Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

Lee R Hagey,Nicolas Vidal,Alan F Hofmann,Matthew D Krasowski

doi:10.1186/1471-2148-10-133

Lee R Hagey, Nicolas Vidal + Show 2 more

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https://doi.org/10.1186/1471-2148-10-133

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Abstract

BackgroundBile salts are the major end-metabolites of cholesterol and are also important in lipid and protein digestion and in influencing the intestinal microflora. We greatly extend prior surveys of bile salt diversity in both reptiles and mammals, including analysis of 8,000 year old human coprolites and coprolites from the extinct Shasta ground sloth (Nothrotherium shastense).ResultsWhile there is significant variation of bile salts across species, bile salt profiles are generally stable within families and often within orders of reptiles and mammals, and do not directly correlate with differences in diet. The variation of bile salts generally accords with current molecular phylogenies of reptiles and mammals, including more recent groupings of squamate reptiles. For mammals, the most unusual finding was that the Paenungulates (elephants, manatees, and the rock hyrax) have a very different bile salt profile from the Rufous sengi and South American aardvark, two other mammals classified with Paenungulates in the cohort Afrotheria in molecular phylogenies. Analyses of the approximately 8,000 year old human coprolites yielded a bile salt profile very similar to that found in modern human feces. Analysis of the Shasta ground sloth coprolites (approximately 12,000 years old) showed the predominant presence of glycine-conjugated bile acids, similar to analyses of bile and feces of living sloths, in addition to a complex mixture of plant sterols and stanols expected from an herbivorous diet.ConclusionsThe bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution, with some bile salt modifications only found within single groups such as marsupials. Analysis of the evolution of bile salt structures in different species provides a potentially rich model system for the evolution of a complex biochemical pathway in vertebrates. Our results also demonstrate the stability of bile salts in coprolites preserved in arid climates, suggesting that bile salt analysis may have utility in selected paleontological research.

Highlights

Bile salts are the major end-metabolites of cholesterol and are important in lipid and protein digestion and in influencing the intestinal microflora
We grouped bile salts into three broad types (C27 bile alcohols, C27 bile acids, and C24 bile acids), which allowed us to classify each species into one of six categories based on which one or two bile salt types are present at 10% or greater of the biliary bile salt pool [10]: class I, C27 bile alcohols only; class II, C27 bile alcohols + C27 bile acids; class III, C27 bile alcohols + C24 bile acids; class IV, C27 bile acids only; class V, C27 bile acids + C24 bile acids; and class VI, C24 bile acids only
The bile salt profiles of all species analyzed are in Additional File 1 and Additional File 2, with the bile salt class indicated for each species

Summary

Introduction

Bile salts are the major end-metabolites of cholesterol and are important in lipid and protein digestion and in influencing the intestinal microflora. Water-soluble end-metabolites of cholesterol that facilitate intestinal absorption of lipids, enhance proteolytic cleavage of dietary proteins, and exert potent antimicrobial activity in the small intestine [1]. The two basic structural components of bile salts are the 19-carbon (C19) steroid nucleus and a side-chain (Figure 1). In all bile salts characterized to date, the four-ring cyclopentanophenanthrene ('steroid') nucleus (with rings labelled A, B, C, and D as in cholesterol in Figure 1B) is fully saturated (i.e., the cholesterol double bond at C5-C6 has been reduced). The A/B ring juncture is variable, being cis in most bile salts but trans in some species (e.g., jawless fish, lobe-finned fish, agamid lizards), a shift that greatly influences the overall shape of the steroid nucleus. All bile salts have a hydroxyl group at C-3 (like cholesterol) and at C-7, because cholesterol 7α-

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