Definitive diagnosis is made by suction biopsy of the distally narrowed segment. A histologic examination of the tissue would show a lack of ganglionic nerve cells. Diagnostic techniques involve anorectal manometry, barium enema, and rectal biopsy.

The suction rectal biopsy is considered the current international gold standard in the diagnosis of Hirschsprung's disease.

Radiologic findings may also assist with diagnosis. Cineanography (fluoroscopy of contrast medium passing anorectal region) assists in determining the level of the affected intestines.

Diagnosis is achieved mainly by plain and contrasted radiographical and ultrasound imaging. Colonic marker transit studies are useful to distinguish colonic inertia from functional outlet obstruction causes. In this test, the patient swallows a water-soluble bolus of radio-opaque contrast and films are obtained 1, 3 and 5 days later. Patients with colonic inertia show the marker spread throughout the large intestines, while patients with outlet obstruction exhibit slow accumulations of markers in some places. A colonoscopy can also be used to rule out mechanical obstructive causes. Anorectal manometry may help to differentiate acquired from congenital forms. Rectal biopsy is recommended to make a final diagnosis of Hirschsprung disease.

Conservative treatment involves the long term use of laxatives and enemas, and has limited success. Dietary changes in order to control the disease are ineffective and high fiber diets often worsen the symptoms in children. As a last resort, surgical treatment (internal sphincter myectomy or colon resection) is used. In extreme cases, the only effective cure is a complete transplant of the affected parts.

Treatment of Hirschsprung's disease consists of surgical removal (resection) of the abnormal section of the colon, followed by reanastomosis.

The appearance of microvillous inclusion disease on light microscopy is similar to celiac sprue; however, it usually lacks the intraepithelial lymphocytic infiltration characteristic of celiac sprue and stains positive for carcinoembryonic antigen (CEA).

The definitive diagnosis is dependent on electron microscopy.

The differential diagnosis of chronic and intractable diarrhea is:

- Intestinal epithelial dysplasia

- Syndromatic diarrhea

- Immunoinflammatory enteropathy

A complete history and physical examination can be suggestive, especially if a palpable mass in the right lower quadrant of the abdomen is present (though this can be present in the absence of DIOS). Ultrasound and computed tomography (CT) imaging of the abdomen can confirm the diagnosis by demonstrating dilated loops of intestine with material in the intestinal lumen with bubbles. Air-fluid levels may be seen in those affected by DIOS.

There is a diagnostic test for AIE that looks for an antibody against the enterocyte. The diagnostic test contains the Western Blot which can identify the antibody IgG or IgA and with the immunohistochemistry can localize these antibodies. Endoscopy with biopsies of the colon, small colon, stomach, and other locations may be helpful in diagnosing. This test is done to look at the stomach and small intestines and to see what cells are infiltrating the digestive tract. There are also documented cases of autoimmune enteropathy where the auto-antibodies were undetectable and the diagnosis was made on the basis of clinical presentation and response to treatment.

There is no cure for short bowel syndrome except transplant. In newborn infants, the 4-year survival rate on parenteral nutrition is approximately 70%. In newborn infants with less than 10% of expected intestinal length, 5 year survival is approximately 20%. Some studies suggest that much of the mortality is due to a complication of the total parenteral nutrition (TPN), especially chronic liver disease. Much hope is vested in Omegaven, a type of lipid TPN feed, in which recent case reports suggest the risk of liver disease is much lower.

Although promising, small intestine transplant has a mixed success rate, with postoperative mortality rate of up to 30%. One-year and 4-year survival rate are 90% and 60%, respectively.

Additional diagnoses which may present with similar symptoms to DIOS include severe constipation, appendicitis, and intussusception.

It can be grouped into NID A and NID B, with the "A" form affecting the sympathetic innervation, and the "B" version affecting the parasympathetic innervation.

In 2002 Martucciello G et al. published the first analysis of associated anomalies in IND population is an important clinical approach to investigate possible pathogenetic correlations. Two recessive syndromes were identified (3 families). The first was characterized by NID B, intestinal malrotation, and congenital short bowel, the second by NID B, short stature, mental retardation, and facial dysmorphism. In this study, gastrointestinal anomalies accounted for 67.4% of all associated disorders. These data suggest a strong correlation between IND and intestinal development.

Possible treatments include:

- In stable cases, use of laxatives and bulking agents, as well as modifications in diet and stool habits are effective.

- Corticosteroids and other anti-inflammatory medication is used in toxic megacolon.

- Antibiotics are used for bacterial infections such as oral vancomycin for "Clostridium difficile"

- Disimpaction of feces and decompression using anorectal and nasogastric tubes.

- When megacolon worsens and the conservative measures fail to restore transit, surgery may be necessary.

- Bethanechol can also be used to treat megacolon by means of its direct cholinergic action and its stimulation of muscarinic receptors which bring about a parasympathetic like effect.

There are several surgical approaches to treat megacolon, such as a colectomy (removal of the entire colon) with ileorectal anastomosis (ligation of the remaining ileum and rectum segments), or a total proctocolectomy (removal of colon, sigmoid and rectum) followed by ileostomy or followed by ileoanal anastomosis.

Diagnosis is very difficult, and usually one of exclusion. SMA syndrome is thus considered only after patients have undergone an extensive evaluation of their gastrointestinal tract including upper endoscopy, and evaluation for various malabsorptive, ulcerative and inflammatory instestinal conditions with a higher diagnostic frequency. Diagnosis may follow x-ray examination revealing duodenal dilation followed by abrupt constriction proximal to the overlying SMA, as well as a delay in transit of four to six hours through the gastroduodenal region. Standard diagnostic exams include abdominal and pelvic computed tomography (CT) scan with oral and IV contrast, upper gastrointestinal series (UGI), and, for equivocal cases, hypotonic duodenography. In addition, vascular imaging studies such as ultrasound and contrast angiography may be used to indicate increased bloodflow velocity through the SMA or a narrowed SMA angle.

Despite multiple case reports, there has been controversy surrounding the diagnosis and even the existence of SMA syndrome since symptoms do not always correlate well with radiologic findings, and may not always improve following surgical correction. However, the reason for the persistence of gastrointestinal symptoms even after surgical correction in some cases has been traced to the remaining prominence of reversed peristalsis in contrast to direct peristalsis.

Since females between the ages of 10 and 30 are most frequently afflicted, it is not uncommon for physicians to initially and incorrectly assume that emaciation is a choice of the patient instead of a consequence of SMA syndrome. Patients in the earlier stages of SMA syndrome often remain unaware that they are ill until substantial damage to their health is done, since they may attempt to adapt to the condition by gradually decreasing their food intake or naturally gravitating toward a lighter and more digestible diet.

It is a serious medical disorder and the mortality rate can be as high as 30%. The high mortality rate is likely a measure that this syndrome is seen in critically ill patients, rather than this syndrome being in itself lethal, although it can also present in otherwise healthy individuals (especially if the disorder was induced by pharmacologic agents). Drug induced megacolon (i.e. from Clozapine) has been associated with mortality as high as 27.5%.

Bile acid malabsorption is common in Crohn's disease but not always recognised. Most patients with previous ileal resection and chronic diarrhea will have abnormal SeHCAT tests and can benefit from bile acid sequestrants.

Patients with primary bile acid diarrhea are frequently misdiagnosed as having the irritable bowel syndrome as clinicians fail to recognize the condition. When SeHCAT testing is performed, the diagnosis of primary bile acid diarrhea is commonly made. In a review of 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable bowel syndrome patients, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant.

Estimates of the population prevalence taken from this review suggest that 1% of the adult population could have primary bile acid diarrhea (Type 2 bile acid malabsorption).

Attempts must be made to determine whether there is a secondary cause amenable to treatment.

Primary (idiopathic) intestinal pseudo-obstruction is diagnosed based on motility studies, x-rays and gastric emptying studies.

Multiple disorders are found in patients with radiation enteropathy, so guidance including an algorithmic approach to their investigation has been developed. This includes a holistic assessment with investigations including endoscopies, breath tests and other nutritional and gastrointestinal tests. Full investigation is important as many cancer survivors of radiation therapy develop other causes for their symptoms such as colonic polyps, diverticular disease or hemorrhoids.

Several methods have been developed to identify the disorder but there are difficulties with all of them. Fecal bile acid quantification is unpleasant for both the patient and laboratory. Diagnosis of bile acid malabsorption is easily and reliably made by the SeHCAT test. This nuclear medicine test involves two scans a week apart and so measures multiple cycles of bile acid excretion and reabsorption. There is limited radiation exposure (0.3 mSv). Retention of SeHCAT at 7 days is normally above 15%; values less than 15%, 10% and 5% predict respectively mild, moderate and severe abnormal retention and an increasing likelihood of response to bile acid sequestrants. This test is not licensed in the USA, and is underutilized even where it is available.

Older methods such as the C-glycocholic breath test are no longer in routine clinical use.

Measurement of 7α-Hydroxy-4-cholesten-3-one, a bile acid precursor, in serum, shows the increased bile acid synthesis found in bile acid malabsorption. This test is an alternative diagnostic means when available. Fasting blood FGF19 values may have value in the recognition of the disease and prediction of response.

Currently, there are two tests for evaluating BAM in the U.S. One test, currently available only for research purposes, measures serum levels of the marker 7α-hydroxy-4-cholesten-3-one (C4), a downstream product of CYP7A1. Plasma C4 levels increase when bile acid synthesis increases, and C4 levels are substantially elevated in BAM patients with a sensitivity and specificity of 90 percent and 79 percent, respectively. C4 levels have also been shown to correlate well with SeHCAT retention. This makes fasting serum C4 attractive as a screening test for BAM, although it can produce false-positives and false-negatives in patients who have liver disease or are taking statins.

The second test, which can now be clinically ordered, is the fecal bile acid excretion test. It quantifies individual and total bile acids in a 48-hour stool collection. Increased total fecal bile acids are seen in patients with chronic functional diarrhea and higher levels of CA and CDCA are associated with IBS-D.

A clinical validation involving 94 healthy volunteers, 60 patients with IBS-D and 28 patients with IBS with constipation (IBS-C) found that the sum of CA and CDCA concentrations above 3.7 percent were indicative of IBS-D with 72 percent sensitivity and 90 percent specificity. In addition, the upper limit of normal total fecal bile acid excretion over the 48 hours has been defined.

The current gold standard diagnostic test for EE is intestinal biopsy and histological analysis. Histological changes observed include:

- Villous blunting

- Crypt hypertrophy

- Villous fusion

- Mucosal inflammation

However, this procedure is considered too invasive, complex and expensive to be implemented as standard of care. As a result, there are various research efforts underway to identify biomarkers associated with EE, which could serve as less invasive, yet representative, tools to screen for and identify EE from stool samples.

In an effort to identify simple, accurate diagnostic tests for EE, the Bill and Melinda Gates Foundation (BMGF) has established an EE biomarkers consortium as part of their Global Grand Challenges initiative (specifically, the Discover Biomarkers of Gut Function challenge).

So far, various biomarkers have been selected and studied based on the current understanding of EE pathophysiology:

- Gut permeability/barrier function

- Dual sugar permeability (lactose-to-mannitol ratio)

- Intestinal inflammation

- Alpha-1 anti-trypsin

- Neopterin

- Myeloperoxidase

- Exocrine (hormonal) markers

- Bacterial translocation markers

- Endotoxin core antibody

- Markers of systemic inflammation

- Alpha-1 glycoprotein

- C-reactive protein (CRP)

It is postulated that the limited of understanding of EE is partially due to the paucity of reliable biomarkers, making it difficult for researchers to track the epidemiology of the condition and assess the efficacy of interventions.

Delay in the diagnosis of SMA syndrome can result in fatal catabolysis (advanced malnutrition), dehydration, electrolyte abnormalities, hypokalemia, acute gastric rupture or intestinal perforation (from prolonged mesenteric ischemia), gastric distention, spontaneous upper gastrointestinal bleeding, hypovolemic shock, and aspiration pneumonia.

A 1-in-3 mortality rate for Superior Mesenteric Artery syndrome has been quoted by a small number of sources. However, after extensive research, original data establishing this mortality rate has not been found, indicating that the number is likely to be unreliable. While research establishing an official mortality rate may not exist, two recent studies of SMA syndrome patients, one published in 2006 looking at 22 cases and one in 2012 looking at 80 cases, show mortality rates of 0% and 6.3%, respectively. According to the doctors in one of these studies, the expected outcome for SMA syndrome treatment is generally considered to be excellent.

Symptoms of short bowel syndrome are usually addressed with medication. These include:

- Anti-diarrheal medicine (e.g. loperamide, codeine)

- Vitamin, mineral supplements and L-glutamine powder mixed with water

- H2 blocker and proton pump inhibitors to reduce stomach acid

- Lactase supplement (to improve the bloating and diarrhoea associated with lactose intolerance)

In 2004, the USFDA approved a therapy that reduces the frequency and volume of total parenteral nutrition (TPN), comprising: NutreStore (oral solution of glutamine) and Zorbtive (growth hormone, of recombinant DNA origin, for injection) together with a specialized oral diet. In 2012, an advisory panel to the USFDA voted unanimously to approve for treatment of SBS the agent teduglutide, a glucagon-like peptide-2 analog developed by NPS Pharmaceuticals, who intend to market the agent in the United States under the brandname Gattex. Teduglutide had been previously approved for use in Europe and is marketed under the brand Revestive by Nycomed.

Surgical procedures to lengthen dilated bowel include the Bianchi procedure, where the bowel is cut in half and one end is sewn to the other, and a newer procedure called serial transverse enteroplasty (STEP), where the bowel is cut and stapled in a zigzag pattern. Heung Bae Kim, MD, and Tom Jaksic, MD, both of Children's Hospital Boston, devised the STEP procedure in the early 2000s. The procedure lengthens the bowel of children with SBS and may allow children to avoid the need for intestinal transplantation. As of June 2009, Kim and Jaksic have performed 18 STEP procedures. The Bianchi and STEP procedures are usually performed by pediatric surgeons at quaternary hospitals who specialize in small bowel surgery.

After the initial diagnosis of Barrett's esophagus is rendered, affected persons undergo annual surveillance to detect changes that indicate higher risk to progression to cancer: development of epithelial dysplasia (or "intraepithelial neoplasia").

Considerable variability is seen in assessment for dysplasia among pathologists. Recently, gastroenterology and GI pathology societies have recommended that any diagnosis of high-grade dysplasia in Barrett be confirmed by at least two fellowship-trained GI pathologists prior to definitive treatment for patients. For more accuracy and reproductibility, it is also recommended to follow international classification system as the "Vienna classification" of gastrointestinal epithelial neoplasia (2000).

The presence of goblet cells, called intestinal metaplasia, is necessary to make a diagnosis of Barrett's esophagus. This frequently occurs in the presence of other metaplastic columnar cells, but only the presence of goblet cells is diagnostic. The metaplasia is grossly visible through a gastroscope, but biopsy specimens must be examined under a microscope to determine whether cells are gastric or colonic in nature. Colonic metaplasia is usually identified by finding goblet cells in the epithelium and is necessary for the true diagnosis.

Many histologic mimics of Barrett's esophagus are known (i.e. goblet cells occurring in the transitional epithelium of normal esophageal submucosal gland ducts, "pseudogoblet cells" in which abundant foveolar [gastric] type mucin simulates the acid mucin true goblet cells). Assessment of relationship to submucosal glands and transitional-type epithelium with examination of multiple levels through the tissue may allow the pathologist to reliably distinguish between goblet cells of submucosal gland ducts and true Barrett's esophagus (specialized columnar metaplasia). Use of the histochemical stain Alcian blue pH 2.5 is also frequently used to distinguish true intestinal-type mucins from their histologic mimics. Recently, immunohistochemical analysis with antibodies to CDX-2 (specific for mid and hindgut intestinal derivation) has also been used to identify true intestinal-type metaplastic cells. The protein AGR2 is elevated in Barrett's esophagus and can be used as a biomarker for distinguishing Barrett epithelium from normal esophageal epithelium.

The presence of intestinal metaplasia in Barrett's esophagus represents a marker for the progression of metaplasia towards dysplasia and eventually adenocarcinoma. This factor combined with two different immunohistochemical expression of p53, Her2 and p16 leads to two different genetic pathways that likely progress to dysplasia in Barrett's esophagus.

The diagnosis is usually confirmed by biopsies on colonoscopy. Fecal calprotectin is useful as an initial investigation, which may suggest the possibility of IBD, as this test is sensitive but not specific for IBD.

There are multiple large-field, multi-country research initiatives focusing on strategies to prevent and treat EE.

- The MAL-ED project

- The Alive and Thrive nutrition project

- The Sanitation, Hygiene and Infant Nutrition Efficacy (SHINE) Trial (ClinicalTrials.gov identifier: NCT01824940)

- The WASH Benefits Study