Phenotype, intestinal morphology, and survival of homozygous and heterozygous endothelin B receptor--deficient (spotting lethal) rats.

BACKGROUND/PURPOSE: Spotting lethal (sl) rats, a model for Hirschsprung's disease, recently have been found to carry a deletion in the endothelin B (ET(B)) gene, causing functional lack of ET(B) receptors. The ET(B) receptor mediates, together with and in counterbalance to the ET(A) receptor, endothelin actions on vessels, cell proliferation, and migration. The authors investigated the effect of homozygosity (sI/sI) or heterozygosity (+/sl) on phenotype, intestinal morphology, and survival. METHODS: Weight, circumference, and serum albumin were measured. Histological tests of major organs and immunoperoxidase reaction for Peripherin, glial fibrillary acid protein (GFAP), and S-100 in small and large intestine were performed. Peripherin-immunostained sections of colon and jejunum were analyzed morphometrically. Screening for sepsis included search for enterocolitis, bacterial infection, endotoxin, and iNOS mRNA. RESULTS: Sl/sl rats died within 4 weeks of life, showing an early and a later death group. Serum albumin levels were decreased in sl/sl rats, whereas signs of sepsis were rare. Immunostaining uncovered alterations in nerve and glial cells in the whole gut of sl/sl rats, and to a subtle degree also in +/sl rats, which appear clinically normal. Morphometric quantification yielded statistically significant alterations in sl/sl rats only. No obvious abnormalities were found in other organs. CONCLUSIONS: Sl/sl rats die from malnutrition rather than sepsis, too early for ischemic complications to occur. Rats of the later death group are a suitable model for studying the ET8 receptor in vivo. Subtle abnormalities in the enteric nervous system of heterozygous rats underline the critical role of the "gene dose" for functional compensation.

Immunohistochemistry for intermediate filaments in the enteric nervous system of the porcine small intestine.

Antibodies against the cytoskeletal neurofilament protein 200 and gliafilament acidic protein were used for an immunohistochemical staining of nerve and glia cells in porcine small intestine. In sections as well as in whole mount preparations, the morphological and topographical features of the enteric nerve plexus could be demonstrated. The enteric glia cells are characterized by an abundance of immunoreactive GFAP, which allows a subsequent staining of the plexus. NFP 200 is immunohistochemically recognized only in a part of the neurons. This immunoreactive neuronal population can be identified morphologically as Typ II-neurons, which are defined as adendritic and pseudouniaxonal to multiaxonal. The immunostaining of intermediate filaments is an easy and reproducible means for studying the enteric nervous system and invaluable for the histopathological diagnosis of its morphological abnormalities.

[GFAP immunoreactivity in newly formed ileal mucosa in a serosal patch in dog colon]. / GFAP-Immunreaktivität in der Neomukosa des Ileums auf einem Serosa Patch des Colons beim Hund.

A Short bowel was induced in 8 beagle bitches by resecting 85% of the small intestine. Following resection, a tangential fixation was performed in antiperistaltic direction between the ileum and the proximal colon. A 15 cm segment of the remaining ileum was incised opposite to its mesenterial attachment and sewn onto the serosa of the neighboring segment of colon (Serosa patching). After 20 weeks of observation, segments of the ileum, the colon and the anastomosed intestinal segment were removed. The neomucosa covering the patch surface was investigated using immunohistochemical methods in order to demonstrate the presence of nerve fibers. The immunofluorescence reaction using anti-GFAP (glial fibrillary acidic protein) clearly demonstrated immunoreactivity in the formed neomucosa and in the underlying granulation tissue. The immunoreactive fibers were comparable with fibers demonstrated in the original mucosa. This finding is an indication that the neomucosa of a serosa patch may be functionally intact because the presence of nerves suggests that mucosal functions, e.g. resorption and secretion, are under nervous regulation.

Distribution of NADPH-diaphorase-positive neurons in the enteric nervous system of the human colon.

Recent investigations have demonstrated the colonization of NOS-immunoreactivity and NADPH-diaphorase staining in central and peripheral neurons. The current study investigates the presence and distribution of NADPH-diaphorase-stained nerve cells and fibres in whole-mount preparations of the enteric nervous system of the human colon. Numerous NADPH-diaphorase-stained nerve cell bodies were found in the plexus myentericus and in the plexus submucosus externus. In contrast, we found but very few NADPH-diaphorase-stained nerve cells in the plexus submucosus internus. The majority of the NADPH-diaphorase-stained nerve cells had morphological characteristics similar to those of the Dogiel type I neuron, i.e. possessing broad flat dendrites and one major axonal projection. NADPH-diaphorase-stained nerve fibres can be observed in all three ganglionic networks and in the aganglionic plexus of the circular muscle layer.

Immunohistochemical demonstration of nerves and nerve cells in human and porcine ureters.

There are divergent opinions about the origin of ureteral motility. It is either a myogenic or a neutral phenomenon. Furthermore, the existence of nerve cells in the ureter is also a controversial question. In the present study we applied immunohistochemical methods to human and porcine ureters in an attempt to clarify the mattern. As neuronal markers we used anti-PGP 9.5 and anti-NSE, and as a glial marker anti-S-100. In the whole mount preparations of pig ureter we observed two neuronal plexuses on both sides of the tunica muscularis. The inner plexus consisted of both nerve bundles and nerve cells, whereas the outer one did not contain any nerve cells. In the human ureter we found a ganglion with nerve cells beneath the tunica muscularis and the tunica adventitia.

Structural differences of the enteric nervous system in the cattle forestomach revealed by whole mount immunohistochemistry.

The specific motility patterns of the forestomach of ruminants, composed of three structurally distinct compartments (rumen, reticulum, omasum), require an elaborate intramural innervation. To demonstrate the complex structure of the enteric nervous system (ENS), whole mount preparations obtained from different sites of the bovine forestomach were submitted to immunohistochemical procedures in which neuronal (protein gene product 9.5, neurofilament 200) and glial (protein S-100, glial fibrillary acid protein) markers were applied. Immunohistochemistry performed on whole mounts allowed a detailed two-dimensional assessment of the architecture of the intramural nerve networks. Generally, the myenteric and submucosal plexus layers were composed of ganglia and interconnecting nerve fiber strands, whereas the mucosal plexus consisted of an aganglionated nerve network. However, the texture of the ENS showed considerable regional differences concerning the ganglionic size, shape and density and the arrangement of nerve fiber strands. The myenteric plexus of the ruminal wall, showing a low ganglionic density and wide polygonal meshes, contrasted with the nerve network within the ruminal pillar which consisted of ropeladder-like nerve fiber strands and parallel orientated ganglia. The highest ganglionic density was observed at the reticular groove, the most prominent ganglia were found within the omasal wall. Branches of the vagal nerve frequently ramified within the myenteric plexus layers. The submucosal plexus of the rumen was divided into an external and internal layer; the reticular submucosal plexus followed the cristae and cellulae reticuli, the omasal submucosal (sublaminar) plexus showed intra- and parafascicular ganglia apart from ganglia located at the junctions of the nerve network. The mucosal plexus of the rumen consisted of thin nerve fascicles ramifying between the ruminal papillae, and reticular mucosal nerve fibers passed throughout the base of the cellulae reticuli. The highly specialised nerve network of the intralaminar omasal plexus showed radial and transverse trajectories reflecting the spatial arrangement of the intralaminar musculature. The demonstrated structural complexity of the ENS reflects the functional complexity of the ruminant forestomach and indicates the relatively high degree of autonomy in coordinating the different motility patterns required for the processing of the ingesta.

Immunohistochemical visualization of the enteric nervous system using antibodies against protein gene product (PGP) 9.5.

Both the investigation of the enteric nervous system and the diagnosis of its pathological changes require reliable staining methods. In order to assess the potential of protein gene product (PGP) 9.5 as a marker for the enteric nervous system, we examined its immunoreaction in whole-mount preparations of the guinea pig and porcine small intestine, using a rabbit polyclonal antiserum. The immunohistochemical technique reveals the fundamental architectural features of the ganglionic and aganglionic plexuses. Furthermore, it enables a reproducible and differentiated visualization of the enteric nerve cells to be made, so that the various nerve cell types can be morphologically identified.

Distribution of nitric oxide synthase-immunoreactive neurons in the submucosal plexus of the porcine small intestine.

This study analyses the occurrence of NOS-immunoreactive neurons in the enteric nervous system of the porcine small intestine, and particularly their distribution pattern in the ganglia of the two submucosal plexuses, the external submucosal plexus and the internal submucosal plexus. Numerous NOS-immunoreactive nerve cell bodies were found in the external submucosal plexus, as well as in the myenteric plexus. In 1 cm2 of the surface of the submucosal whole-mount preparation, we counted 186 NOS-immunoreactive nerve cell bodies in the external submucosal plexus, which is about 27% of the total number of nerve cells in that plexus. As against this, we found only very few NOS-immunoreactive nerve cells in the internal submucosal plexus. In the external submucosal plexus, these cells are often located together, forming aggregates within the ganglia. NOS-immunoreactive nerve cells are of different sizes and shapes. Some of them have a multidendritic uniaxonal appearance. NOS-immunoreactive nerve fibres can be observed in all three ganglionic networks, surrounding NOS-immunoreactive as well as nonimmunoreactive nerve cell bodies and forming varicosities in close proximity to the nerve cell bodies.

Organization of the enteric nervous system in the human colon demonstrated by wholemount immunohistochemistry with special reference to the submucous plexus.

To demonstrate the normal topography and structure of the enteric nervous system (ENS) in the human colon, the colonic wall of patients (n = 10, mean age 66.3 years), who underwent abdominal surgery unrelated to intestinal motility disorders, was submitted to wholemount immunohistochemistry. The specimens were stretched out and separated into the tunica muscularis, the outer and inner portion of the tela submucosa and the tunica mucosa. Prior to the application of the neuronal marker Protein Gene Product (PGP) 9.5, the laminar preparations were pretreated with the maceration agent KOH. The plexus myentericus was composed of prominent ganglia and interconnecting nerve fiber strands (NFS) forming a polygonal network, which was denser in the descending than in the ascending colon. Nerve cells were observed within the ganglia as well as in primary, secondary and tertiary NFS. The latter ramified into the adjacent smooth muscle layers, which contained the aganglionated plexus muscularis longitudinalis and circularis. The submucous plexus comprised three nerve networks of different topography and architecture: the delicate plexus submucosus extremus consisted of parallel orientated NFS with isolated nerve cells and small ganglia and was located at the outermost border of the tela submucosa adjacent to the circular muscle layer. The plexus submucosus externus was closely associated with the plexus submucosus extremus and composed of larger ganglia and thicker NFS. The plexus submucosus internus was situated adjacent to the lamina muscularis mucosae and formed a network with denser meshes but smaller ganglia and NFS than the plexus submucosus externus. The NFS of the aganglionated plexus muscularis mucosae followed the course of the smooth muscle cells of the lamina muscularis mucosae. The honeycomb-like network of the plexus mucosus was located within the lamina propria mucosae and divided into a subglandular and a periglandular portion. Single and accumulated nerve cells were observed within the plexus mucosus as a regular feature. The findings confirm the complex structural organisation of the ENS encountered in larger mammals, in particular the subdivision of the submucous plexus into three different compartments. PGP 9.5-immunohistochemistry applied to wholemount preparations comprehensively visualized the architecture of the intramural nerve plexus in human colonic specimens. In addition to conventional cross-sections, this technique allows a subtle assessment and classification of structural alterations of the ENS in patients with colorectal motor disorders.

The morphology of xenotransplanted human breast carcinoma MX-1 growing in nude mice. A light and transmission electron microscopic study.

The present investigation is concerned with the morphological features of the human breast carcinoma MX-1, transplanted subcutaneously into nude mice. Three weeks after transplantation the tumor tissue is clearly distinct from the dermis. Solid tumor cell groups are separated incompletely by thin connective tissue septa, giving rise to a lobular appearance. The tumor cells are characterized by very irregularly formed nuclei with three or more nucleoli. The cytoplasm of these cells displays some lysosomes, the cisternae of the rough endoplasmic reticulum, mitochondria and a variable number of ribosomes. The Golgi fields are frequently observed, particularly near the nucleus. The cells are connected to each other by desmosomes, which also persist during mitotic activity. Ductular formations can occasionally be seen. The ultrastructure of the blood vessels discloses the morphological features necessary for the regulation of blood flow. Capillaries present a sinusoidal aspect with distended and narrow lumina. Interruptions of the endothelial wall, however, were not observed. This morphological appearance was found in all the MX-1 tumors investigated, reflecting the stable growth of this tumor cell line in nude mice.

Ultrastructural features of nerve fascicles and basal lamina abnormalities in Hirschsprung's disease.

Although the pathogenesis of Hirschsprung's disease (HD) is not completely resolved, both the absence of nerve cells and the hypertrophy of nerve fascicles within the aganglionic colonic segment have been attributed to an abnormal intestinal microenvironment. Studies on animal models for HD revealed an altered ultrastructure of ingrowing nerve fascicles and abnormalities of basal laminae (BL). Therefore, the purpose of this study was to examine the ultrastructure of hypertrophied nerve fascicles in human HD with special reference to structural abnormalities of BL. Colonic specimens were obtained from patients with HD (n = 10) and controls (n = 5) and processed for electron-microscopical examination. Hypertrophied nerve fascicles were characterized by a prominent perineural sheath surrounded by large amounts of collagen bundles, a collagen-filled endoneurium, vasa nervorum and abundant glial cells of extraenteric ultrastructure, which were arranged in mono- or oligoaxonal units and frequently displayed different stages of myelination. As these ultrastructural characteristics resembled typical features of extrinsic nerves and were similar to those observed in subserosal nerves, the prominent intramural nerve fascicles were considered to be of extraenteric origin. Most likely their overabundance contributes to the functional obstruction of the terminal colon. Morphological abnormalities of BL encountered in the aganglionic colonic segment consisted of an extensive multilamination of BL surrounding glial processes and an irregular thickening of BL surrounding perineurocytes and smooth muscle cells of the muscularis mucosae. Similar alterations in BL have also been described in inherited peripheral and diabetic autonomic neuropathies and attributed to reactivated schwann cells. Thus, the overproduction of BL material within the hypertrophied nerve fascicles in HD may reflect an increased activity of proliferating glial cells. Since the smooth muscle cells of the muscularis mucosae showed abnormalities of BL similar to those observed in murine models for HD, it is suggestive that also in human HD the aganglionic colon is affected by a disturbed intestinal micro-environment impairing the neuronal colonisation and promoting the ingrowth of extrinsic nerves. The ultrastructurally observed alterations in BL of both neuronal and non-neuronal cells, as well as the increased amount of perineural and endoneural collagen provide further evidence that extracellular matrix components are abnormally distributed and overproduced within the bowel wall of patients affected by HD.

Immunohistochemistry of markers of the enteric nervous system in whole-mount preparations of the human colon.

In this study we tested the immunohistochemical reactions of various markers for the enteric nervous system in whole-mount preparations of the human colon. For that purpose we used polyclonal antibodies against the neuronal markers--protein gene product 9.5 (PGP), neuron-specific enolase (NSE), neurofilament protein 200 (NFP), microtubule-associated proteins (MAPs); and the glial markers--S-100 protein and glial fibrillary acidic protein (GFAP) for the immunoperoxidase reaction. Whole-mount preparations are more suitable for histopathological evaluation and interpretation than sections, because the enteric nervous system consists of three-dimensional plexuses lying within the layers of the intestinal wall. Sections show only a part of the plexuses, neurons and glial cells. On the other hand, whole-mount preparations reveal the morphology of the plexuses as a whole. Among the neuronal and glial markers used, S-100 protein, the neurofilament protein, and the protein gene product 9.5 (PGP) produced the best results. Furthermore, this developing method provides new possibilities for the histopathological analysis of defects in the enteric nervous system, such as neuronal intestinal dysplasia (NID).

Morphologic alterations of the enteric nervous system and deficiency of non-adrenergic non-cholinergic inhibitory innervation in neonatal necrotizing enterocolitis.

Although damage to intramural nervous tissue should be expected in neonatal necrotizing enterocolitis (NNEC), as the pathology of NNEC is defined by substantial destruction of the bowel wall, only a few studies have considered its implication. Thus, the aim of the study has been to examine morphological alterations of the enteric nervous system (ENS) in intestinal segments affected by NNEC. Immunohistochemical methods allowed the demonstration of both neuronal and glial elements and the assessment of an altered localization of non-adrenergic non-cholinergic (NANC) inhibitory mediators within the intramural plexuses. Intestinal segments from patients with NNEC (n = 8) and control subjects (n = 3) were obtained and submitted to immunohistochemical examination incubating with antibodies against protein gene product (PGP) 9.5, protein S-100, vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS). The most severe damage of nervous tissue was found within the plexus mucosus and plexus submucosus internus. The ganglionated plexuses showed a loss ot both glial and nerve cells with various stages of cell deterioration and the formation of central lesions within the myenteric ganglia. The observed neuropathologic changes correspond to the group of acquired segmental hypoganglionosis. Specimens from patients with NNEC were also characterized by an absence of immunoreactive VIP and NOS in the plexus submucosus and within the circular muscle layer. The deficiency in NANC inhibitory innervation may contribute to the formation of functional obstructions following acute NNEC. Furthermore, it is likely that the neuropathological lesions induced in early stages of NNEC may result in dysfunctional intestinal motility facilitating intraluminal bacterial overgrowth and translocation, and therefore, possibly promote the self-perpetuating pathophysiologic cycle culminating in progressive NNEC. As an additional finding, two patients with NNEC showed typical features of intestinal neuronal dysplasia (IND). The association of NNEC and IND is reviewed in the literature and possible causalties are discussed.

Histopathological features of neuronal intestinal dysplasia of the plexus submucosus in whole mounts revealed by immunohistochemistry for PGP 9.5.

Neuronal intestinal dysplasia (NID) is wellknown, but its definition is a topic of debate. The histopathological diagnosis of NID is based on traditional enzyme-histochemical methods such as the acetylcholinesterase and dehydrogenase reaction on native cryosections. In this study, we have investigated the enteric nervous system in whole mount preparations of resected intestinal segments affected by NID of the plexus submucosus (type B). The plexuses of the tunica mucosa and tunica submucosa were visualized by immunohistochemical methods using a polyclonal antibody to protein gene produce 9.5 (PGP 9.5). PGP 9.5 is a novel general cytoplasmatic marker specific for the nervous system. The morphology of the plexuses is revealed in full, making possible changes easily discernible. Known pathological findings of the NID can be identified and judged more precisely with this method. Numerous enlarged nerve trunks run within the tunica submucosa and tunica mucosa. Hyperplastic ganglia with an unusually high nerve cell number in the tunica submucosa can be demonstrated as well as heterotopic nerve cells in the tunica mucosa.

Molecular genetics of colorectal motility disorders.

In the last years, several genes have been identified which are involved in the development and differentiation of the enteric nervous system (ENS). Among the congenital intestinal innervation disorders described (aganglionosis, hypoganglionosis, heterotopic ganglia, intestinal neuronal dysplasia), up to now Hirschsprung's disease (HSCR) has been linked to mutational defects in these genes. GDNF and its co-receptor RET are the genes with the most mitogene potency on precursor cells of the ENS. The endothelin system (EDNRB/EDN3) also plays a key role in the development of the ENS by preventing its premature differentiation. Our own studies could show that, whereas a homozygous mutation of EDNRB causes long-segment HSCR, a heterozygous EDNRB deficiency leads to alterations of the ENS resembling the histopathology observed in intestinal neuronal dysplasia. Modern molecular genetic technologies combined with a subtle phenotypic assessment of the ENS will allow investigators to identify other genes within the complex signalling cascade required for the formation of the ENS. The recognition that intestinal innervation disorders are, at least in part, a multigenetic disease should provide support for consequent genetic screening in these patients.

Mitochondrial myopathy (complex I deficiency) associated with chronic intestinal pseudo-obstruction.

We report a patient presenting with severe muscular impairment and chronic intestinal pseudo-obstruction (CIP) at the age of eight months. Due to the aggravated symptoms, assisted ventilation, an ileostomy and total parenteral nutrition were required. Later on, the patient developed a locked-in syndrome (Leigh's subacute necrotising encephalomyelopathy) and finally died due to recurrent pneumonia and chronic renal failure. The assessment of muscle biopsies revealed a moderate single-fibre type II atrophy, a variation of muscle fibre calibre with focal fatty degeneration and a decreased reactivity of cytochrome-c oxidase. Although ragged red fibres had not been found, mitochondrial enzyme activities were markedly decreased with the lowest residual activity detected for NADH:Q1 oxidoreductase and NADH:O2 oxidoreductase (complex I deficiency), thereby confirming the diagnosis of mitochondrial myopathy. A molecular genetic analysis could not identify known mutations of mitochondrial DNA. Gastrointestinal full-thickness biopsies revealed myenteric hypoganglionosis of the colon and stomach and hyperplasia of the submucosal plexus of the ileum. Some of the intestinal smooth muscle cells displayed bulbous protrusions filled with lateralised mitochondria. Mitochondrial myopathies are known to be associated with a variety of clinical syndromes including CIP. However, in contrast to previous reports in which CIP has been attributed to visceral intestinal myopathies, the present case is characterised by neuronal intestinal malformations. Therefore, a mitochondrial myopathy associated with CIP requires a subtle assessment of both the intestinal smooth muscle and the enteric nervous system to identify the underlying pathology.

[The enteric nervous system and interstitial cells of Cajal. Changes in chronic constipation in adults]. / Enterisches Nervensystem und interstitielle Cajal-Zellen. Veränderungen bei chronischer Obstipation im Erwachsenenalter.

Intestinal innervation disorders are part of the broad etiological spectrum of chronic constipation and need to be specifically addressed in differential diagnosis. The enteric nervous system constitutes the largest peripheral nervous system of its own ("brain in the gut"), and is involved in the mediation of intestinal motility. Morphologically different nerve cell types aggregate into intramural plexus layers and release a multitude of neurotransmitters. Malformations or lesions of the enteric nervous system may lead to a severely prolonged intestinal transit time resulting in chronic constipation resistant to conservative treatment. In contrast to the early manifestation of aganglionosis, non-aganglionic or acquired alterations to the intramural nerve plexus often remain unrecognised up to adulthood. Histopathological diagnosis is carried out by enzyme or immunohistochemical staining, either on sections or whole mount preparations, allowing an optimal visualization of the nerve plexus architecture. To diagnose hypoganglionosis, enteric ganglionitis or alterations in interstitial cells of Cajal, full-thickness biopsies are required. Interstitial cells of Cajal contribute significantly to the mediation of intestinal motility by generating "slow wave" activity. In adult patients with slow-transit constipation and megacolon, the intramuscular networks of the interstitial cells of Cajal show a significantly reduced density.

[Anorectal manometry]. / Empfehlungen zur Anorektalen Manometrie im Erwachsenenalter.

This document contains the guidelines of the German Societies of Neurogastroenterology and Motility, Gastroenterology (committee for proctology), Abdominal Surgery (coloproctology working group), and Coloproctology for anorectal manometry in adults. Recommendations are given about technical notes, study preparation (equipment; patient), technique for performing manometry and data analysis, reproducibility, and indications. Minimum standards for anorectal manometry are measurement of resting and squeeze pressure, testing of rectoanal inhibitory reflex, determination of rectal sensation (first perception and urge), and calculation of rectal compliance. Anorectal manometry is indicated in patients with fecal incontinence and constipation in the context of a structured programme.

[Probiotic drug therapy with E. coli strain Nissle 1917 (EcN): results of a prospective study of the records of 3,807 patients]. / Probiotische Arzneimitteltherapie mit E. coli Stamm Nissle 1917 (EcN): Ergebnisse einer prospektiven Datenerhebung mit 3,807 Patienten.

INTRODUCTION: Living microorganisms that enter the gut in an active state and exert a positive influence on the host are called probiotics. Numerous experimental and clinical studies were performed recently and confirm both the efficacy and modes of action of probiotic drugs. PATIENTS AND METHODS: In a post-marketing-surveillance study with the probiotic Escherichia Coli strain Nissle 1917 (EcN) data on the range of indications as well as on efficacy and tolerance were gathered prospectively in 446 centres. The intended treatment duration was limited to a maximum of 12 weeks. RESULTS: EcN was used in 3,807 patients with more than 20 different indications, n = 3,511 of whom had gastrointestinal complaints: Among others, 1,067 patients presented with chronically recurring (n = 728) or protracted diarrhoea (n = 339), 415 with inflammatory bowel disease, 679 with irritable bowel syndrome, and 253 with chronic constipation. The overall efficacy was assessed as good to very good by an average of 81.4 % of the therapists. The stool frequency and consistency as well as the symptoms of meteorism and abdominal pain were improved in very many patients. Suspected cases of side effects were documented in only 2.8 % of the patients. CONCLUSION: EcN is frequently used in practice for the treatment of various, mostly gastrointestinal, complaints and is well tolerated.

[Probiotics as therapeutic agents in irritable bowel syndrome]. / Probiotika in der Therapie des Reizdarmsyndroms.

Probiotics are defined as living micro-organisms which, when administered in large amounts, confer a health benefit on the host. The use of probiotics in the therapy of infectious bowel diseases as well as maintaining remission of ulcerative colitis and in pouchitis is evidence-based. Also, in several studies proof could be supplied that specific probiotics relieve the symptoms and the course of irritable bowel syndrome. Some trials showed a significant improvement of irritable bowel syndrome-related constipation via Lactobacillus casei Shirota and E. coli Nissle 1917. Lactobacillus plantarum has been proven effective in reducing pain and abdominal bloating. However, in most of the studies rather small numbers of patients were examined. Furthermore, these studies do not always closely follow scientific standards (randomised, double-blind, placebo-controlled). Therefore, confirmatory studies are necessary to examine the effect of probiotics in irritable bowel syndrome.