Pathophysiological responses from human gut microbiome

The human gastrointestinal tract harbors a vast collection of symbiotic microorganisms-collectively termed as "gut microbiome". This microbiota has important effect in immune system and other host activities. Recent studies have suggested that alterations of the normal gut microbiota are associated with various human diseases and psychological disorders. The underlying cause, once proven, may provide novel insights into the importance of gut flora in human health. In this review, we give an attempt to describe how the alteration in the microbial community causes the development of certain widespread pathophysiological disorders; focusing on inflammatory bowel disease, colorectal cancer, obesity and autism. Proper knowledge about the hostmicrobiota interaction and linkage could be essential for the development of future personalized strategies of therapeutics.     

Glutamine and the gastrointestinal tract

The amino acid glutamine has become one of the most intensively studied nutrients in the field of nutrition and metabolic support. A variety of studies in cell culture systems, animal models of gut mucosal atrophy, injury/repair and adaptation and a limited number of clinical trials demonstrate trophic and cytoprotective effects of glutamine in small bowel and colonic mucosal cells. Although the routine clinical use of glutamine-enriched parenteral and enteral nutrient solutions remains controversial, available data demonstrate both the safety and metabolic and clinical efficacy of glutamine treatment in selected patient groups. Basic investigations are elucidating underlying mechanisms of glutamine action in intestinal cells. These will inform preclinical and clinical investigations designed to determine glutamine efficacy in selected gastrointestinal disorders. Emerging clinical trials will further define the utility of adjunctive glutamine supplementation as a component of specialized nutrition support in gastrointestinal disease.     

Pegvisomant: a new treatment modality for acromegaly

Acromegaly, a multisystemic disease resulting from excessive growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels in adults, is associated with a two-to-threefold increase in mortality. The available treatment options (surgery, radiotherapy and medical treatment with somatostatin analogues or dopamine agonists) fail to achieve the currently accepted goals of therapy in a substantial number of patients. Pegvisomant, a newly developed GH receptor antagonist, represents a novel treatment modality for this disease. It binds with the GH receptor and induces internalization, but blocks receptor signaling events, thereby reducing IGF-I production. The two main published studies suggest that it is the most potent medical therapy with greater specificity, without being dependent on the tumour characteristics. However, apart from its high cost and the dilemmas raised concerning the appropriateness of using serum IGF-I concentrations as a marker of disease activity, it may also occasionally be associated with elevations in liver enzyme levels. Further studies are required to confirm its high success rates as well as to investigate the possibility of inducing an increase in the pituitary tumour size. Currently, pegvisomant is a second line treatment for acromegaly with an adjuvant role and possibly of greater value in cases of resistance to other therapeutic options.     

The Potential Role of Probiotics in Cancer Prevention and Treatment

The human gut microbiota has a significant effect on many aspects of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including inflammatory bowel disease, obesity, asthma, psychiatric illnesses, and cancers. As a kind of functional foods, probiotics have been shown to play a protective role against cancer development in animal models. Clinical application of probiotics indicated that some probiotic strains could diminish the incidence of postoperative inflammation in cancer patients. Chemotherapy or radiotherapy-related diarrhea was relieved in patients who were administered oral probiotics. The present review summarizes the up-to-date studies on probiotic effects and the underlying mechanisms related to cancer. At present, it is commonly accepted that most commercial probiotic products are generally safe and can improve the health of the host. By modulating intestinal microbiota and immune response, some strains of probiotics can be used as an adjuvant for cancer prevention or/and treatment.     

Probiotics and intestinal health effects: a clinical perspective

Probiotics are viable non-pathogenic micro-organisms which, when ingested, exert a positive influence on host health or physiology. We have critically analysed the evidence for the efficacy of specific probiotic strains in human gastrointestinal diseases. The best evidence can be obtained with randomised controlled trials which avoid bias. Good evidence has been obtained with several strains in the prevention or treatment of antibiotic-associated disorders, in the treatment (and to a lesser extent prevention) of gastroenteritis and acute diarrhoea and in the alleviation of lactose intolerance. We also analysed the recent randomised controlled trials performed in patients with Clostridium difficile or Helicobacter pylori, inflammatory bowel disease, irritable bowel syndrome, non-ulcer dyspepsia and colon cancer.     

Mechanisms by which nutritional disorders cause reduced bone mass in adults

Nutritional disorders that cause bone loss in adults include disordered eating behaviors (female athlete triad and anorexia nervosa), gastrointestinal diseases (celiac sprue, inflammatory bowel disease, and other malabsorption syndromes), alcoholism, and hypervitaminosis A. These disorders exert their effects on bone through a number of mechanisms, including estrogen deficiency. Deficiencies of anabolic hormones may also be important, including insulin-like growth factor I (IGF-I), a nutritionally regulated bone trophic factor. In addition, low weight itself is a risk factor for bone loss and decreased bone formation. Reduced calcium and vitamin D availability, with resultant secondary hyperparathyroidism, is another important mechanism of bone loss in nutritional disorders. This review discusses nutritional causes of reduced bone mass in adults and how nutritional disorders exert deleterious effects on the skeleton.     

Anti- and proinflammatory cytokines in the pathogenesis of tissue damage in Crohn's disease

Crohn's disease is a chronic inflammatory bowel disease of unknown origin. The understanding of the pathogenesis of inflammatory bowel diseases has been greatly advanced by manipulations of the immune system in mice using targeted disruptions of genes that encode specific anti- and proinflammatory cytokines, as well as T-cell subsets. The outcome of these experiments has implicated CD4+ lymphocytes and certain proinflammatory cytokines (tumour necrosis factor-alpha, interleukin-12) as playing a central role in the pathogenesis of mucosal inflammation in Crohn's disease. The present review focuses on these recent important immunological observations, and discusses several newly developed therapeutic strategies that are based either on blocking proinflammatory cytokines or on the administration of anti-inflammatory cytokines.     

Role of Vitamin D in Celiac Disease and Inflammatory Bowel Diseases

Vitamin D (VD) is a pro-hormone that has long been known as a key regulator of calcium homeostasis and bone health in both children and adults. In recent years, studies have shown that VD may exert many extra-skeletal functions, mainly through a relevant modulation of the innate and adaptive immune system. This has suggested that VD could play a fundamental role in conditioning development, clinical course, and treatment of several autoimmune disorders, including celiac disease (CD) and inflammatory bowel diseases (IBDs). The main aim of this review is to evaluate the relationships between VD, CD, and IBDs. Literature analysis showed a potential impact of VD on CD and IBDs can be reasonably assumed based on the well-documented in vitro and in vivo VD activities on the gastrointestinal tract and the immune system. The evidence that VD can preserve intestinal mucosa from chemical and immunological damage and that VD modulation of the immune system functions can contrast the mechanisms that lead to the intestinal modifications characteristic of gastrointestinal autoimmune diseases has suggested that VD could play a role in controlling both the development and the course of CD and IBDs. Administration of VD in already diagnosed CD and IBD cases has not always significantly modified disease course. However, despite these relevant problems, most of the experts recommend monitoring of VD levels in patients with CD and IBDs and administration of supplements in patients with hypovitaminosis.     

Mechanistic Insight of Probiotics Derived Anticancer Pharmaceuticals: A Road Forward for Cancer Therapeutics

Probiotics are living organisms that confer health benefits when administered in adequate amounts. Probiotics are continuously being explored for their different health beneficiary activities. Anticancer activity is one of the most important benefits both from a preventive and therapeutic point of view. Though not many studies have been conducted to date in this area, a number suggest using laboratory animal models and different cell lines that there may be a mechanistic basis for the anticancer effects of probiotics and require more scientific justification and clinical trials. Most studies of probiotics are conducted for colon cancer associated with inflammatory bowel disease. Studies are also being extended to other types of cancer in different cell lines. This review summarizes studied probiotics considered for treatment of colon cancer and some other cancers (in cancer cell lines) and also proposed mechanism how probiotics are inhibiting cancer growth along with some challenges and future perspectives.     

Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders

Colostrum is the specific first diet of mammalian neonates and is rich in immunoglobulins, antimicrobial peptides, and growth factors. In this article we review some of these constituents of human and bovine colostrum in comparison with those of mature milk. Recent studies suggest that colostral fractions, or individual peptides present in colostrum, might be useful for the treatment of a wide variety of gastrointestinal conditions, including inflammatory bowel disease, nonsteroidal antiinflammatory drug-induced gut injury, and chemotherapy-induced mucositis. We therefore discuss the therapeutic possibilities of using whole colostrum, or individual peptides present in colostrum, for the treatment of various gastrointestinal diseases and the relative merits of the 2 approaches.     

Yogurt and gut function

In recent years, numerous studies have been published on the health effects of yogurt and the bacterial cultures used in the production of yogurt. In the United States, these lactic acid-producing bacteria (LAB) include Lactobacillus and Streptococcus species. The benefits of yogurt and LAB on gastrointestinal health have been investigated in animal models and, occasionally, in human subjects. Some studies using yogurt, individual LAB species, or both showed promising health benefits for certain gastrointestinal conditions, including lactose intolerance, constipation, diarrheal diseases, colon cancer, inflammatory bowel disease, Helicobacter pylori infection, and allergies. Patients with any of these conditions could possibly benefit from the consumption of yogurt. The benefits of yogurt consumption to gastrointestinal function are most likely due to effects mediated through the gut microflora, bowel transit, and enhancement of gastrointestinal innate and adaptive immune responses. Although substantial evidence currently exists to support a beneficial effect of yogurt consumption on gastrointestinal health, there is inconsistency in reported results, which may be due to differences in the strains of LAB used, in routes of administration, or in investigational procedures or to the lack of objective definition of "gut health." Further well-designed, controlled human studies of adequate duration are needed to confirm or extend these findings.     

An overview of tube feeding: from ancient times to the future.

The history of enteral feeding goes back about 3,500 years to the ancient Greeks and Egyptians, who infused nutrient solutions into the rectum to treat various bowel disorders. Over the centuries, experimentation and research have contributed to a greater understanding of nutrient requirements; methods to more accurately access the gastrointestinal tract; development of new materials to use in equipment, tubes, and containers; and the digestion, absorption, and use of macro- and micronutrients. It is notable that while advances were made in one area, progress was being made in another. For example, while enteral access and feeding techniques were being developed, essential amino acids were identified. When new information came together, rapid changes opened up the applications for enteral feeding in new directions, sometimes in unexpected ways such as diets designed for the space program, leading to the use of elemental diets as a therapeutic modality.     

High-dose chemotherapy with stem cell support for solid tumors in adults]

High-dose chemotherapy for advanced solid malignancies has been the subject of many clinical studies. The replacement of autologous bone marrow transplantation by peripheral blood haematopoietic progenitor cell transplantation and other advances in supportive care have led to a considerable reduction of therapy-related mortality and morbidity. In certain rare disorders, such as germ cell tumours or pediatric sarcomas in adults, high-dose therapy is currently considered the therapeutic standard. It is likely that a subgroup of patients with high-risk or disseminated breast cancer can also benefit in terms of survival from this treatment modality, but final proof from randomized studies remains to be generated. On theoretical grounds, high-dose chemotherapy could also be effective in small cell lung cancer and ovarian cancer, and randomized studies to answer this question are in progress. Many investigators concur that high-dose chemotherapy often leads to dramatic cytoreduction in solid tumours, but only rarely achieves cure. Novel therapeutic modalities are required to control the residual microscopic disease.     

Prebiotics and probiotics: their role in the management of gastrointestinal disorders in adults

For decades, if not centuries, a variety of products with what would now be regarded as prebiotic and probiotic properties have been consumed by the general public and advocated for their benefits on health and, in particular, gastrointestinal well-being. More recently, medical science has taken a great interest in the population of micro-organisms, the gut microbiota that normally populates the human gut, and the range of important functions carried out by the microbiota in health is being progressively defined. As a corollary, the list of disorders and diseases that may result from disruption of the normal microbiota and/or its interaction with the host continues to grow. A scientific basis for the use of probiotics and prebiotics is, therefore, beginning to emerge. Unfortunately, although progress has been made, the clinical evidence to support the use of these preparations lags behind. Nevertheless, a number of human disease states may benefit from the use of probiotics, most notably, diarrheal illnesses, some inflammatory bowel diseases, certain infectious disorders, and irritable bowel syndrome. Prebiotics promote the growth of "good" bacteria, and although a variety of health benefits have been attributed to their use, prebiotics have been subjected to few large-scale clinical trials.     

Endoscopic, radiographic, and clinical response to prolonged bowel rest and home parenteral nutrition in Crohn's disease

Total parenteral nutrition is widely used as a therapeutic measure in patients with severe, active Crohn's disease unresponsive to conventional medical management. We have reviewed our experience with 10 patients with nonfistulous Crohn's disease treated by home parenteral nutrition (HPN) and bowel rest (nothing-by-mouth) assessing the nutritional, radiologic, endoscopic, and clinical responses. After a mean of 4.1 months of treatment, all patients had a marked improvement in nutritional status and resolution of gastrointestinal symptoms; 90% reduced their corticosteroid dose. Eight of nine patients had endoscopic and/or radiographic evidence of mucosal healing. Although 60% of patients were able to avoid surgery and tolerate refeeding, all six patients continue to require steroids to control symptoms. Our study suggests that HPN and bowel rest is a useful therapeutic approach to selected patients with active Crohn's disease, which permits a reduction in corticosteroid dosage and partial healing of mucosal lesions in most. Further studies are required to determine which patients should receive HPN and its optimal duration.     

The pathogenetic significance of intestinal Candida colonization--a systematic review from an interdisciplinary and environmental medical point of view

The etiological significance of intestinal Candida colonization continues to be controversial. This is a systematic review to determine the pathogenetic significance of intestinal Candida colonization. The search was essentially performed from 1990 to 12/7/2000 in Medline and the Cochrane-Library. The data source was restricted to articles in English and German. Selection criteria covered the topics "Epidemiology", "Infectious Diseases", "Candida-Syndrome" and "Therapy" and were essentially confined to in-vivo examination of immunocompetent adults. Two reviewers extracted independently data using predefined criteria. In total, 96 citations that proved suitable for use in the systematic review were found. Depending on the localization in the gastrointestinal tract, the recovery technique employed, and transport times, Candida colonization is frequently detected in healthy, immunocompetent adults (prevalence: 4-88%). None of the studies available so far furnish any evidence that nutritional factors, food additives, pollutants, anti-ovulants, other types of medication or diabetes mellitus might be predisposing factors for intestinal Candida colonization. However, therapeutic studies point to the possibility of Candida playing a role in antibiotic-associated diarrhea. On the other hand, antibiotics seem to favor bacterial dysbiosis, and this, like the direct side effects of drugs, offers a more plausible explanation for diarrhea or gastrointestinal symptoms. The role of intestinal colonization by Candida in Candida-associated vulvovaginitis and IgE-mediated disorders remains contradictory. Nevertheless, neither epidemiological nor therapeutic studies provide evidence for the existence of the so-called "Candida-syndrome" or "Candida-hypersensitivity-syndrome". At present, there are no proven treatment indications for antifungal "bowel decontamination".     

The role of probiotics in gastrointestinal disease.

Patients with intestinal failure often have diarrhea for a variety of reasons. Treatment of diarrhea has centered on the use of antidiarrheal medications and antibiotic therapy. Recently, there has been interest in the oral administration of probiotics for these patients with small bowel bacterial overgrowth, inflammatory bowel disease, and radiation enteritis. This paper reviews the studies that have used probiotics to treat patients with short bowel syndrome and gastrointestinal disorders. Additionally, some of the specific issues regarding probiotics are addressed.     

The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.     

The gastroenterology service: a survey of general practitioners' requirements.

A postal questionnaire was sent to 634 Leicestershire general practitioners about the service they wanted from their local gastrointestinal unit. Their views were specifically sought in relation to the care of chronic gastrointestinal disorders such as coeliac disease and inflammatory bowel disease. This initial survey was 'testing the water' before addressing GP needs in all areas of gastroenterology including, management issues in peptic ulcer disease and hiatus hernia. The design of the questionnaire was simple with only 12 'yes' or 'no' stems. The response rate to one mailing of the questionnaire was 41% with the rate for each question ranging from 83% (on whether a telephone hot-line would be useful) to 99% (on the value of treatment protocols). There was a poor response rate to some individual stems, with rates of less than 10%, because most GPs only answered 'yes' to the stem they were interested in without answering 'no' to other parts. Most GPs wanted a regular news bulletin on the management of both inflammatory bowel disease and coeliac disease as well as detailed protocols on their treatment. Sixty per cent of respondents wanted a telephone hot line to senior gastroenterologists, with direct dialing to provide immediate advice. Eighty per cent of GPs want shared care with hospital consultants of such patients. A similar proportion thought that this decision should be made jointly by patients and their doctors. There is a clear desire by GPs for a more specialist education in line with the current trend of extending their role. GPs in Leicestershire would value a more active role in the management of patients with chronic intestinal diseases and it is likely that such views are widespread in Great Britain.     

Colostrum Therapy for Human Gastrointestinal Health and Disease

There is increasing awareness that a broad range of gastrointestinal diseases, and some systemic diseases, are characterized by failure of the mucosal barrier. Bovine colostrum is a complex biological fluid replete with growth factors, nutrients, hormones, and paracrine factors which have a range of properties likely to contribute to mucosal healing in a wide range of infective, inflammatory, and injury conditions. In this review, we describe the anatomy and physiology of the intestinal barrier and how it may fail. We survey selected diseases in which disordered barrier function contributes to disease pathogenesis or progression, and review the evidence for or against efficacy of bovine colostrum in management. These disorders include enteropathy due to non-steroidal anti-inflammatory drugs (NSAIDs), inflammatory bowel disease (IBD), necrotizing enterocolitis, infectious diarrhea, intestinal failure, and damage due to cancer therapy. In animal models, bovine colostrum benefits NSAID enteropathy, IBD, and intestinal failure. In human trials, there is substantial evidence of efficacy of bovine colostrum in inflammatory bowel disease and in infectious diarrhea. Given the robust scientific rationale for using bovine colostrum as a promoter of mucosal healing, further work is needed to define its role in therapy.