Malabsorption, maldigestion and lactose intolerance

• Malabsorption means nutrients fail to reach the blood or lymph after eating; maldigestion means food is not broken down into absorbable small molecules. In practice the two overlap, and either one can present as weight loss, bulky pale stools, vitamin deficiencies, anaemia or low albumin.
• The causes fall into three groups: problems before the mucosa (pancreatic enzyme deficiency, bile salt deficiency, bacterial overgrowth, disaccharidase deficiency), problems in the mucosa (coeliac disease, tropical sprue, Whipple disease, Crohn disease, infections, radiation) and problems of transport or secretion.
• Steatorrhoea, weight loss, bloating, anaemia and the signs of fat-soluble vitamin deficiency are the classic clues. Investigations range from stool fat and faecal elastase to breath tests, coeliac serology, small bowel imaging and biopsy.
• Treatment is aimed at the cause: pancreatic enzymes for exocrine insufficiency, antibiotics for tropical sprue, giardiasis and bacterial overgrowth, a gluten-free diet for coeliac disease, targeted antibiotics for Whipple disease, and parenteral support with teduglutide for selected patients with short bowel.
• Lactose intolerance is the commonest and most benign form. It is an enzyme shortage, not an allergy; milk proteins are usually tolerated, and most people manage it with symptom-guided reduction rather than strict avoidance.

By the end of this page you should be able to:

1. Explain how fat, protein, carbohydrate, vitamins and minerals are normally digested and absorbed, and name the site for each.
2. Classify the causes of maldigestion and malabsorption as premucosal, mucosal or transport problems, and name a clue and a confirming test for each common cause.
3. Recognise the clinical presentation of malabsorption and connect each symptom to its mechanism.
4. Choose and interpret the first-line investigations for a patient with suspected malabsorption.
5. Outline the specific management of Whipple disease, tropical sprue, small intestinal bacterial overgrowth and short bowel syndrome.
6. Diagnose, investigate and manage lactose intolerance, and distinguish it from cow milk protein allergy.
7. Describe malabsorption in low-resource settings, including environmental enteric dysfunction.

The problem can occur before the mucosa, in the mucosa, or during transport and secretion. ^[1]

• Premucosal (flawed intraluminal digestion). The enzymes and the solvents needed to break food down are missing or misdirected. Examples are exocrine pancreatic insufficiency, bile salt deficiency, bacterial overgrowth and disaccharidase deficiency.
• Mucosal. The surface that absorbs is damaged or inflamed. Examples are coeliac disease, tropical sprue, Whipple disease, Crohn disease, infections, radiation enteritis, graft-versus-host disease and drug-induced enteropathy.
• Mucosal intracellular, postcellular and transport. The surface is present but nutrients cannot move through or leave the cell, or lymphatic drainage is blocked. Examples are lymphangiectasia, obstruction of lymphatic drainage, mesenteric ischaemia and defects of membrane transporters.

Malnutrition in this context means more than low weight. Micronutrient deficiency produces specific signs, and macronutrient deficiency produces protein-energy malnutrition with low albumin, oedema and loss of muscle. ^[1]

Food is broken down in stages. Chewing and salivary amylase start carbohydrate digestion. The stomach adds acid and pepsin for protein. The pancreas pours in enzymes that digest carbohydrate, fat and protein, and the liver contributes bile salts that solubilise fat. The small bowel then absorbs, and the colon salvages water, electrolytes and some nutrients.

The colon is not just a waste pipe. It salvages water, sodium, chloride, short-chain fatty acids, calcium, magnesium and several water-soluble vitamins plus vitamin K, and bacterial metabolism of malabsorbed carbohydrate produces gas that can distend and hurt. ^[1]

Several principles follow and are worth keeping in mind:

• Solubilisation is a prerequisite for absorption. Fat and fat-soluble vitamins need micelles; calcium needs acidification of the lumen. Loss of bile salts, as in extensive ileal resection, therefore causes combined fat and fat-soluble vitamin loss. ^[1]
• Enteric senses and motor function time the delivery and mixing of contents with secretions. Neural and hormonal signals coordinate secretion, absorption and motility. ^[1]
• Vitamin B12 absorption depends on intrinsic factor; iron requires reduction from ferric to ferrous form. ^[1]

Coeliac disease, tropical sprue and brush-border damage often affect the proximal small bowel first, so iron and folate deficiency may appear before steatorrhoea.

Malabsorption has no single worldwide incidence: it is a syndrome with many causes, and each cause has its own epidemiology. Some causes that were common a century ago, such as tropical sprue and small bowel tuberculosis, have mostly receded, while coeliac disease and Crohn disease are on the rise. ^[1] Exocrine pancreatic insufficiency is the commonest premucosal form, often from chronic pancreatitis or cystic fibrosis. Coeliac disease is the commonest mucosal form in many populations and should be suspected whenever malabsorption has no obvious explanation. ^[1]

Micronutrient malabsorption produces specific patterns that are often the presenting problem. ^[1]

Malabsorptive symptoms come from two mechanisms. Deficiency of a nutrient causes systemic signs: anaemia, weight loss, oedema from low albumin, bleeding, osteomalacia, infertility, neuropathy. Excess unabsorbed substrate left in the gut causes diarrhoea, steatorrhoea, bloating, abdominal pain and (with oxalate hyperabsorption) kidney stones. ^[1]

The colon compensates partly: bacteria ferment malabsorbed carbohydrate to short-chain fatty acids that the colon absorbs, salvaging calories, and the colon absorbs water-soluble vitamins and vitamin K. When protein loss or fat loss exceeds compensation, symptoms appear. ^[1]

Iron and folate are absorbed in the proximal small bowel, so diseases that attack the proximal mucosa (coeliac disease, tropical sprue, radiation) often produce iron and folate deficiency before steatorrhoea. Vitamin B12 and bile salts are absorbed in the terminal ileum, so ileal resection or Crohn ileitis produces megaloblastic anaemia and, through bile salt malabsorption, watery diarrhoea and sometimes kidney stones.

Patients rarely present with the word "malabsorption". The common presentations are:

• Chronic diarrhoea or loose stools, often greasy, pale, bulky and difficult to flush when steatorrhoea is present. Steatorrhoea means excess fat in the stool and usually becomes clinically obvious once fat absorption falls markedly.
• Weight loss and loss of appetite. In children, failure to grow or thrive.
• Bloating, flatulence, borborygmi and abdominal discomfort, especially after meals or with carbohydrate malabsorption.
• Fatigue and weakness; anaemia can be iron-deficient, megaloblastic, or both.
• Easy bruising or bleeding (vitamin K deficiency), bone pain or fractures (vitamin D and calcium), night blindness (vitamin A), neuropathy (B12 or folate).
• Oedema and ascites from low albumin in protein-losing enteropathy or severe malnutrition.
• Muscle cramps or tetany from hypocalcaemia.
• Menstrual disturbance, infertility, growth delay in children, neurological change or miscarriage.

Bloating and flatulence after lactose or fruit may dominate in disaccharidase deficiency; here weight loss and deficiency signs are absent. ^[1]

Look for wasting, loss of subcutaneous fat and temporal wasting. Examine the tongue for glossitis, the mouth corners for angular stomatitis, the eyes for night-blindness, and the skin for bruising, pallor, eczema or dermatitis herpetiformis. Check for peripheral oedema, ascites and signs of venous thrombosis. Test reflexes and vibration sense for B12 neuropathy. Abdominal examination is often normal; Crohn disease may give right-lower-quadrant tenderness or a mass, and lymphoma may give a mass. Perianal examination matters.

The main differentials are organic small bowel disease versus functional bowel disorder. A patient with IBS-like diarrhoea, bloating and no alarm features may have carbohydrate malabsorption. Red flags that point away from a functional diagnosis are weight loss, nocturnal diarrhoea, steatorrhoea, blood, anaemia, fever, onset after age fifty, family history of coeliac or inflammatory bowel disease, and abnormal inflammatory markers.

Other mimics include chronic pancreatitis with pain, pancreatic cancer with weight loss and new diabetes, thyrotoxicosis with diarrhoea, small bowel lymphoma, and tuberculosis in endemic regions.

A systematic approach from history, then baseline blood tests:

• Full blood count, ferritin, vitamin B12, folate, prothrombin time, albumin, calcium and phosphate, liver and cholestatic enzymes, electrolytes, renal function, and a lipid profile where steatorrhoea is present.
• Stool studies: microscopy for ova and parasites, especially Giardia; faecal elastase; faecal calprotectin if inflammation is suspected.
• Coeliac serology: tissue transglutaminase IgA together with total IgA. Add IgG-based assays if IgA deficient. ^[1]

• Fecal fat. The traditional reference test is a 72-hour stool collection on a standard fat diet. It quantifies steatorrhoea but does not say why. ^[1]
• Faecal elastase. A random stool test that is specific for exocrine pancreatic insufficiency. A level under 100 microg/g gives good evidence of exocrine insufficiency, and 100 to 200 microg/g is indeterminate. A normal result does not completely exclude pancreatic insufficiency, and a low result in a dilute or formed stool can be falsely low. ^[1]
• D-xylose test. Historically used to assess proximal mucosal absorption (25 g of D-xylose in water, with a 5-hour urine collection and 1-hour serum level). It has limited availability and is not currently recommended as a routine test. ^[1]
• Alpha-1 antitrypsin clearance. A marker of protein-losing enteropathy when the albumin is low without liver or renal disease. ^[1]

• Upper gastrointestinal endoscopy with duodenal biopsies for coeliac disease, tropical sprue, Whipple disease, giardiasis and immunodeficiency-related enteropathy. Endoscopic appearances miss about a third of coeliac disease, so biopsy is required even when the mucosa looks normal. ^[1]
• Video capsule endoscopy and, in selected complicated cases, double balloon enteroscopy to reach beyond the duodenum. ^[1]
• Colonoscopy with ileal biopsy and cross-sectional imaging (CT or MR enterography) for Crohn disease, lymphoma and stricture. ^[1]

Breath tests are non-invasive and useful for carbohydrate malabsorption and, in context, for bacterial overgrowth.

• Lactose or fructose breath test. After a dose of lactose (25 to 50 g for malabsorption diagnosis; 25 g for intolerance assessment), a rise of at least 20 ppm in hydrogen above baseline is a widely used cut-off for malabsorption, with very high specificity and moderate sensitivity; 10 ppm has slightly lower specificity and higher sensitivity. The test is best combined with a symptom questionnaire, because malabsorption and intolerance are not identical. ^[8]
• Bacterial overgrowth. Breath tests for small intestinal bacterial overgrowth are currently discouraged as a routine diagnostic tool for SIBO by consensus, because they correlate poorly with symptoms and small bowel aspirates and may lead to unnecessary antibiotics. ^[1] The European guideline on hydrogen and methane breath tests remains the reference for how to perform and interpret these tests where they are used. ^[8]

• MR or CT enterography for Crohn disease, stricture, small bowel tumour and fistula.
• Faecal chymotrypsin and 13C-mixed triglyceride breath test for fat malabsorption where available. ^[1]
• Chloride sweat test and CFTR gene testing in young patients with exocrine pancreatic insufficiency and suspected cystic fibrosis. ^[1]
• B12 absorption studies. In outline, the Schilling test measures oral radiolabelled B12 with and without intrinsic factor to distinguish pernicious anaemia (lack of intrinsic factor, corrected by giving intrinsic factor) from ileal disease (not corrected). It is rarely used now; serum B12, anti-intrinsic factor and anti-gastric parietal cell antibodies, and (where needed) methylmalonic acid and homocysteine, are preferred.
• Bile acid malabsorption is assessed by SeHCAT retention or by serum 7-alpha-hydroxy-4-cholesten-3-one (C4) and FGF-19 where available. ^[1]

A flowchart for how to move from symptoms to a labelled cause:

Exocrine pancreatic insufficiency is the commonest premucosal cause. It produces bulky, pale, floating, foul-smelling stools, weight loss, bloating and fat-soluble vitamin deficiency, often in someone with chronic pancreatitis (alcohol-related or genetic), cystic fibrosis, pancreatic surgery, pancreatic cancer or (less commonly) diabetes with pancreatic atrophy. Faecal elastase is the practical screening test, and management is with oral pancreatic enzyme replacement with meals, dosed by lipase units per gram of fat, together with vitamin and mineral replacement and treatment of the underlying disease. ^[1]

Loss of bile salts, whether from cholestasis, chronic cholestatic liver disease, a bile leak or loss of the terminal ileum (where they are reabsorbed), produces fat malabsorption and often watery diarrhoea. Extensive ileal resection causes combined bile salt and B12 loss. Treatment targets the underlying biliary disease and supplements fat-soluble vitamins. In pure bile acid malabsorption, cholestyramine or colesevelam can be used, with monitoring of fat-soluble vitamins.

Whipple disease is a rare, potentially fatal, systemic infection caused by the bacterium Tropheryma whipplei. ^[3]

• Who gets it. Classically a middle-aged man. The early feature is intermittent seronegative arthritis or arthralgia, often with fever, for years before gastrointestinal disease appears. Immunosuppressive treatment given for presumed rheumatic disease can worsen the infection. ^[3]
• Presentation. Weight loss, diarrhoea and steatorrhoea; abdominal pain; lymphadenopathy; anaemia and hypoalbuminaemia. Later, the eyes, heart (endocarditis) and central nervous system are involved; neurological disease carries a poor prognosis. ^[3]
• Diagnosis. Duodenal biopsy shows PAS-positive macrophages, and PCR on tissue confirms Tropheryma whipplei. ^[3]
• Treatment. A commonly used regimen is intravenous ceftriaxone 2 g once daily (or meropenem 1 g three times daily) for 14 days, followed by oral trimethoprim-sulfamethoxazole double-strength twice daily for 12 months. ^[3] Because in-vitro data suggest Tropheryma whipplei is intrinsically resistant to trimethoprim, an alternative supported by culture data is doxycycline 200 mg daily with hydroxychloroquine 600 mg daily for 12 months in classical disease, or 12 to 18 months for localised disease. ^[3] Patients who cannot take ceftriaxone can receive meropenem, and those intolerant of trimethoprim-sulfamethoxazole can receive doxycycline. ^[3] Central nervous system involvement is frequent even without symptoms, so treatment must reach the brain. ^[3] Note that protocols differ between centres; follow local infectious disease guidance.

Tropical sprue is an acquired malabsorption syndrome of presumed infectious cause that occurs in the Caribbean, southern India and Southeast Asia, in both natives and visitors, and usually after at least a month in an endemic area. ^[4] It causes villous atrophy and impaired absorption of folate and vitamin B12. ^[4]

• Presentation. An acute phase of diarrhoea with fever and malaise, followed by chronic milder diarrhoea, nausea, anorexia, cramps, fatigue, steatorrhoea, weight loss, glossitis, stomatitis and peripheral oedema. Megaloblastic anaemia is characteristic. ^[4]
• Diagnosis. Suspect it in anyone who has lived in or visited an endemic area and has malabsorption with megaloblastic anaemia. The test of choice is small bowel biopsy. Unlike coeliac disease, coeliac serology is negative. D-xylose absorption is abnormal in over 90% of cases. ^[4]
• Treatment. Tetracycline (or doxycycline) for up to six months, with folate for the first month and vitamin B12 injections for several weeks; other nutrient replacements as needed. Failure to respond within four weeks suggests another diagnosis, and relapse can occur. ^[4]

Giardia lamblia can cause chronic villous atrophy with bloating, loose and sometimes fatty stools; treat with metronidazole or tinidazole and confirm clearance.

Coeliac disease is an HLA-restricted, gluten-sensitive mucosal enteropathy. It is the commonest cause to look for in malabsorption without an obvious explanation. ^[1] It can be asymptomatic, iron-deficient only, or present with full malabsorption. Management is a strict lifelong gluten-free diet; refractory and complicated forms need specialist care. ^[1]

Bacterial overgrowth occurs when the small bowel, normally relatively sterile, is colonised by coliforms from the colon. It causes bloating, flatulence, variable diarrhoea or constipation, malabsorption of fat-soluble vitamins and B12, and sometimes neuropathy and anaemia. ^[2]

Risk factors include motility disorders, reduced gastric acid, structural abnormalities (strictures, diverticula, surgically altered anatomy), immunodeficiency, Crohn disease, diabetes, systemic sclerosis and chronic opioid or PPI use. ^[2]

Diagnosis relies on objective testing because symptoms are non-specific. Jejunal aspirate with 100,000 or more colony-forming units per millilitre is the traditional gold standard; a duodenal aspirate cut-off of 1,000 colony-forming units per millilitre is now also used. Breath tests are widely used because they are non-invasive; a positive test shows a rise of at least 20 ppm hydrogen, at least 10 ppm methane, or a combined rise of at least 15 ppm within 90 minutes, though both tests have limited accuracy. ^[2] Protozoa or inflammatory bowel overlap mean clinical context matters. ^[2]

Treatment of SIBO. Address the underlying cause and correct vitamin deficits first. Antibiotics are the main treatment. ^[2]

• Rifaximin, a non-absorbable antibiotic, is widely recommended as first-line, 550 mg three times daily for 10 to 14 days. ^[2]
• Systemic alternatives include metronidazole 250 mg three times daily, ciprofloxacin 500 mg twice daily, amoxicillin-clavulanate 875 mg twice daily, doxycycline 100 mg once or twice daily, neomycin, norfloxacin, tetracycline and trimethoprim-sulfamethoxazole. ^[2]
• Recurrence is common, associated with older age, PPI use and altered anatomy; reassess with a breath test before repeating antibiotics. ^[2]
• Probiotics remain controversial; evidence is mixed and they may even produce SIBO in some settings. ^[2]
• A low-FODMAP diet can be used alongside antibiotics, but the strict phase should not continue beyond about six weeks. ^[2]
• Where testing is unavailable, an empiric antibiotic trial may be reasonable in a patient with high clinical suspicion. ^[2]

Short bowel syndrome results from extensive resection of the small intestine, most often from mesenteric ischaemia, Crohn disease, malignancy, trauma or radiation enteritis. It causes loss of macronutrients, micronutrients, water and electrolytes, producing diarrhoea, steatorrhoea, dehydration and malnutrition. Adult incidence is low, around 0.6 to 5 cases per million adults. ^[5]

Anatomy determines severity. Type 1 is an end-jejunostomy with no colon in continuity and is the most severe. Type 2 is a jejunocolic anastomosis with no ileum and has an intermediate prognosis. Type 3 preserves the ileum, colon and ileocaecal valve and has the best chance of weaning from parenteral support. ^[5]

Management is nutritional and rehabilitative. The early goals are stabilisation with parenteral nutrition, transition to enteral and oral feeding, and treatment of high-output losses with anti-diarrhoeals and acid suppression. GLP-2 analogue therapy:

• Teduglutide is a glucagon-like peptide-2 analogue given as a daily subcutaneous injection of 0.05 mg/kg. It stimulates mucosal growth, increases villus height and crypt depth, slows gastric emptying and enhances barrier function, improving absorption and reducing parenteral support needs. ^[5]
• In a randomised trial, 63% of treated patients achieved at least a 20% reduction in parenteral support volume by 24 weeks versus 30% with placebo, and by week 52 about 68% of those on 0.05 mg/kg had a clinically meaningful reduction. ^[5]
• Meta-analysis suggests parenteral support independence in roughly 21% of patients after two years or more. ^[5]
• Indicated only for patients dependent on parenteral support; not for patients who are nutritionally independent. ^[5]
• Common adverse effects are abdominal pain, nausea, vomiting, distension and flatulence. Teduglutide is associated with gastrointestinal polyp formation, so colonoscopy, gastroscopy and abdominal ultrasound are recommended before starting, after one year, and every three to five years thereafter. It is contraindicated in active gastrointestinal malignancy. ^[5]

Radiation enteritis, autoimmune enteropathy, common variable immunodeficiency, eosinophilic enteropathy, mastocytosis, amyloidosis, cyclosporiasis, cryptosporidiosis (especially in immunocompromise) and HIV enteropathy all belong in the differential; each is diagnosed by its clinical and histological setting.

Lactose intolerance is a non-immune, enzymatic problem: too little lactase activity to hydrolyse the lactose in milk and dairy, so undigested lactose reaches the colon, ferments and draws water into the lumen, causing pain, bloating, flatulence and diarrhoea. ^[6] It is the commonest disaccharidase problem and the main cause of milk-related symptoms outside infancy.

Lactase is expressed only in mature enterocytes, located at the villous tips, from at least 34 weeks of gestation. ^[6]

1. Primary (adult-type hypolactasia, lactase non-persistence). Lactase activity falls after weaning, in genetically determined patterns, usually after about one to six years of age depending on ancestry. In primary lactose intolerance intestinal lactase falls to less than 10% of infant levels. It is permanent, slowly progressive and irreversible, and is the normal adult state for most of the world's population. ^[6][8] Children of African, Asian and Latin American ancestry may become symptomatic at two to three years; those of European and North American ancestry more often at five to six years or later. ^[6] Northern Europeans have the lowest prevalence. ^[8]
2. Secondary. Any disease that damages the small bowel mucosa can reduce mature enterocytes and therefore lactase: gastroenteritis (Rotavirus, Norovirus), giardiasis, cryptosporidiosis, coeliac disease, Crohn disease, cystic fibrosis, AIDS, short bowel, bacterial overgrowth, chemotherapy or radiation enteritis, and severe malnutrition. Secondary intolerance is usually reversible once the epithelium heals. ^[6][8]
3. Developmental. Relative lactase deficiency in infants born before about 34 weeks gestation. ^[8]
4. Congenital. A very rare autosomal recessive defect in the lactase (LPH) gene causing severe diarrhoea and dehydration in the neonatal period. ^[6]

The classic picture is abdominal pain, bloating, borborygmi and flatulence soon after lactose ingestion, with watery acidic diarrhoea and anal irritation. Extra-intestinal symptoms such as headache and lethargy are reported in up to one in five people. Severity depends on the dose of lactose relative to residual lactase activity, so many people tolerate small amounts. ^[6]

• Clinical trial. Relief of symptoms on a lactose-free diet followed by recurrence on reintroduction of lactose is a practical, accepted approach. ^[6]
• Hydrogen breath test. Method of choice, with sensitivity of 76 to 100% and specificity of 90 to 100%. A dose of 25 to 50 g of lactose is used to test malabsorption and 25 g to test intolerance; a rise of at least 20 ppm in hydrogen above baseline indicates malabsorption or maldigestion. ^[6][8]
• Genetics. The LCT-13910 C/T polymorphism predicts lactase persistence in Europeans (CC deficiency, TT persistence); other variants operate in other populations. The test predicts predisposition, not current tolerance. ^[8]
• Jejunal biopsy for lactase activity remains the gold standard, but is invasive and mostly a research tool. ^[6]

• Reduce or avoid lactose only when a true diagnosis has been made; keep intake symptom-guided rather than completely lactose-free whenever possible. ^[6]
• Reintroduce lactose after one to two months, once symptoms have settled and lactase has recovered in secondary cases. ^[6]
• Lactase enzyme tablets or drops can be taken with dairy.
• Keep calcium intake adequate during any restriction, through lactose-free dairy, fortified foods or supplements, because calcium and vitamin absorption suffer with the diet. ^[6]
• Treat the underlying cause in secondary intolerance to restore lactase. ^[6]

These are different conditions and are commonly confused. Lactose intolerance is a non-immune carbohydrate-enzyme problem. Cow milk protein allergy is an immune reaction to milk proteins (casein and whey) and can be IgE-mediated, non-IgE-mediated or mixed. ^[6]

• Lactose intolerance causes gastrointestinal symptoms only; cow milk protein allergy can affect the skin (eczema, urticaria) and airways (wheeze, anaphylaxis) as well, can cause rectal bleeding and failure to thrive, and is associated with a family history of atopy. ^[6]
• Cow milk allergy patients tolerate lactose; lactose-intolerant patients tolerate milk proteins. A cow milk allergic child with enteropathy, however, can develop secondary lactase deficiency, so the two can overlap. ^[6]
• Management differs: lactose intolerance is managed by reducing lactose and using lactase enzyme; milk protein allergy requires strict avoidance of cow milk protein, with hydrolysed or amino acid formula in infants. Lactose-free milk still contains cow milk protein and is therefore unsuitable for milk allergy. ^[6]
• Notably, primary lactose intolerance is uncommon in infants; a clinician who labels an infant's milk reaction as lactose intolerance should first consider cow milk protein allergy. ^[6]

Untreated or severe malabsorption leads to:

• Macronutrient deficiency: protein-energy malnutrition, low albumin, oedema, loss of muscle and fat.
• Vitamin and mineral deficiency with their specific consequences (see the table above and the Key points).
• Anaemia: iron deficiency, folate or B12 deficiency, sometimes both; osteopenia or osteomalacia and fracture.
• Electrolyte disturbance, dehydration, kidney stones from hyperoxaluria.
• In short bowel: intestinal failure, central venous catheter complications, liver disease from long-term parenteral nutrition, metabolic bone disease.
• In coeliac disease: refractory disease, ulcerative jejunoileitis, small bowel lymphoma (rare).

Prognosis depends entirely on the cause. Coeliac disease usually resolves on a gluten-free diet. Exocrine pancreatic insufficiency is controlled with enzymes and nutrition. SIBO and tropical sprue respond to antibiotics. Whipple disease is curable but relapses and central nervous system disease worsen outlook. Short bowel carries chronic intestinal failure but gradual intestinal adaptation, plus teduglutide in selected patients, improves absorption over months to years.

There is no population screening for malabsorption as a whole. Coeliac disease screening is appropriate in high-risk groups and in anyone with malabsorption of no obvious cause. ^[1] Galactosaemia and other congenital disorders are picked up on newborn screening. For milk-related symptoms in infants, distinguishing lactose intolerance from cow milk protein allergy early prevents both missed treatment and unnecessary restriction.

• Pregnancy. Deficiencies of folate and iron are common and dangerous; treat promptly. Tropical sprue and coeliac disease can first present or worsen in pregnancy.
• Children. Coeliac disease, cystic fibrosis and congenital enteropathies present with failure to thrive. Tropical sprue occurs in children. Secondary lactose intolerance after gastroenteritis is common in children under two.
• Older adults. Check for pancreatic cancer, mesenteric ischaemia and malabsorptive drug effects; B12 deficiency from atrophic gastritis is common.
• Immunocompromised. Opportunistic infections (giardiasis, cryptosporidiosis, CMV), bacterial overgrowth and HIV enteropathy are more likely; antibiotic and antiretroviral treatment matters.

In many low- and middle-income countries, children are exposed to repeated enteric pathogens through poor water and sanitation, producing an acquired enteropathy called environmental enteric dysfunction (EED): villous blunting, crypt hyperplasia, inflammation and increased permeability. It presents not as acute diarrhoea but as subclinical malabsorption, poor growth (stunting and wasting) and reduced vaccine response. ^[7]

EED has no universal case definition or easily available test; endoscopic biopsy is the gold standard, which is why the diagnosis is usually made by proxy in research settings. ^[7] Water, sanitation and hygiene interventions at household level have had limited effect on growth or EED in trials, so efforts now focus on treatment approaches for those at highest risk, on improving nutrition and on preventing repeated infection. ^[7] Clinically, in a low-resource setting, persistent suboptimal growth in a child with a reasonable diet should raise EED together with other treatable causes of malabsorption.

• Malabsorption is failure of nutrient uptake; maldigestion is failure of breakdown. Clinically they are managed together. ^[1]
• Physiologically, fat and fat-soluble vitamins are absorbed in the proximal jejunum, protein in the jejunum, carbohydrate in the duodenum and jejunum, iron and calcium in the duodenum, folate in the jejunum, and vitamin B12 in the terminal ileum. Unabsorbed carbohydrate is salvaged by the colon. ^[1]
• Causes group as premucosal, mucosal, and transport. The history, examination and baseline bloods generate the differential before any invasive test. ^[1]
• Coeliac disease must be excluded in anyone with malabsorption and no obvious explanation. ^[1]
• Faecal elastase under 100 microg/g supports exocrine pancreatic insufficiency; 100 to 200 microg/g is indeterminate. ^[1]
• Whipple disease is a rare systemic infection with PAS-positive macrophages and Tropheryma whipplei PCR on duodenal biopsy; classically a middle-aged man with prior seronegative arthritis. It is treated with ceftriaxone then trimethoprim-sulfamethoxazole, or doxycycline plus hydroxychloroquine where appropriate. ^[3]
• Tropical sprue occurs in tropical regions, causes megaloblastic anaemia, shows negative coeliac serology, and improves with tetracycline for up to six months plus folate and B12. ^[4]
• SIBO is diagnosed by high jejunal aspirate counts (100,000 colony-forming units per millilitre or more) and treated first-line with rifaximin 550 mg three times daily for 10 to 14 days. ^[2]
• Short bowel is managed with parenteral support, adaptation and, in dependent patients, teduglutide 0.05 mg/kg daily, which grows mucosa and can reduce parenteral needs; it requires polyp surveillance. ^[5]
• Lactose intolerance is an enzyme problem, not an allergy; reduce lactose symptom-guided, use lactase enzyme when needed, and protect calcium intake. ^[6]
• Lactose breath testing uses 25 to 50 g lactose with a 20 ppm hydrogen cut-off for malabsorption. ^[6][8]
• Cow milk protein allergy is immune-mediated, can cause skin and respiratory symptoms and anaphylaxis, and is managed by strict protein avoidance, not lactose restriction. ^[6]
• Environmental enteric dysfunction is an acquired, subclinical, enteropathy of children in low-resource settings, linked to poor sanitation, villous blunting, poor growth and poorer vaccine responses. ^[7]

• Coeliac disease
• Chronic pancreatitis
• Cystic fibrosis
• Crohn disease
• Giardiasis
• Gastroenteritis and HIV enteropathy
• Inflammatory bowel disease
• Short bowel and intestinal failure
• Lactose and other carbohydrate intolerances
• Anaemia, B12 and folate deficiency
• Malnutrition in children
• Environmental enteric dysfunction
• Nutritional support and parenteral nutrition
• Gastrointestinal endoscopy and small bowel biopsy