria.

In this section, the function of the gastrointestinal system and liver will be considered, and the ways ...

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