Plasma vasoactive intestinal polypeptide (VIP) levels and intestinal ischaemia

Vasoactive intestinal polypeptide (VIP) is released into the portal circulation in large quantities by ischaemic bowel. In view of its known high concentration in the gut and potent vasoactive properties it may well be implicated in the pathogenesis of the serious haemodynamic changes produced by gut ischaemia.     

Molecular pathways driving disease-specific alterations of intestinal epithelial cells

Due to the fact that chronic inflammation as well as tumorigenesis in the gut is crucially impacted by the fate of intestinal epithelial cells, our article provides a comprehensive overview of the composition, function, regulation and homeostasis of the gut epithelium. In particular, we focus on those aspects which were found to be altered in the context of inflammatory bowel diseases or colorectal cancer and also discuss potential molecular targets for a disease-specific therapeutic intervention.     

Development and differentiation of the intestinal epithelium

The gastrointestinal tract develops from a simple tube to a complex organ with patterns of differentiation along four axes of asymmetry. The organ is composed of all three germ layers signaling to each other during development to form the adult structure. The gut epithelium is a constitutively developing tissue, constantly differentiating from a stem cell in a progenitor pool throughout the life of the organism. Signals from the adjacent mesoderm and between epithelial cells are required for normal orderly development/differentiation, homeostasis, and apoptosis. Embryonically important patterning factors are used during adult stages for these processes. Such critical pathways as the hedgehog, bone morphogenetic protein, Notch, Sox, and Wnt systems are used both in embryologic and adult times of gut development. We focus on and review the roles of these factors in gut epithelial cell development and differentiation.Received 18 October 2002; received after revision 18 December 2002; accepted 18 December 2002     

Mechanisms and consequences of intestinal dysbiosis

The composition of the gut microbiota is in constant flow under the influence of factors such as the diet, ingested drugs, the intestinal mucosa, the immune system, and the microbiota itself. Natural variations in the gut microbiota can deteriorate to a state of dysbiosis when stress conditions rapidly decrease microbial diversity and promote the expansion of specific bacterial taxa. The mechanisms underlying intestinal dysbiosis often remain unclear given that combinations of natural variations and stress factors mediate cascades of destabilizing events. Oxidative stress, bacteriophages induction and the secretion of bacterial toxins can trigger rapid shifts among intestinal microbial groups thereby yielding dysbiosis. A multitude of diseases including inflammatory bowel diseases but also metabolic disorders such as obesity and diabetes type II are associated with intestinal dysbiosis. The characterization of the changes leading to intestinal dysbiosis and the identification of the microbial taxa contributing to pathological effects are essential prerequisites to better understand the impact of the microbiota on health and disease.     

Metabolic changes during B cell differentiation for the production of intestinal IgA antibody

To sustain the bio-energetic demands of growth, proliferation, and effector functions, the metabolism of immune cells changes dramatically in response to immunologic stimuli. In this review, I focus on B cell metabolism, especially regarding the production of intestinal IgA antibody. Accumulating evidence has implicated not only host-derived factors (e.g., cytokines) but also gut environmental factors, including the possible involvement of commensal bacteria and diet, in the control of B cell metabolism during intestinal IgA antibody production. These findings yield new insights into the regulation of immunosurveillance and homeostasis in the gut.     

Possible influence of prolactin on intestinal hypertrophy in pregnant and lactating rats

Summary The increase in intestinal weights during lactation, and to a lesser extent during pregnancy, is inhibited by bromocriptin. This suggests that increased prolactin secretion might be responsible for gut hypertrophy during lactation.This work was supported by N.I.H. grant Ca-05388 and a Rockefeller Foundation Fellowship.The author is very grateful to Professor H.A. Bern for his useful suggestions. Professor E. Flückiger, Sandoz Ltd, kindly supplied the bromocriptin used in this study.     

Expression and functional importance of innate immune receptors by intestinal epithelial cells

Pattern recognition receptors are somatically encoded and participate in the innate immune responses of a host to microbes. It is increasingly acknowledged that these receptors play a central role both in beneficial and pathogenic interactions with microbes. In particular, these receptors participate actively in shaping the gut environment to establish a fruitful life-long relationship between a host and its microbiota. Commensal bacteria engage Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs) to induce specific responses by intestinal epithelial cells such as production of antimicrobial products or of a functional mucus layer. Furthermore, a complex crosstalk between intestinal epithelial cells and the immune system is initiated leading to a mature gut-associated lymphoid tissue to secrete IgA. Impairment in NLR and TLR functionality in epithelial cells is strongly associated with chronic inflammatory diseases such as Crohn’s disease, cancer, and with control of the commensal microbiota creating a more favorable environment for the emergence of new infections.     

Plasma enteroglucagon, peptide YY and gastrin in rats deprived of luminal nutrition, and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p less than 0.001) of intravenously fed (TPN) rats. Urogastrone-epidermal growth factor, (URO-EGF), reversed these changes. Although plasma enteroglucagon and gastrin levels showed a small increase with URO-EGF, this was far less than the gut tissue weight change, suggesting that it was unlikely that they were involved in modulating the proliferative response of the intestine to URO-EGF. Peptide tyrosine tyrosine (PYY) levels were however significantly increased by URO-EGF, indicating that PYY may possibly have a role in the modulation of intestinal cell proliferation.     

Bifidobacteria and the infant gut: an example of co-evolution and natural selection

Throughout the human life, the gut microbiota interacts with us in a number of different ways, thereby influencing our health status. The acquisition of such an interactive gut microbiota commences at birth. Medical and environmental factors including diet, antibiotic exposure and mode of delivery are major factors that shape the composition of the microbial communities in the infant gut. Among the most abundant members of the infant microbiota are species belonging to the Bifidobacterium genus, which are believed to confer beneficial effects upon their host. Bifidobacteria may be acquired directly from the mother by vertical transmission and their persistence in the infant gut is associated with their saccharolytic activity toward glycans that are abundant in the infant gut. Here, we discuss the establishment of the infant gut microbiota and the contribution of bifidobacteria to this early life microbial consortium.     

Implication of gut microbiota metabolites in cardiovascular and metabolic diseases

Evidence from the literature keeps highlighting the impact of mutualistic bacterial communities of the gut microbiota on human health. The gut microbita is a complex ecosystem of symbiotic bacteria which contributes to mammalian host biology by processing, otherwise, indigestible nutrients, supplying essential metabolites, and contributing to modulate its immune system. Advances in sequencing technologies have enabled structural analysis of the human gut microbiota and allowed detection of changes in gut bacterial composition in several common diseases, including cardiometabolic disorders. Biological signals sent by the gut microbiota to the host, including microbial metabolites and pro-inflammatory molecules, mediate microbiome–host genome cross-talk. This rapidly expanding line of research can identify disease-causing and disease-predictive microbial metabolite biomarkers, which can be translated into novel biodiagnostic tests, dietary supplements, and nutritional interventions for personalized therapeutic developments in common diseases. Here, we review results from the most significant studies dealing with the association of products from the gut microbial metabolism with cardiometabolic disorders. We underline the importance of these postbiotic biomarkers in the diagnosis and treatment of human disorders.     

Intestinal epithelial barrier and mucosal immunity

Regulated mechanisms sustain the ability of the gut immune system to discriminate harmless food antigens (Ag) and commensal bacteria from pathogenic microorganisms, resulting in tolerance versus protective immunity, respectively. Antigens of the gut commensals are not simply ignored, but rather trigger an active immunosuppressive process, more commonly known as oral tolerance, which prevents the outcome of immunopathology. Both intrinsic properties of the gut microenvironment and cellular actors, as well as peripheral events induced by systemic dissemination of oral Ag, promote the induction of regulatory mechanisms that ensure maintenance of gut homeostasis. The aim of this review is to provide a synthetic update on the mechanisms of oral tolerance, with particular emphasis on the complex interplay between regulatory CD4+ T cells, dendritic cells and the gut microenvironment.     

Molecular dialogue between the human gut microbiota and the host: a Lactobacillus and Bifidobacterium perspective

The human gut represents a highly complex ecosystem, which is densely colonized by a myriad of microorganisms that influence the physiology, immune function and health status of the host. Among the many members of the human gut microbiota, there are microorganisms that have co-evolved with their host and that are believed to exert health-promoting or probiotic effects. Probiotic bacteria isolated from the gut and other environments are commercially exploited, and although there is a growing list of health benefits provided by the consumption of such probiotics, their precise mechanisms of action have essentially remained elusive. Genomics approaches have provided exciting new opportunities for the identification of probiotic effector molecules that elicit specific responses to influence the physiology and immune function of their human host. In this review, we describe the current understanding of the intriguing relationships that exist between the human gut and key members of the gut microbiota such as bifidobacteria and lactobacilli, discussed here as prototypical groups of probiotic microorganisms.     

Microbiome,probiotics and neurodegenerative diseases: deciphering the gut brain axis

The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastrointestinal tract communicates with the central nervous system through the gut–brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecular communication network that link systemic imbalances with the development of neurodegeneration including insulin regulation, fat metabolism, oxidative markers and immune signaling. Age is a common factor in the development of neurodegenerative disease and probiotics prevent many harmful effects of aging such as decreased neurotransmitter levels, chronic inflammation, oxidative stress and apoptosis—all factors that are proven aggravators of neurodegenerative disease. Indeed patients with Parkinson’s and Alzheimer’s diseases have a high rate of gastrointestinal comorbidities and it has be proposed by some the management of the gut microbiota may prevent or alleviate the symptoms of these chronic diseases.     

Degradation of bacterial lipopolysaccharide by gut juice os the snail Helix pomatia.

Lipopolysaccharides from several bacteria were selectively degarded by gut juice of the snail Helix pomatia with extensive loss of anticomplementary activity and changes in the electrophoretic pattern in polyacrylamide gels. The gut juice had little effect on ketodeoxyoctonate content or immunodominant sugars. The lipid A moiety of the lipopolysaccharide appeared to be the main site of attack.     

Voices from within: gut microbes and the CNS

Recent advances in research have greatly increased our understanding of the importance of the gut microbiota. Bacterial colonization of the intestine is critical to the normal development of many aspects of physiology such as the immune and endocrine systems. It is emerging that the influence of the gut microbiota also extends to modulation of host neural development. Furthermore, the overall balance in composition of the microbiota, together with the influence of pivotal species that induce specific responses, can modulate adult neural function, peripherally and centrally. Effects of commensal gut bacteria in adult animals include protection from the central effects of infection and inflammation as well as modulation of normal behavioral responses. There is now robust evidence that gut bacteria influence the enteric nervous system, an effect that may contribute to afferent signaling to the brain. The vagus nerve has also emerged as an important means of communicating signals from gut bacteria to the CNS. Further understanding of the mechanisms underlying microbiome–gut–brain communication will provide us with new insight into the symbiotic relationship between gut microbiota and their mammalian hosts and help us identify the potential for microbial-based therapeutic strategies to aid in the treatment of mood disorders.     

Degradation of bacterial lipopolysaccharide by gut juice of the snailHelix pomatia

Summary Lipopolysaccharides from several bacteria were selectively degraded by gut juice of the snailHelix pomatia with extensive loss of anticomplementary activity and changes in the electrophoretic pattern in polyacrylamide gels. The gut juice had little effect on ketodeoxyoctonate content or immunodominant sugars. The lipid A moiety of the lipopolysaccharide appeared to be the main site of attack.     

Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Insects mostly develop on decaying and contaminated organic matter and often serve as vectors of biologically transmitted diseases by transporting microorganisms to the plant and animal hosts. As such, insects are constantly ingesting microorganisms, a small fraction of which reach their epithelial surfaces, mainly their digestive tract, where they can establish relationships ranging from symbiosis to mutualism or even parasitism. Understanding the tight physical, genetic, and biochemical interactions that takes place between intestinal epithelia and either resident or infectious microbes has been a long-lasting objective of the immunologist. Research in this field has recently been re-vitalized with the development of deep sequencing techniques, which allow qualitative and quantitative characterization of gut microbiota. Interestingly, the recent identification of regenerative stem cells in the Drosophila gut together with the initial characterization of Drosophila gut microbiota have opened up new avenues of study aimed at understanding the mechanisms that regulate the dialog between the Drosophila gut epithelium and its microbiota of this insect model. The fact that some of the responses are conserved across species combined with the power of Drosophila genetics could make this organism model a useful tool to further elucidate some aspects of the interaction occurring between the microbiota and the human gut.     

Histoautoradiographic study of two target organs (epididymis and femoral glands) after injection of 3H testosterone in a non-mammalian vertebrae, the viviparous lizard]

After 3H testosterone injection into castrated males of the Lizard Lacerta vivipara, the radioactive compound is detected by radioautography of epididymis, femoral glands, gut and liver. Between 1 hr. 30 min. to 12 hrs. of retention the 3H material concentrates progressively into nuclei of the glandular cells of epididymis and femoral organs although no particular concentration occurs in gut and liver cells. This submammalian model is consistent with those previously described for mammals.