Brain, Gut and Skin Peptide Hormones in Lower Vertebrates

Understanding of peptide hormone evolution rests primarily onstructural information, either direct or inferred. We summarizestudies of fishes and amphibians to provide initial informationwithin the vertebrate lineage for selected peptides which exhibitvarying structural heterogeneity. For these peptides, thyrotropin-releasinghormone, somatostatin, luteinizing hormone-releasing hormoneand cholecystokinin related peptides manifest increasing diversification.Members of these peptide families are found distributed amonga variety of tissues (e.g., brain, gut, skin, retina, sympatheticnervous system), yet the number of genes encoding for individualtypes of peptides is presently uncertain. We emphasize the needfor additional structural information, for a more thorough anddiverse taxonomic investigation within the vertebrate lineage,and for specification of those genetic elements which ultimatelydetermine evolutionary opportunities for peptide evolution.     

Gut,Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders

It has become apparent that the molecular and biochemical integrity of interactive families, genera, and species of human gut microflora is critically linked to maintaining complex metabolic and behavioral processes mediated by peripheral organ systems and central nervous system neuronal groupings. Relatively recent studies have established intrinsic ratios of enterotypes contained within the human microbiome across demographic subpopulations and have empirically linked significant alterations in the expression of bacterial enterotypes with the initiation and persistence of several major metabolic and psychiatric disorders. Accordingly, the goal of our review is to highlight potential thematic/functional linkages of pathophysiological alterations in gut microbiota and bidirectional gut–brain signaling pathways with special emphasis on the potential roles of gut dysbiosis on the pathophysiology of psychiatric illnesses. We provide critical discussion of putative thematic linkages of Parkinson’s disease (PD) data sets to similar pathophysiological events as potential causative factors in the development and persistence of diverse psychiatric illnesses. Finally, we include a concise review of preclinical paradigms that involve immunologically–induced GI deficits and dysbiosis of maternal microflora that are functionally linked to impaired neurodevelopmental processes leading to affective behavioral syndromes in the offspring.     

Gut fungi

Herbivores consume large quantities of cellulose and other plant cell wall (fibre) carbohydrates yet generally lack the enzymes to digest them. This has led to the evolution of specialized portions of the gut, such as the rumen and caecum, which contain large populations of digestive anaerobic microorganisms. Diverse bacteria and protists from this environment have been studied for over a hundred years but it is only recently that a significant population of highly specialized flagellate fungi have been identified. These fungi are important in fibre digestion. Their diversity, properties, activities, phylogeny and possible economic significance are the subjects of this review.     

Effect of Antibiotics on Gut Microbiota,Gut Hormones and Glucose Metabolism

Objective

The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans.

Methods

Meal tests with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition.

Results

Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release.

Conclusion

As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males.

Trial Registration

clinicaltrials.gov NCT01633762     

High-Fat Feeding Impairs Nutrient Sensing and Gut Brain Integration in the Caudomedial Nucleus of the Solitary Tract in Mice

Hyperphagic obesity is characterized in part by a specific increase in meal size that contributes to increased daily energy intake, but the mechanisms underlying impaired activity of meal size regulatory circuits, particularly those converging at the caudomedial nucleus of the solitary tract in the hindbrain (cmNTS), remain poorly understood. In this paper, we assessed the consequences of high-fat (HF) feeding and diet-induced obesity (DIO) on cmNTS nutrient sensing and metabolic integration in the control of meal size. Mice maintained on a standard chow diet, low-fat (LF) diet or HF diet for 2 weeks or 6 months were implanted with a bilateral brain cannula targeting the cmNTS. Feeding behavior was assessed using behavioral chambers and meal-pattern analysis following cmNTS L-leucine injections alone or together with ip CCK. Molecular mechanisms implicated in the feeding responses were assessed using western blot, immunofluorescence and pharmacological inhibition of the amino acid sensing mTORC1 pathway (mammalian target of rapamycin complex 1). We found that HF feeding blunts the anorectic consequences of cmNTS L-leucine administration. Increased baseline activity of the L-leucine sensor P70 S6 kinase 1 and impaired L-leucine-induced activation of this pathway in the cmNTS of HF-fed mice indicate that HF feeding is associated with an impairment in cmNTS mTOR nutritional and hormonal sensing. Interestingly, the acute orexigenic effect of the mTORC1 inhibitor rapamycin was preserved in HF-fed mice, supporting the assertion that HF-induced increase in baseline cmNTS mTORC1 activity underlies the defect in L-leucine sensing. Last, the synergistic feeding-suppressive effect of CCK and cmNTS L-leucine was abrogated in DIO mice. These results indicate that HF feeding leads to an impairment in cmNTS nutrient sensing and metabolic integration in the regulation of meal size.     

Gut and Root Microbiota Commonalities

Animal guts and plant roots have absorption roles for nutrient uptake and converge in harboring large, complex, and dynamic groups of microbes that participate in degradation or modification of nutrients and other substances. Gut and root bacteria regulate host gene expression, provide metabolic capabilities, essential nutrients, and protection against pathogens, and seem to share evolutionary trends.     

肠道微生态与肥胖

人的肠道是一个丰富的微生态系统,含有100万亿多的微生物,种类多达500-1000个,这些微生物的基因总数是人体基因组所含基因总数的100倍。肠道微生物丛的组成种类和数量与宿主的肥胖有关,无菌小鼠含有的脂肪量比正常饲养小鼠低42％,如果将微生物丛植入到无菌小鼠体内后,导致脂肪总量增加57％。提示肠道微生物丛可以明显的促进小鼠对热能的摄人,促使脂肪的沉积,触动全身性炎症反应。因此,对肥胖的治疗可以采用益生菌和益生元来调节肠道微生物丛的状态以期获得治疗效果。本研究述及肠道微生丛对宿主肥胖及其代谢机制的研究进展。     

肠道稳态与代谢综合征

代谢综合征(metabolic syndrome,MS)是具有多样临床表现的物质代谢紊乱,包括肥胖和胰岛素抵抗等。它能增加糖尿病和心血管的发病率。目前它的病因尚不明确,与环境、免疫、遗传等因素有关。研究表明代谢综合征患者肠道菌群结构较正常人有所改变,肠道稳态被打破。宿主共生菌在正常生理条件下,参与到宿主的物质代谢、营养吸收、免疫反应等过程中,同时其也受宿主基因、营养情况和生活方式的影响。不断深入了解宿主和肠道菌群之间的作用关系,能有效提出具有针对性的治疗代谢综合征的个性化防治策略。     

Gut triglyceride production

Our knowledge of how the body absorbs triacylglycerols (TAG) from the diet and how this process is regulated has increased at a rapid rate in recent years. Dietary TAG are hydrolyzed in the intestinal lumen to free fatty acids (FFA) and monoacylglycerols (MAG), which are taken up by enterocytes from their apical side, transported to the endoplasmic reticulum (ER) and resynthesized into TAG. TAG are assembled into chylomicrons (CM) in the ER, transported to the Golgi via pre-chylomicron transport vesicles and secreted towards the basolateral side. In this review, we mainly focus on the roles of key proteins involved in uptake and intracellular transport of fatty acids, their conversion to TAG and packaging into CM. We will also discuss intracellular transport and secretion of CM. Moreover, we will bring to light few factors that regulate gut triglyceride production. Furthermore, we briefly summarize pathways involved in cholesterol absorption. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.     

Gut triglyceride production

Our knowledge of how the body absorbs triacylglycerols (TAG) from the diet and how this process is regulated has increased at a rapid rate in recent years. Dietary TAG are hydrolyzed in the intestinal lumen to free fatty acids (FFA) and monoacylglycerols (MAG), which are taken up by enterocytes from their apical side, transported to the endoplasmic reticulum (ER) and resynthesized into TAG. TAG are assembled into chylomicrons (CM) in the ER, transported to the Golgi via pre-chylomicron transport vesicles and secreted towards the basolateral side. In this review, we mainly focus on the roles of key proteins involved in uptake and intracellular transport of fatty acids, their conversion to TAG and packaging into CM. We will also discuss intracellular transport and secretion of CM. Moreover, we will bring to light few factors that regulate gut triglyceride production. Furthermore, we briefly summarize pathways involved in cholesterol absorption. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.