Type 2 diabetes and gut microbiome: at the intersection of known and unknown

The prevalence of metabolic syndrome is increasing rapidly across the globe. Though the prevalence of the disease is similar in population of upper middle income and high income countries, the age of affected population is lower in upper middle income countries. This is attributed to genetic as well as changing life style factors. The contributing factors for type 2 diabetes range from genetic/epigenetic disposal, intra uterine nutrition, dietary pattern to sedentary lifestyle. The role of the gut microbiota in metabolic disorders is increasingly gaining importance. Several studies have reported significant difference in the profile of the gut microbiota in Caucasian population considering obese and type 2 diabetic populations while limited number of studies are available on populations from the developing world. The metabolites from the gut microbes contribute to the gut barrier integrity and a compromised barrier leads to leakage of inflammatory mediators into systemic circulation and hence increases insulin resistance. Attempts have been made at correcting metabolic syndrome through dietary changes by altering the gut microbiota with some success. This report is an attempt to explain the hypothesis of compromised nutrition altering the gut microbiota, gut metabolites, gut barrier function, systemic inflammation and hence insulin response.Additional Search Terms: dysbiosys, gut metabolites, malnourishment, nutrition, obesity     

Upper gut motility of Hirschsprung's disease and its allied disorders in adults

BACKGROUND/AIMS: To clarify the significance of upper gut motility for Hirschsprung's disease and its allied disorders in adults, we studied the upper esophagogastroduodenal motility of adult patients with Hirschsprung's disease and its allied disorders such as hypoganglionosis and intestinal neuronal dysplasia. METHODOLOGY: Twelve patients (7 men and 5 women, aged between 20 and 55 years with a mean age of 39.6 years) with Hirschsprung's disease (2 cases) or its allied disorders (8 cases of hypoganglionosis and 2 cases of intestinal neuronal dysplasia) were studied. As a control, 15 healthy volunteers (8 men and 7 women aged between 27 and 69 years with a mean age of 49.0 years) were also examined. To obtain the upper gut motility in Hirschsprung's disease, hypoganglionosis, and intestinal neuronal dysplasia, we performed gastrointestinal transit time study, esophageal manometry, and gastroduodenal manometry. RESULTS: On gastrointestinal transit time, barium stagnated in the upper jejunum in 2 cases of hypoganglionosis, in the terminal ileum in one case of hypoganglionosis and intestinal neuronal dysplasia, and in the colon in the remaining patients. In two of the 12 cases of Hirschsprung's disease and its allied disorders such as hypoganglionosis and intestinal neuronal dysplasia, abnormal esophageal motilities, and absence of interdigestive migrating motor complex, phase III from the stomach were observed. These findings suggested that the entire digestive tract might have been affected in these two cases, i.e., these 2 patients had total gut involvement type of hypoganglionosis. CONCLUSIONS: Gastrointestinal transit time and upper esophagogastroduodenal manometry should be performed because of the relatively frequent association of upper gut dysmotilities with these disorders.     

Enteral IGF-I enhances fetal growth and gastrointestinal development in oesophageal ligated fetal sheep.

Infants with upper gut atresia often have impaired intrauterine growth and gut function. IGF-I is important in fetal growth and is contained in amniotic fluid. We therefore wanted to test the hypothesis that IGF-I infused into fetal gut would reverse the effects of an upper gut obstruction on gut structure and growth in fetal sheep. At 90 days gestation fetuses (n=6 per group) underwent oesophageal ligation, followed by continuous infusion of IGF-I (1-8 microgram/day) or saline into the gut beyond the ligation until 137 days. Controls underwent sham ligation only. Oesophageal ligation tended to reduce fetal body and organ weights. IGF-I treatment prevented this reduction and increased body length and spleen weight above those of controls. The decrease in bowel wall thickness induced by oesophageal ligation was also prevented by IGF-I treatment. Amniotic fluid IGF-I concentrations did not change over gestation and were higher in the IGF-I treated group. No change in fetal plasma IGF-I concentrations were detectable. We conclude that enterally administered IGF-I may enhance fetal growth and gut development in utero and that IGF-I in amniotic fluid may play a physiological role in gut development in the fetus.     

Systemic sclerosis and the gut

Gastrointestinal involvement (GI) is increasingly recognized as a major cause of both morbidity and mortality in systemic sclerosis (SSc). GI complications are common, second only to skin involvement, and affect up to 90% of patients. Although treatment modalities have changed little for upper gut symptoms such as GI reflux, there are emerging treatment modalities for the common lower gut symptoms (constipation and fecal incontinence), which will be reviewed. The important link between reflux and interstitial lung disease in SSc is also addressed. The aim of this review is to help the clinician understand and manage GI symptoms in SSc.     

Gut microbiota in the pathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic and relapsing inflammatory disorder of the intestine. Although its incidence is increasing globally, the precise etiology remains unclear and a cure for IBD has yet to be discovered. The most accepted hypothesis of IBD pathogenesis is that complex interactions between genetics, environmental factors, and the host immune system lead to aberrant immune responses and chronic intestinal inflammation. The human gut harbors a complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. The gut microbiota has physiological functions associated with nutrition, the immune system, and defense of the host. Recent advances in next-generation sequencing technology have identified alteration of the composition and function of the gut microbiota, which is referred to as dysbiosis, in IBD. Clinical and experimental data suggest dysbiosis may play a pivotal role in the pathogenesis of IBD. This review is focused on the physiological function of the gut microbiota and the association between the gut microbiota and pathogenesis in IBD. In addition, we review the therapeutic options for manipulating the altered gut microbiota, such as probiotics and fecal microbiota transplantation.     

Gut in diseases： Physiological elements and their clinical significance

The intestinal barrier function of GI tract is very important in the body except for the function of digestion and absorption. The functional status of gut barrier basically reflects the stress severity when body suffers from trauma and various stimulations. Many harmful factors such as drugs, illnesses, trauma and burns can damage the gut barrier, which can lead to the barrier dysfunction and bacterial/endotoxin translocation. The paper discusses and reviews the concepts, anatomy, pathophysiology of gut barrier and its clinical relations.     

Gut Microbiota and the Pathogenesis of Insulin Resistance

Several reviews recently explored how the gut microbiota was able to control host energy metabolism, and thereby the development of adiposity. In this review, we focused on the state of the art that supports a link between the gut microbiota composition and activity, and the management of glycemia associated with overweight and diabetes. Several microbial-derived compounds are related to disturbances of glucose homeostasis including the gram-negative–derived lipopolysaccharides. Some nutrients with prebiotic properties, which escape the digestion in the upper part of the gut, modify the composition of the gut microbiota in favor of bacteria that could play a beneficial role on glucose homeostasis, namely by modulating the endocrine function of the gut, and by reinforcing the gut barrier. Adequate intervention studies in diabetic patients are required to assess the relevance of those experimental data for human health.     

Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism

Recent studies have revealed a close relationship between inflammatory and metabolic pathways, and inflammation is now recognized to have a major role in obesity and metabolic diseases such as insulin resistance and atherosclerosis. The human body is home to a large number of distinct microbial communities, with the densest population in the distal gut (the gut microbiota). Bacteria have long been known to activate inflammatory pathways, and recent data demonstrate that the gut microbiota may affect lipid metabolism and function as an environmental factor that influences the development of obesity and related diseases. Here, we review how the gut microbiota may affect metabolic diseases by activating the innate immune system.     

Nutritional immunomodulation of acute pancreatitis

Despite the great advances in our understanding of the pathophysiology of acute pancreatitis, no specific therapy has emerged, and treatment remains supportive. In patients with the severe form of the disease, in which mortality remains high at 20% to 30%, the function of the upper gastrointestinal tract is disturbed due to extrinsic compression by the inflamed and swollen pancreas, and normal eating is impossible. Such patients often develop multiple organ failure, necessitating intensive-care management and artificial ventilation for weeks on end. In this setting, protein catabolism will rapidly result in protein deficiency and further complications unless nutritional support is commenced. Recent studies have shown that, despite the risk of disease exacerbation through pancreatic stimulation, enteral feeding is more effective than parenteral feeding in improving outcome. Experimental studies suggest that this can be attributed to its content of specific immunomodulating nutrients, such as glutamine, arginine, and n-3 fatty acids, and by its stabilizing effect on the gut flora through the provision of prebiotics. Further studies are indicated to examine whether dietary enrichment with these substrates, along with regulation of the gut bacteria with probiotics, can improve outcome further.     

Intestinal permeation and gastrointestinal disease

The gastrointestinal tract constitutes one of the largest sites of exposure to the outside environment. The function of the gastrointestinal tract in monitoring and sealing the host interior from intruders is called the gut barrier. A variety of specific and nonspecific mechanisms are in operation to establish the host barrier; these include luminal mechanisms and digestive enzymes, the epithelial cells together with tight junctions in between them, and the gut immune system. Disruptions in the gut barrier follow injury from various causes including nonsteroidal anti-inflammatory drugs and oxidant stress, and involve mechanisms such as adenosine triphosphate depletion and damage to epithelial cell cytoskeletons that regulate tight junctions. Ample evidence links gut barrier dysfunction to multiorgan system failure in sepsis and immune dysregulation. Additionally, contribution of gut barrier dysfunction to gastrointestinal disease is an evolving concept and is the focus of this review. An overview of the evidence for the role of gut barrier dysfunction in disorders such as Crohn's disease, celiac disease, food allergy, acute pancreatitis, non-alcoholic fatty liver disease, and alcoholic liver disease is provided, together with critical insight into the implications of this evidence as a primary disease mechanism.     

Immunoglobulin A and liver diseases

Immunoglobulin A (IgA) is a major immunoglobulin isotype in the gut and plays a role in maintenance of gut homeostasis. Secretory IgA (SIgA) has multiple functions in the gut, such as to regulate microbiota composition, to protect intestinal epithelium from pathogenic microorganisms, and to help for immune-system development. The liver is the front-line organ that receives gut-derived products through the portal vein, implying that the liver could be severely affected by a disrupted intestinal homeostasis. Indeed, some liver diseases like alcoholic liver disease are associated with an altered composition of gut microbiota and increased blood endotoxin levels. Therefore, deficiency of SIgA function appears as a significant factor for the pathogenesis of liver diseases associated with altered gut microbiome. In this review, we describe SIgA functions on the gut microbiome and discuss the role of IgA for liver diseases, especially alcoholic liver disease and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

     

饮食干预对非酒精性脂肪性肝病肠道菌群的影响

非酒精性脂肪性肝病(NAFLD)的发生与遗传和环境密切相关,肠道菌群在其发生和发展中发挥了重要作用,调节肠道菌群已成为干预NAFLD的重要靶点之一.无论是饮食总量还是结构都会对肠道菌群产生直接且长期的影响.通过低脂饮食、增加饮食中不饱和脂肪酸或者增加难以吸收的多糖等方式调整饮食结构,可以有效调节肠道菌群并治疗NAFLD,但高蛋白饮食的作用还存在争议.     

Exercise has the guts: How physical activity may positively modulate gut microbiota in chronic and immune-based diseases

Limited animal and human research findings suggests that exercise might have a beneficial role for health gut. Cardiorespiratory fitness correlates with health-associated gut parameters such as taxonomic diversity and richness. Physical exercise may augment intestinal microbial diversity through several mechanisms including promotion of an anti-inflammatory state. Disease-associated microbial functions were linked to distinct taxa in previous studies of familial type 1 diabetes mellitus (T1D). An integrated multi-approach in the study of T1D, including physical exercise, is advocated. The present review explores how exercise might modulate gut microbiota and microbiome characteristics in chronic and immune-based diseases, given the demonstrated relationship between gut function and human health.     

Evolving concepts in functional gastrointestinal disorders: promising directions for novel pharmaceutical treatments

In recent years there has been an increasing appreciation of the complexity of functional gastrointestinal disorders. These represent a spectrum of conditions which may affect any part of the gastrointestinal tract in which there appears to be dysregulation of visceral function and afferent sensation and a strong association with emotional factors and stress. There is a clear psychological dimension, with up to 60% of irritable bowel syndrome (IBS) patients reported to have psychological co-morbidities and altered pain perception is also common in comparison with control populations. The role of the enteric nervous system, the sensory pathways and the brain as well as the influence of the latter on sympathetic and parasympathetic outflow have likewise attracted increasing interest and have led to exciting new methods to study their complex interactions. The concept of low-grade inflammation, such as might occur after infection, acting as a trigger for neuromuscular dysfunction has also led to the broad integrative hypotheses that help to explain the biopsychosocial dimensions seen in functional gastrointestinal disease. The multi-component model places a major emphasis on neurogastroenterology and enteric and neuro-immune interactions where new approaches to pharmacotherapy lie. Drugs may affect motility, visceral sensation and other aspects of gut function such as secretion or absorption. More particularly, however, has been the search for and attempts to influence important mediators of these primary gut functions. Such targets include serotonin and selected 5-HT receptors, which are involved in gut motility, visceral sensation and other aspects of gut function, CCK receptors which are involved in the mediation of pain in the gut and nociception in the CNS, opioid receptors involved in pain in the brain, spinal cord and periphery, muscarinic M3-receptors, substance P and neurokinin A and B receptors which are involved in motor adaptation and pain transmission in association with inflammation, gabba receptors involved in nociception and cannabinoid receptors which are involved in the control of acetyl choline release in the gut. With a better understanding of the structures and pathways involved in visceral perception and hyperalgesia, in the CNS, spinal cord and the gut and new pharmacological tools we will be better able to elucidate the neuropharmacology of visceral perception and its relationship to gut dysfunction. It is likely that there will be multiple therapeutic options based on the spectrum of abnormalities capable of causing the spectrum of symptoms of functional gastrointestinal disorders in any individual patient.     

Gastrointestinal transit in patients with idiopathic megarectum

PURPOSE: In patients with idiopathic megarectum, it is unknown whether abnormality is limited to the dilated large bowel or whether the upper gut is abnormal, as in the various forms of chronic intestinal pseudo-obstruction. This has important implications for treatment, especially surgery. METHODS: Ten patients (4 females; median age, 18 (range, 17–26) years) with idiopathic megarectum had contrast studies of the upper and lower gut, radioisotope (technetium-99m liquid and indium-111 solid phase) measurement of gastric, small-bowel, and colonic regional transit, and radiopaque marker colonic studies. RESULTS: All patients had a dilated large bowel. No patient had radiographic evidence of upper gut dilation. Four patients had normal and six patients had abnormally slow gastric emptying. Both the radioisotope scans and radiopaque marker studies showed abnormal colonic transit. Regions of delay corresponded with the region of dilated bowel. Symptoms of abdominal distention and bloating did not correspond to abnormalities of gastric emptying but rather with effectiveness of rectal evacuation. CONCLUSION: Patients with idiopathic megarectum have abnormal colonic transit, delay occurring predominantly in the dilated gut. Marker studies are less sensitive than isotope studies but provide adequate information for clinical purposes. Although motility abnormalities of the upper gut are common, symptoms correlate with large-bowel abnormalities.Jenny M. Gattuso was supported by the Alimentary Pharmacology and Therapeutics Trust and the British Digestive Foundation.Read at the meeting of the European Association of Nuclear Medicine, Brussels, Belgium, August 26 to 30, 1996.     

The gut microbiota keeps enteric glial cells on the move; prospective roles of the gut epithelium and immune system

The enteric nervous system (ENS) coordinates the major functions of the gastrointestinal tract. Its development takes place within a constantly changing environment which, after birth, culminates in the establishment of a complex gut microbiota. How such changes affect ENS development and its subsequent function throughout life is an emerging field of study that holds great interest but which is inadequately explored thus far. In this addendum, we discuss our recent findings showing that a component of the ENS, the enteric glial cell network that resides in the gut lamina propria, develops after birth and parallels the evolution of the gut microbiota. Importantly, this network was found to be malleable throughout life by incorporating new cells that arrive from the area of the gut wall in a process of directional movement which was controlled by the lumen gut microbiota. Finally, we postulate on the roles of the intestinal epithelium and the immune system as potential intermediaries between gut microbiota and ENS responses.     

The gut microbiota keeps enteric glial cells on the move; prospective roles of the gut epithelium and immune system

The enteric nervous system (ENS) coordinates the major functions of the gastrointestinal tract. Its development takes place within a constantly changing environment which, after birth, culminates in the establishment of a complex gut microbiota. How such changes affect ENS development and its subsequent function throughout life is an emerging field of study that holds great interest but which is inadequately explored thus far. In this addendum, we discuss our recent findings showing that a component of the ENS, the enteric glial cell network that resides in the gut lamina propria, develops after birth and parallels the evolution of the gut microbiota. Importantly, this network was found to be malleable throughout life by incorporating new cells that arrive from the area of the gut wall in a process of directional movement which was controlled by the lumen gut microbiota. Finally, we postulate on the roles of the intestinal epithelium and the immune system as potential intermediaries between gut microbiota and ENS responses.     

Relevant aspects of physiology in chronic pancreatitis.

Specific points of physiology which are relevant for the understanding and management of chronic pancreatitis are focussed on. First, the regulatory factors of exocrine pancreatic secretion are described, discussing the role of the cholinergic system and of the classical gut hormones cholecystokinin and secretin. The association of upper gastrointestinal dysfunctions with a disturbed exocrine pancreatic response is also dealt with. Lastly, these changes are related to clinical consequences such as maldigestion or malabsorption.     

Techniques used to characterize the gut microbiota: a guide for the clinician

The gut microbiota is a complex ecosystem that has a symbiotic relationship with its host. An association between the gut microbiota and disease was first postulated in the early 20(th) century. However, until the 1990s, knowledge of the gut microbiota was limited because bacteriological culture was the only technique available to characterize its composition. Only a fraction (estimated at <30%) of the gut microbiota has been cultured to date. Since the 1990s, advances in culture-independent techniques have spearheaded our knowledge of the complexity of this ecosystem. These techniques have elucidated the microbial diversity of the gut microbiota and have shown that alterations in the gut microbiota composition and function are associated with certain disease states, such as IBD and obesity. These new techniques are fast, facilitate high throughput, identify organisms that are uncultured to date and enable enumeration of organisms present in the gut microbiota. This Review discusses the techniques that can used to characterize the gut microbiota, when they can be applied to human studies and their relative advantages and limitations.     

肠道菌群与脓毒症相互关系的研究进展

脓毒症的发生发展与肠道菌群失调密切相关.肠道菌群失调可以通过肠黏膜屏障功能破坏、黏膜免疫功能破坏和细菌移位等环节诱导脓毒症的发生.同时脓毒症也可以加重肠道菌群失调,加重肠黏膜屏障功能破坏,导致机体多器官功能障碍.本文通过探讨肠道菌群和脓毒症之间的相互关系,为脓毒症临床干预提供思路.