Coral microbiology is an emerging field, driven largely by a desire to understand, and ultimately prevent, the worldwide destruction of coral reefs. The mucus layer, skeleton and tissues of healthy corals all contain large populations of eukaryotic algae, bacteria and archaea. These microorganisms confer benefits to their host by various mechanisms, including photosynthesis, nitrogen fixation, the provision of nutrients and infection prevention. Conversely, in conditions of environmental stress, certain microorganisms cause coral bleaching and other diseases. Recent research indicates that corals can develop resistance to specific pathogens and adapt to higher environmental temperatures. To explain these findings the coral probiotic hypothesis proposes the occurrence of a dynamic relationship between symbiotic microorganisms and corals that selects for the coral holobiont that is best suited for the prevailing environmental conditions. Generalization of the coral probiotic hypothesis has led us to propose the hologenome theory of evolution.

Phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) is a key enzyme in the synthesis of glucose in the liver and kidney and of glyceride-glycerol in white adipose tissue and the small intestine. The gene for the cytosolic form of PEPCK (PEPCK-C) is acutely regulated by a variety of dietary and hormonal signals, which result in alteration of synthesis of the enzyme. Major factors that increase PEPCK-C gene expression include cyclic AMP, glucocorticoids, and thyroid hormone, whereas insulin inhibits this process. PEPCK-C is absent in fetal liver but appears at birth, concomitant with the capacity for gluconeogenesis. Regulatory elements that control transcription of the PEPCK-C gene in liver, kidney, and adipose tissue have been delineated, and many of the transcription factors that bind to these elements have been identified. Transgenic mice have been especially useful in elucidating the physiological roles of specific sequence elements in the PEPCK-C gene promoter and in demonstrating the key role played at these sites by the isoforms of CAAT/enhancer binding protein in patterning of PEPCK-C gene expression during the perinatal period. The PEPCK-C gene provides a model for the metabolic control of gene transcription.

SummaryEmerging diseases have been responsible for the death of about 30% of corals worldwide during the last 30 years. Coral biologists have predicted that by 2050 most of the world's coral reefs will be destroyed. This prediction is based on the assumption that corals can not adapt rapidly enough to environmental stress-related conditions and emerging diseases. Our recent studies of the Vibrio shiloi/Oculina patagonica model system of the coral bleaching disease indicate that corals can indeed adapt rapidly to changing environmental conditions by altering their population of symbiotic bacteria. These studies have led us to propose the Coral Probiotic Hypothesis. This hypothesis posits that a dynamic relationship exists between symbiotic microorganisms and environmental conditions which brings about the selection of the most advantageous coral holobiont. Changing their microbial partners would allow the corals to adapt to changing environmental conditions more rapidly (days to weeks) than via mutation and selection (many years). An important outcome of the Probiotic Hypothesis would be development of resistance of the coral holobiont to diseases. The following evidence supports this hypothesis: (i) Corals contain a large and diverse bacterial population associated with their mucus and tissues; (ii) the coral-associated bacterial population undergoes a rapid change when environmental conditions are altered; and (iii) although lacking an adaptive immune system (no antibodies), corals can develop resistance to pathogens. The Coral Probiotic Hypothesis may help explain the evolutionary success of corals and moderate the predictions of their demise.

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Transcription of the gene for PEPCK-C occurs in a number of mammalian tissues, with highest expression occurring in the liver, kidney cortex, and white and brown adipose tissue. Several hormones and other factors, including glucagon, epinephrine, insulin, glucocorticoids and metabolic acidosis, control this process in three responsive tissues, liver, adipose tissue, and kidney cortex. Expression of the gene in these three tissues in regulated in a different manner, responding to the specific physiological role of the tissue. The PEPCK-C gene promoter has been extensively studied and a number of regulatory regions identified that bind key transcription factors and render the gene responsive to hormonal and dietary stimuli. This review will focus on the control of transcription for the gene, with special emphasis on our current understanding of the transcription factors that are involved in the response of PEPCK-C gene in specific tissues. We have also reviewed the biological function of PEPCK-C in each of the tissues discussed in this review, in order to place the control of PEPCK-C gene transcription in the appropriate physiological context. Because of its extraordinary importance in mammalian metabolism and its broad pattern of tissue-specific expression, the PEPCK-C gene has become a model for studying the biological basis of the control of gene transcription.

Cholecystectomy, surgical removal of the gallbladder, changes bile flow to the intestine and can therefore alter the bidirectional interactions between bile acids (BAs) and the intestinal microbiota. We quantified and correlated BAs and bacterial community composition in gallstone patients scheduled for cholecystectomy before and after the procedure, using gas-liquid chromatography and 16S rRNA amplicon sequencing, followed by quantitative real-time polymerase chain reaction of the phylum Bacteroidetes. Gallstone patients had higher overall concentrations of faecal BAs and a decreased microbial diversity, accompanied by a reduction in the beneficial genus Roseburia and an enrichment of the uncultivated genus Oscillospira, compared with controls. These two genera may thus serve as biomarkers for symptomatic gallstone formation. Oscillospira was correlated positively with secondary BAs and negatively with primary BAs, while the phylum Bacteroidetes showed an opposite trend. Cholecystectomy resulted in no substantial change in patients' faecal BAs. However, bacterial composition was significantly altered, with a significant increase in the phylum Bacteroidetes. Given that cholecystectomy has been associated with a higher risk of colorectal cancer and that members of the Bacteroidetes are increased in that disease, microbial consequences of cholecystectomy should be further explored.

Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision of 3-glycerophosphate, which may be supplied by the metabolism of glucose or by glyceroneogenesis, the de novo synthesis of 3-glycerophosphate from sources other than hexoses or glycerol. The importance of glyceroneogenesis in adipose tissue was assessed in mice by specifically eliminating the expression of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C), an enzyme that plays a pivotal role in the pathway. To accomplish this, we mutated the binding site for the peroxisome proliferator-activated receptor ␥ (PPAR␥) called the peroxisome proliferator-activated receptor element (PPARE), in the 5 flanking region of the PEPCK-C gene in the mouse by homologous recombination. The mutation abolished expression of the gene in white adipose tissue and considerably reduced its expression in brown adipose tissue, whereas the level of PEPCK-C mRNA in liver and kidney remained normal. Epididymal white adipose tissue from these mice had a reduced triglyceride deposition, with 25% of the animals displaying lipodystrophy. There was also a greatly reduced level of lipid accumulation in brown adipose tissue. A strong correlation between the hepatic content of triglycerides and the size of the epididymal fat pad in PPARE ؊/؊ mice suggests that hepatic triglyceride synthesis predominantly utilizes free fatty acids derived from the adipose tissue. Unlike other models, PPARE ؊/؊ mice with lipodystrophy did not exhibit the lipodystrophy-associated features of diabetes and displayed only moderate hyperglycemia. These studies establish the importance of the PPARE site for PEPCK-C gene expression in adipose tissue and the role of PEPCK-C in the regulation of glyceroneogenesis, a pathway critical for maintaining the deposition of triglycerides in adipose tissue.

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