Current Protein and Peptide Science - Volume 16, Issue 7, 2015

Alpha-Ketoglutarate (AKG) is a biological substance that plays important roles in cell metabolism and physiology. AKG is synthesized from glucose or oxaloacetate plus pyruvate. As an intermediate of the tricarboxylic acid cycle, AKG is essential for the oxidation of fatty acids, amino acids, and glucose. Extracellular AKG is a significant source of energy for cells of the gastrointestinal tract. As a precursor for the synthesis of glutamate and glutamine in multiple tissues (including liver, skeletal muscle, heart, brain, and white adipose tissue), AKG bridges carbohydrate and nitrogen metabolism for both conservation of amino acids and ammonia detoxification. Additionally, emerging evidence shows that AKG is a regulator of gene expression and cell signaling pathways (including the mammalian target of rapamycin and AMPactivated protein kinase). Thus, AKG is an attractive dietary supplement in animal and human nutrition to improve cellular energy status, immunity, and health.

Antimicrobial peptides (AMPs), produced by several species including bacteria, insects, amphibians and mammals as well as by chemical synthesis and genetically engineered microorganisms, are of great importance in maintaining normal gut homeostasis. AMPs exhibit a broad spectrum of antimicrobial activity and inhibit microbial cells by interaction with their membranes or by other mechanisms, such as inhibition of cell-wall synthesis or suppression of nucleic acid or protein synthesis. In addition to their direct antimicrobial functions, they have multiple roles in the stabilization of epithelial barrier integrity and function as potent immune regulators. The fate of AMPs in vivo is poorly understood, prompting the need for studying AMPs pharmacokinetics. This review summarizes the current knowledge about the basic biology of AMPs and discusses the features of AMPs in gut homeostasis and their relative mechanisms of action.

The mammalian gut, the site of digestion and nutrients absorption, harbors diverse microbes that play an essential role in maintaining physiological homeostasis of the gastrointestinal system. These commensal microbes are important for the normal development of the host immune system and alteration of the microbiota of gastrointestinal system has been found to play an important role in the development of obesity, metabolic syndromes such as type 2 diabetes, and cardiovascular diseases. Several recent studies with mouse models and in humans have demonstrated that intestinal microbiota has important role in host metabolism by regulating energy absorption and modulating the endocrine functions. A variety of nutrients and metabolites derived from commensal bacteria have been proved to be important regulators in improving gut barrier functions and immune homeostasis. Here we review current literature on the interactions between microbes and host in the Gastrointestinal (GI) tract and based on these interactions we proposed a hypothesis in which the microbiota interacts with the host gastrointestine through a gut-brainendocrine- immune system. By understanding this system, we should be in better position to develop treatment for metabolic diseases and inflammation in human and animals.

The bioactive peptides are protein fragments which have a positive impact on the intestinal homeostasis. Intestinal homeostasis depends on the diverse functions of intestinal barrier including the microbiological, physical, chemical and immunological barriers. Defects in intestinal barrier function are associated with intestinal diseases. In this review, we will present current knowledge of the crosstalk between bioactive peptides and intestinal barrier during gut homeostasis.

Soybean is widely utilized in the food and feed industries. However, soybean contains many anti-nutritional factors that limit its extended application. The two most important antigenic proteins are glycinin and β-conglycinin. When young animals are fed diets containing soybean protein, a small portion of undigested proteins enters the lymph and blood through gaps between the intestinal epithelial cells. These macromolecules have considerable antigenic activity and stimulate the immune system resulting in specific antigen-antibody reactions and T lymphoid cell-mediated delayed hypersensitivity. A current focus of research is to develop methods to decrease the immuno-reactivity of soybean proteins. Several strategies have been developed to prevent food allergies including those feed processing and plant breeding. The latest studies indicate that certain kinds of immuno-modulators, such as vitamin C and lipoic acid, may specifically block the IgE mediated anaphylaxis and these may provide new insight into the effective prevention of soybean-induced allergy and perhaps other food allergies. This review is divided into seven parts including (1) Allergenic proteins found in soybean; (2) Structure-function relationships of allergenic proteins in soybean; (3) Extraction, purification and detection of allergenic proteins in soybean; (4) Anaphylaxis induced by allergenic proteins in soybean; (5) The potential mechanism of soybean allergy; (6) Prevention and treatment of soybean allergy; (7) The effects of plant breeding on the antigenicity of allergen proteins in soybean. Being fully aware of the soy protein antigen and finding the methods to eliminate anaphylaxis induced by soybean proteins will help to significantly improve efficiency of soybean protein utilization.

The mucosal surfaces of the intestinal tract are constantly exposed to complex microbial communities that contain commensal microorganisms and potential pathogens. Therefore, hosts harbor multiple molecular mechanisms to modulate the gut innate immunity to achieve gut-microbe homeostasis. Pattern recognition receptors (PRRs), such as Toll-like receptor (TLR) and nucleotide oligomerization domain (NOD)-like receptor (NLR), play a key role in sensing pathogens and promoting the induction of innate effectors. Gut microbiota, through PRRs, can modulate the expression of genes involved in inflammatory responses and the production of antimicrobial peptides. In turn, the expression of PRRs affects the structure of gut microbiota in health or disease status. Deficiency in PRRs such as NOD2 and TLR5 can alter the gut microbiota composition in mice. The crosstalk between PRRs and microbiota connects the microbial action with the host response. This article outlines recent advances in the role of immune sensors in the gut microbiota balance and the related microbiota-host interaction.

The mammalian intestine harbors a mass of microorganisms that is essential to maintain intestinal epithelium homeostasis and health. However, some microbes can damage the epithelial mucosal barrier to utilize nutrients for their survival and growth. Autophagy is a highly conserved cellular process that targets cytoplasmic damaged organelles and some cellular molecules to lysosome for degradation. Accumulating studies have demonstrated that autophagy plays an important role in the innate immune system in response to different gut pathogens. For instance, autophagy can be induced to mediate the process of pathogenic infection during pathogens invasion. In this review, we mainly discuss the steps of autophagy pathway mediated by microbes and the role of autophagy in the gut pathogens clearance and evasion.

Dietary protein is a vital nutrient for humans and animals, which is primarily digested into peptides and free amino acids (FAAs) in the upper gastrointestine with the help of proteases. The products are absorbed by the enterocytes and are metabolized in different organs of body. Dietary protein, peptides and FAAs that escape digestion and absorption of the small intestine will enter the large intestine for further fermentation by the vast gut microbiota. Particularly, amino acid (AAs) metabolism by bacteria occurs via either deamination or decarboxylation reactions and generates short chain fatty acids (SCFAs) or amines, respectively. These metabolites elicit a wide range of biological functions via different receptors and mechanisms. This review discusses the interaction between protein metabolites and gastrointestine, illustrates regulation of intestinal motility and immune response by SCFAs and their receptors, and focuses on modulation of intestinal inflammation and signal transduction by biogenic amines (BAs) involving polyamines and monoamine neurotransmitters.

Homeostasis of the immune system depends on several factors. The gastrointestinal tract plays an important role in maintaining our immune system. With this aim, the intestinal immune system interacts with epithelial barrier molecules, especially tight junction proteins, that are key molecules involved in controlling paracellular permeability to increase the protection barrier against external antigens or possibly to respond to commensal microorganisms. During intestinal inflammatory diseases, the expression of innate immune receptors in intestinal epithelial cells and infiltration of immune cells are related, but it is still unclear how the immune system induces modulation of paracellular permeability. In this review, we provide an overview of the understanding of how the immune system modulates the expression of tight junctions to maintain the mucosal immune system.

Host defense peptides (HDPs) are of either myeloid or epithelial origin with antimicrobial and immunomodulatory functions. Due to HDP’s ability to physically disrupt bacterial cell membranes and profoundly regulate host innate and adaptive immunity, microbial resistance to these peptides is rare. As an important first line of defense, HDPs are mostly present in epithelial cells of the digestive, respiratory or urogenital tracts as well as in the granules of neutrophils, macrophages or intestinal secretory Paneth cells. HDPs are either directly released or inducibly expressed upon exposure to microbes or microbial products, although certain pathogens such as Shigella have evolved an ability to down-regulate HDP synthesis as an immune invasion strategy. Even if a majority of HDPs are induced by infection and inflammation, it is undesirable to augment HDP synthesis and host immunity using pathogen-associated molecular patterns because of an excessive inflammation that is usually accompanied. Recently, several different classes of small-molecule compounds have been identified with the capacity to specifically induce HDP synthesis without triggering extensive inflammatory response. A few HDPinducing compounds even synergize with each other in HDP induction. In this review, we summarized the recent progresses on transcriptional regulation of HDPs by infection and inflammation and by small-molecule compounds. We suggested the potential of dietary regulation of HDPs as a novel antibiotic-alternative strategy to antimicrobial therapy, as oral supplementation of HDP-inducing compounds has shown promise of preventing and controlling infections in humans and several animal species.