Best Practice & Research Clinical Gastroenterology 30 (2016) 225e235

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Best Practice & Research Clinical

Gastroenterology

Assessment of intestinal malabsorption

K. Nikaki, Medical Degree, MRCPCH, Clinical Research Fellow,
G.L. Gupte, MD (Paeds India), DNB (Paeds India),
MRCPI, Consultant Paediatric Hepatologist *
Paediatric Liver Unit (including Small Bowel Transplantation), Birmingham Children's Hospital NHS
Foundation Trust, Steelhouse Lane, Birmingham, B4 6NH, UK

a b s t r a c t
Keywords:
Intestinal malabsorption Significant efforts have been made in the last decade to either
Small bowel malabsorption standardize the available tests for intestinal malabsorption or to
Carbohydrate malabsorption develop new, more simple and reliable techniques. The quest is
Small bowel bacterial overgrowth still on and, unfortunately, clinical practice has not dramatically
Fat malabsorption changed. The investigation of intestinal malabsorption is directed
Protein losing enteropathy
by the patient's history and baseline tests. Endoscopy and small
Plasma citrulline level
bowel biopsies play a major role although non-invasive tests are
favored and often performed early on the diagnostic algorithm,
especially in paediatric and fragile elderly patients. The current
clinically available methods and research tools are summarized in
this review article.
© 2016 Elsevier Ltd. All rights reserved.

Introduction

The investigation of intestinal malabsorption is guided by the clinical presentation and findings.
Normal digestion may be divided in the intraluminal phase, mucosal phase and post-absorptive phase
[1]. During the intraluminal phase, the pancreatic and biliary secretions hydrolyse and solubilise the
dietary fats, proteins and carbohydrates. Fat malabsorption is a cardinal sign of these disorders. During
the mucosal phase, the brush border enzymes play a pivotal role in the hydrolysis of the disaccharides
and peptides. Primary mucosal diseases, extensive intestinal resection and lymphomas result in
malabsorption of all nutrients. During the post-absorptive phase, lymphatic system obstruction may

* Corresponding author. Tel.: þ44 121 333 8255; fax: þ44 121 33 8251.
E-mail address: girish.gupte@bch.nhs.uk (G.L. Gupte).

http://dx.doi.org/10.1016/j.bpg.2016.03.003
1521-6918/© 2016 Elsevier Ltd. All rights reserved.
226 K. Nikaki, G.L. Gupte / Best Practice & Research Clinical Gastroenterology 30 (2016) 225e235

Table 1
Levels of investigations for intestinal malabsorption.

1st Level of investigations:

A. Blood tests: a. Full blood count, Blood film
b. Renal function
c. Bone profile
d. Liver Function Tests (incl. Albumin and INR)
e. Thyroid Function Tests
f. Coeliac serology
g. CRP/ESR
B. Stool tests: a. Stool microscopy and culture
b. Stool for ova, cysts and paracytes
c. C. difficile
d. Faecal occult blood test
e. Faecal Calprotectin
2nd level of Investigations:
A. Blood tests: a. Vitamin levels (Vit A, D, E, B12)
b. Serum elements (Mg, Zn, Se, Cu, Mn)
c. Iron studies
d. Lipid studies
B. Stool tests: a. Stool pH and reducing substances
b. Faecal fat globules
c. Faecal alpha1 antitrypsin (a1-AT)
d. Faecal elastase
3rd level of Investigations:
A. Endoscopy: a. Duodenal biopsies
b. Terminal ileum biopsies
c. Jejunal aspirate for culture
B. Imaging a. Abdominal USS and Xray
b. CT abdomen
c. Barium meal and follow through
4th level of Investigations:
A. Hydrogen breath test, ± Lactose tolerance test, ± Urine galactose
B. Genetics for CHO malabsorption
C. Serum D-lactate
D. 13C- mixed-chain triglyceride breath test
E. SeCHAT, ± Serum C4
F. Schilling test (with and without intrinsic factor)
G. VCE
H. Technitium-99m human serum albumin scintigraphy

lead to steatorrheoa and protein loosing enteropathy. The patient's detailed history is critically
important along with the results of baseline blood and stool investigations (see Table 1) which then
guides further specialised investigations. Below we will discuss the clinical approach and then
investigation of specific nutrient malabsorption (carbohydrate, fat, protein, vitamin and mineral) with
a brief synopsis of the specific tests that aid in the investigation and assessment of intestinal
malabsorption.

Clinical approach

The clinical features of the child depend on the age of presentation and the severity of the mal-
absobred nutrient. The common features in children with malabsorption are: diarrhea, faltering
growth, abdominal distension or bloating and towards the end loss of subcutaneous fat with promi-
nent skin folds. The presentation can be more dramatic in toddlers because of lower energy reserves as
well as the majority of the energy contributes towards weight gain and linear growth. In the older
children it affects linear growth more commonly. Occassionally the signs on examination may give a
clue to the underlying nutrient deficiency i.e Edema in protein losing enteropathy, abdominal
distention (bloating) and perianal excoriation with carbohydrate malabsoprtion. Anorexia and lethargy
 K. Nikaki, G.L. Gupte / Best Practice & Research Clinical Gastroenterology 30 (2016) 225e235 227

may be seen in malabsorption, but occasionally children may have hyperphagia to compensate for the
fecal protein and energy losses.

Investigations for specific Nutrient absorption

Carbohydrates

Faecal reducing substances

Measurement of stool reducing substances, using a Clinitest reagent or Benedict's test [2] with and
without hydrolysis, is particularly useful in paediatrics. The test's name comes from the ability of sugars
to act as a reducing agent (reducing cupric ions to cuprous ions). The results of this chemical reaction
and the color of the obtained precipitate are used in a semi-quantitative way to determine the presence
of reducing sugars. A green precipitate indicates a 0.5% concentration of reducing sugars (þ), a yellow
precipitate a 1% concentration (þþ), an orange precipitate a 1.5% concentration (þþþ), a red precip-
itate a 2% concentration (þþþþ). Reducing sugars are simple sugars and include all monosaccharides
(glucose, fructose and galactose) and most disaccharides (lactose and maltose; sucrose is a non-
reducing sugar and only becomes one after being hydrolysed) [3]. Ambient transport temperatures
result in growth of bacteria, which can in turn result in false-negative results. A stool pH level is
measured during the test and a pH of <5.5 indicates carbohydrate malabsorption, even in the absence
of reducing substances. The test has poor sensitivity from diaper stools because fluid is reabsorbed into
the diaper. Testing of only the solid portion of the stool will give a falsely-low reading since the liquid
portion of the stool contains the water-soluble sugars. A per-rectal insertion of catheter may be
required to collect the stools on rare occasions when an appropriate stool sample cannot be obtained.
Increased reducing substances in stool (þþ) are consistent with primary or secondary disaccharidase
deficiency and intestinal monosaccharide malabsorption. A positive result should be followed by a
chromatogram to further characterize the type of sugar present in the stool. It is important to
remember that other agents e.g salicylates, penicillin, choral hydrate, isoniazid, and cephalosporins
may interfere the results.

Hydrogen breath test

Hydrogen-breath tests are based on the concept that colonic bacterial fermentation produces gases
that are diffused in the blood stream and exhaled by breath, where it can be detected. The 1st Rome H2-
Breath testing consensus-working group was convened in 2007 and offered recommendations for
clinical practice about indications and methods of H2-breath testing in gastrointestinal diseases [4].
More than 99% of intestinal gas is composed of five non-odorous gases (N2, O2, CO2, H2 and CH4). H2 and
CH4 are exclusive products of bacterial metabolic processes in the bowel. During fasting, H2 production
is low in normal subjects, but intraluminal bacteria can produce appreciable amounts of H2 after
ingestion of fermentable and undigested substrates, mainly carbohydrates. This also occurs in small
bowel diseases and carbohydrate malabsorption, where high amounts of substrate reach the colon and
become available for bacterial fermentation. H2 is rapidly absorbed in the bloodstream and is excreted
by the lungs; the rationale behind H2-breath test, which is widely used to detect carbohydrate
malabsorption [5]. H2-breath detection is influenced by three main factors; the faecal pH [6], the
composition of the colonic microflora, in regards to methanogenic and sulphate-reducing bacteria, and
H2 faecal tension which depends on colonic motility [7]. More specifically, H2 gas production pro-
gressively declines as colonic pH is lowered, whilst up to 30% of adult population are ‘CH4 producers’,
harboring high concentrations of methanogenic flora, able to consume large quantities of hydrogen to
produce methane. Thus, a methane breath test could theoretically improve the test's accuracy by
reducing the number of false negative results. However, the prevalence of hydrogen non-producers is
inversely correlated to the test duration [8,9], which suggests that a variable gastrointestinal transit of
the substrate may be responsible for false negative results. The added clinical value of methane breath
test is yet to be proven as to date the data are inconclusive [4,10,11]. False negative hydrogen breath test
results could also be due to recent use of antibiotics. False positive results are less frequent and most
likely due to small bowel bacterial overgrowth [12]. Although H2-breath tests are low cost and simple
to use, their methodology is not yet fully standardized [4,13]. With this point in mind, the sensitivity
228 K. Nikaki, G.L. Gupte / Best Practice & Research Clinical Gastroenterology 30 (2016) 225e235

and specificity of lactose breath test is around 77.5% and 97.6% respectively [4]. In adults, 50 g of lactose
have been used in the validation studies of breath testing; but, as this is arguably a very high dose of
lactose, 25 g is the current recommended dose. The recommended test duration is 4 hours, with 30 min
intervals for sampling and a cut-off value of 20 ppm above the baseline. In children, the recommended
dose for lactose is 1g/kg (max 25 g), 3 hours test duration, with 30 min intervals for sampling and
20 ppm above the baseline as the diagnostic cut-off value [4]. Fructose and sorbitol breath tests have
limited use in clinical practice due to lack of validation studies [4,11].

Genetics
Identification of C/T-13910 and G/A-22018 mutations, located upstream the gene encoding the
lactase-phlorizin hydrolase (LPH), has been suggested as a useful tool for lactase non-persistence in
Caucasian patients [14]. The 13910*T genotype correlated closely (86e95%) with other tests for
lactose malabsorption in European countries [15,16]. A heterozygous genotype has to be considered a
negative test result, as lactose malabsorption due to lactase non-persistence is a recessive condition.
Identification of these mutations is of limited use at present in certain African, Arabic, or Asian sub-
populations where lactase persistence may be linked to different polymorphisms. Also, genetic testing
will be negative in patients with secondary lactase deficiency [17]. As no information about clinical
symptoms of lactose intolerance is obtained during testing its clinical relevance has been criticized
[18].

Lactose tolerance test

A lactose tolerance test involves measurement of blood glucose after ingesting 50 g of lactose.
Failure of the blood glucose to raise more than 20 mg/dl within 3 hours implies failed absorption of the
carbohydrate and thus an abnormal result [19,20]. The lactose tolerance test is usually performed at the
same time as the hydrogen breath test but has a lower sensitivity and specificity [17].

Urine galactose
Ingested lactose is hydrolyzed by intestinal lactase, producing galactose, which is then absorbed and
rapidly metabolized by the liver. Following ingestion of 50 g of lactose, a high galactose concentration
in the urine signifies adequate activity of intestinal lactase, whereas a low urinary galactose concen-
tration suggests that the patient is hypolactasic [21e23].

Small bowel mucosal biopsies

The biochemical disaccharidase assay is the gold standard diagnostic test for hypolactasia (lactase
<10 g/U) [4,24]. However, it seems too invasive and its results may be influenced by the irregular
dissemination of lactase activity throughout the small intestine mucosa [25]. Genetic testing for lactase
polymorphism (see above) has a high accuracy in predicting lactase persistence/non-persistence, but it
is expensive and does not indicate the lactase activity at the moment the subject is tested [4,26]. Both
tests are cumbersome in clinical practice. The use of Lactose Intolerance Quick Test has been suggested
recently in place of the disaccharidase assay and it has been shown to have excellent sensitivity and
good specificity [26] with excellent concordance compared to lactulose breath test [27].

D-xyloseabsorption test
D-xylose
is a monosaccharide that is absorbed unchanged by the duodenum and jejunum and is
metabolized minimally. It's absorption reflects the total surface area of the jejunum and the mucosal
permeability rather than carbohydrate absorption per se [28]. D-xylose test can also help in dis-
tinguishing between intestinal (abnormal excretion) and pancreatic (normal excretion) causes of mal-
absorption. There are two factors that affect the accuracy of the D-xylose absorption test-rate of ab-
sorption by the intestine and rate of excretion by the kidneys. Thus patients with renal insufficiency
may give false low results. Reportedly the standard 25 g D-xylose test in adults has a 95% sensitivity and
specificity for small bowel malabsorption when a 1hr serum sample and 5hr urine collection is used
[29]. The urine collection though seams to be offering more reliable results than the 1hr serum
sampling [30]. The lower limit of normal for the 5-h urine collection is 4 g; for the 1-h serum value the
 K. Nikaki, G.L. Gupte / Best Practice & Research Clinical Gastroenterology 30 (2016) 225e235 229

lower limit of normal is 25 mg/dl. In paediatrics, a 5 g loading dose is used and a 1hr serum sample
taken as urine collection is more challenging. The lower limit of normal is 20 mg/dl [29].
In small bowel intestinal transplant, the D-xylose absorption test has been used for monitoring of
the graft's function, but the presence of renal impairment in these patients and the large variation of
D-xylose values between individuals means that the test can only be used for monitoring purposes
rather than as a true marker of the intestinal graft function [31].
D-xylose has also been used as a substrate for breath tests. 14 C-xylose and 13 C-xylose breath has
been evaluated for the diagnosis of small bowel bacterial overgrowth. Although these tests appear to
do better than glucose and lactulose breath tests, their sensitivity still varies a lot [32].

Bacterial Overgrowth
Small intestinal bacterial overgrowth (SIBO) and sugar malabsorption are associated as they can
either share the same causative factors; such as impaired motility, congenital and acquired anatomical
disorders, iatrogenic blind loop formation and immunodeficiencies which would favor an imbalance in
the bacterial growth of the small bowel and an impairment in the enterocyte function, or have a direct
cause and effect relationship [4,33]. Small bowel bacterial overgrowth is defined quantitative as the
presence of at least 105 colony-forming units per ml of jejunal aspirate although the qualitative
composition of the flora is important as well (mainly in the terms of respiratory tract and colonic
bacteria). A jejunal aspirate culture is considered as the “gold standard” although the procedure is not
standarised (amount of aspirate, site of aspiration and microbiological parameters) and fails to capture
the “distal”, ileal, bacterial overgrowth. The glucose and lactulose breath test have also been used in the
diagnosis of SIBO as these are non-invasive tests. Unfortunately these tests in SIBO have poor sensitivity
(30e40%) but good specificity (80%) [34]. The most frequently used cut-off value for test positivity is
10e12 ppm above the basal value. The glucose breath test shows a single “early” peak of hydrogen
excretion, while the lactulose breath test shows two distinct hydrogen excretion peaks: the first “early”
peak due to the small bowel microflora activity and the second “late” peak due to the colonic bacterial
metabolism. The two peak theory on the lactulose breath test works on the assumption of a normal
intestinal transit time and so it is argued that only glucose breath test should be used in clinical practice
[34]. D-lactatic acidosis secondary to SIBO has been reported in paediatric patients [35,36] and can be
used as an indirect marker of SIBO diagnosed by measuring D-lactate in serum. This is more relevant in
patients with positive neurological findings and a high anion gap acidosis on the blood gas. In clinical
practice, a trial with oral antibiotics that have minimal absorption in the bloodstream is sometimes
preferred as a diagnostic test, especially in patients with known pre-desposing factors. Oral genta-
mycin, amikacin and metronidazole can be used for this cause.

Fat malabsorption

Faecal fat test (FFT)

The 72-hour stool for faecal fat test (Van de Kamer method [37]) has been historically considered
the gold standard for the diagnosis of fat malabsorption. The need for dietary fat control, the inability to
correct for incomplete faecal collection and the lack of quality control procedures to ensure analytical
reliability reduces its clinical value [38].

Faecal fat globules

Determination of presence of faecal fat globules with faecal microscopy (Sudan stain of faecal fat) is
not well standardized but has the advantage of detecting faecal triglycerides and fatty acids, which are
mainly of dietary origin; other faecal fat lipids include phospholipids and cholesteryl esters, which
largely originate from the turnover of intestinal epithelial cells and gut bacteria [39].

Breath testing
The 14C-triolein test, the measurement of breath 14CO2 after a dose of a carbonyl-labelled triglyc-
eride added to a fatty meal, has a sensitivity of 85% and specificity of 93% for fat malabsorption [40].
Various protocols are used with the amount of fat load used playing a role in the timing of the peak
14
CO2 breath level. Disadvantages of the study include difficulties in transporting and analysing
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radioisotopic labelled samples and requirement for a scintillation counter as well as it tends to be a
qualitative test rather than a quantitative test. Thus, application of stable isotopes, such as 13C-sub-
strates, is gaining ground. A breath test using 13C- mixed-chain triglyceride [1,3-distearyl, 2(carbox-
yl-13C) octanoyl glycerol] has been applied to children [41,42] and adults [43]. The test is designed to
assess intraluminal pancreatic lipase activity (i.e. exocrine pancreatic insufficiency), therefore it is not a
substitute for faecal fat measurement. The reported sensitivity of the test is 89% and specificity is 81%
[43].

The serum retinyl palmitate (RP) test

Vitamin A is a fat-soluble vitamin that parallels the absorption of lipids. Retinyl palmitate, an
equivalent to retinol, has been trialed as a marker of fat malabsorption but has failed to discriminate
between patients and healthy volunteers [44]. The quest for an easy to measure, sensitive blood marker
for fat malabsorption is still on.

Assessment for pancreatic exocrine insufficiency

The most sensitive, direct test for the diagnosis of pancreatic exocrine insufficiency is based on
aspiration of the pancreatic contents during secretin or secretin-cholecystokinin/cerulein adminis-
tration; this test is only available in a few centres as it is invasive and is not indicated in clinical practice
[45].

Faecal elastase-1
The most commonly used, readily available, test in clinical practice for the assessment of
pancreatic exocrine insufficiency is the faecal elastase test. It is based on a monoclonal antibody test
and the analysis is made on a single stool sample. The diagnosis of exocrine pancreatic insufficiency
is made when the faecal elastase-1 concentration is less than 200 mg/g and severe pancreatic
insufficiency when it is less than 100 mg/g [45]. In severe exocrine pancreatic insufficiency the
sensitivity of the test ranges between 73 and 100%. But for mild to moderate exocrine pancreatic
insufficiency it is much lower (0e47%) [46]. Fecal elastase-1 can give a false positive result during
episodes of diarrhea. The other disadvantage is that it does not help to differentiate between pri-
mary exocrine pancreatic insufficiency and secondary pancreatic insufficiency to intestinal villous
atrophy.

Faecal chymotrypsin
Faecal chymotrypsin has a lower sensitivity for exocrine pancreatic insufficiency [47] and therefore
it is not used routinely in clinical practice. Moreover, pancreatic enzyme replacement therapy needs to
be discontinued prior testing, which is not the case for faecal elastase-1 [45].

The malabsorption blood test

The malabsorption blood test is a novel tool for the assessment of fat malabsorption in cystic fibrosis
and pancreatic insufficiency. A fat loading test meal, that includes pentadecanoic acid (PA), a free fatty
acid, and triheptadecanoic acid (THA), a triglyceride that requires pancreatic lipase for absorption of
the heptadecanoic acid (HA), is offered to the patient. PA and HA levels in plasma are then measured in
order to determine their absorption status. Further research is required to allow clinical applicability of
the method [48,49].

Bile salts malabsorption

There are four tests that directly measure the bile acids, the 14C-glycocholate breath and stool test,
individual faecal bile acid levels, the 75Selenium HomotauroCholic Acid Test (SeHCAT) and the 7a-
hydroxy-4-cholesten-3-one (C4). Out of these, the 14C-glycocholate breath and stool test is too labo-
rious and is no longer in wide clinical use, while measuring individual bile acids in faecal samples is
technically difficult and not widely available either [50]. SeHCAT is a nuclear medicine test that uses
Selenium-75-homocholic acid taurine for the investigation of bile acid malabsorption and measure-
ment of bile acid pool loss. More than 15% retention of 75Selenium at 7 days post ingestion of the
gamma radiolabelled bile acid is consistent with a normal result. Mild bile acid malabsorption is
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considered when there is 10e15% retention, moderate in 5e10% retention and severe in <5% retention
[51]. At present, a trial of treatment and assessment of response is still considered more cost-effective
and is the preferred route in clinical practice [52]. Serum C4 is an intermediate in the classical pathway
of bile acid synthesis. In bile acid malabsorption, there is up-regulation of the enzymes in the pathway
with accumulation of the C4. Serum C4 is relatively stable and can be measured by high-performance
liquid chromatography [53]. Using SeCHAT as the gold standard, C4 has been shown to have a positive
predictive value of 74% and a negative predictive value of 98% [54]. Clinical application of this test in
paediatrics is very useful. The advantages of the SeHCAT test are that there is minimal radiation
exposure to other organs, can predicts response to bile acid sequestrant if used for therapy, but does
involve two patient visits. Only recently were normal values established for a paediatric population
[55].

Protein malabsorption and protein losing enteropathy

Protein losing enteropathy should be considered in individuals with edema and hypolbuminemia,
but without documented evidence of liver or renal disease. Proteins are hydrolysed and only bi- and
tri-peptides and amino acids are transported across the intestinal endothelium [56]. Measurement of
protein absorption is difficult and unreliable; it is, therefore, rarely advocated in clinical settings.
Protein malabsorption is associated with carbohydrate and fat malabsorption. Radiolabelled albumin
and faecal clearance of alpha 1-antitrypsin (a1-AT) have been used for the diagnosis of protein
malabsorption and intestinal losses. 51Cr- and 125I- radiolabelled albumin excretion were introduced
around 1960 and were almost fully replaced by the measurement of faecal a1-AT [57] by 1990, as their
use was limited by the need for daily collection of blood and faeces for 6e10 days and exposure to
radioactive products. a1-AT has a similar molecular weight to albumin and is synthesized by the liver. It
is minimally digested by intestinal proteases and therefore its faecal concentration has been used as a
measure of protein leakage in the bowel. The a1-AT concentration is less reliable but easier to use
compared to the faecal a1-AT clearance, as it obviates the need for a stool collection and measurement
of serum levels. As acid destroys a1-AT, it only evaluates losses distal to the pylorus. Moreover, in the
presence of gastrointestinal bleeding the test can be false positive [58].

Vitamin B12 malabsorption

Vitamins and minerals are absorbed throughout the small bowel but the absorption of Vitamin B12
is specific to the terminal ileum and the presence of intrinsic factor. The Schilling test in two stages
(without and with intrinsic factor) allows for the differentiation between pernicious anaemia and
Vitamin B12 malabsorption [59].

Plasma citrulline concentration

Citrulline is produced almost exclusively by the enterocytes of the small bowel mucosa as an end
product of glutamine nitrogen metabolism. Normally most of citrulline is converted to arginine by the
kidneys. Plasma citrulline levels have been suggested as a marker of enterocyte mass [60,61]. Whether
fasting plasma citrulline concentrations correlate well to the degree of enterocyte mass decrease in
small intestinal disorders has been controversial. In patients with severe extensive villous atrophy
(proximal and distal) plasma citrulline concentration is severely decreased (<10 mmol/l) [62]. On the
other hand, the association of plasma citrulline with the remnant small bowel length is not linear but
quadratic, which means that decreased plasma citrulline concentrations mainly only reflect the
extreme ends of the disease spectrum [63]. Recently, the citrulline generation test has been suggested
as an alternative option. The test dynamically measures the conversion rate of glutamine into citrulline
over time, following administration of glutamine as a dipeptide with alanine [64,65]. Further research
is required to establish whether this should become standard practice in the assessment of small
bowel's absorptive capacity.
232 K. Nikaki, G.L. Gupte / Best Practice & Research Clinical Gastroenterology 30 (2016) 225e235

Other investigations

Endoscopy and VCE

Small bowel biopsies have been considered the “gold standard” for the diagnosis of carbohydrate
malabsorption (as discussed above). Fat malabsorption can also be histologically assessed following a
fat loading meal. Assessment of villous length and architecture, crypt length and changes, alongside the
lamina propria infiltrate are diagnostic for the different types of enteropathy [66]. The main limitation
of the upper gastrointestinal tract endoscopy is the inability to reach beyond the duodenum, which can
now be overcome by double balloon enteroscopy. This is a specialized endoscopic procedure and quite
cumbersome, which is usually reserved for obscure causes of gastrointestinal bleeding and therapeutic
interventions. Video capsule endoscopy (VCE) can offer a visual only assessment of the entire small
bowel and limitations are that a biopsy cannot be obtained. However, it may help in target specific
areas of GI tract with the help of a double balloon enteroscopy. In older children the capsule can be
swallowed, but in younger children it needs to be placed endoscopcially [67]. In children with a high
index of suspicion of stricture, it should be avoided.

Radiology

The different techniques used are.

1. Plain abdominal film

2. Ultrasound,Contrast-entranced ultrasound and new ultrasound techniques
3. Small-bowel follow-through.
4. Enteroclysis.
5. CT enteroclysis, CT enterography.
6. MR Enteroclysis/MR Enterography

Radiological assessment of the small bowel can be done in the first place through a plain
abdominal film and ultrasound. Although ultrasound has the advantages of no radiation, portable,
being cheap compared to other imaging techniques, the major limiting factor for its widespread
usage is the experience of the Ultrasonographer and interobserver variability. Contrast meal and
follow through are still used in some paediatric patients who would otherwise need a general
anaesthetic in order to tolerate any cross sectional imaging and is also particularly useful if there is
suspicion of strictures or dilatation. Small bowel magnetic resonance enterography (MR enter-
ography) is gaining ground over computed tomography (CT) as it allows better tissue contrast and
excellent tissue visualization of the entire bowel without any overlapping loops [68]. The other
advantages of MR enterography are the minimal radiation especially in children who need frequent
follow-up during whole life. Enteroclysis is a technique which is gaining popularity in defining the
subtle mucosal abnormalities A nasojejunal tube under fluoroscopic guidance is introduced, in the
duodeno-jejunal flexure. Administration of barium suspension followed by 0.5% methyl cellulose
through the tube is performed manually or by an automatic pump. The concept is that enteroclysis
causes small-bowel loops to distend, which then allows for better visualization of subtle
abnormalities.

Practice Points
The sequence of investigations of a patient with suspected malabsorption largely depends on
the patient's age and personal history. Below (Table 1) we separate the available investigations
in different levels trying to indicate a stepwise approach where the investigations that follow
are specialized and their necessity depends on the results of the investigations on the previous
level.
 K. Nikaki, G.L. Gupte / Best Practice & Research Clinical Gastroenterology 30 (2016) 225e235 233

Research Agenda

1. Standardization of hydrogen breath studies and outcome studies.

2. Identification of different genetic polymorphisms for lactase non-persistence in African,
Arabic, or Asian subpopulations.
3. Establish the role and use of Lactose Intolerance Quick Test in small bowel biopsies.
4. Microbiome studies for small bowel bacterial overgrowth in order to identify the micro-
biome dys-biosis and target antibiotic treatment.
5. Identify a biomarker in fat malabsorption that would be easier to measure compared to the
currently available methods.
6. Identify a biomarker that would better discriminate between mild and moderate levels of
pancreatic insufficiency and confirm predictive value with outcome studies.
7. Outcome studies for the role of SeHCAT in the investigation of chronic diarrhea and treat-
ment with bile acid binders.
8. Further establish the predictive value of plasma citrulline concentration in the assessment of
small bowel's absorption capacity.
9. Elucidate the protein absorption pathways and the interaction of peptides with the immune
system.

Enteroclysis has been shown to be highly accurate, with a sensitivity of 93% and specificity of 97% in
diagnosing small bowel diseases & permits detection of partly obstructive or non-obstructive lesions
that may not be demonstrated with cross-sectional imaging techniques. The overlapping bowel loops
may limit its usefulness but is overcome by the use of CT enteroclysis or MR enteroclysis.
Technetium-99m human serum albumin scintigraphy has been suggested as a simple and sensitive
method for not only to diagnosing protein losing enteropathy, but also to localize the site of protein loss
in the gastrointestinal tract [69,70].

Summary

Investigating the small bowel's absorption is a fascinating and relevant not only to gastroenterol-
ogists but all specialists, as nutrition plays a pivotal role on outcomes in all fields of medicine. The
clinical algorithm for investigating intestinal malabsorption depends on whether all nutrient pathways
are affected or not. The methods that are currently available are indirect methods of assessing the
different pathways of nutrient absorption. The quest for minimally invasive, sensitive and specific
methods is still on. This becomes even more important as more paediatric patients with short bowel
syndrome survive and reach adulthood. Moreover, small bowel transplantation is evolving and gets
established in paediatric and adult patients.

Conflict of interest

None.

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