Digestive Diseases

TL;DR. The digestive tract is a nine-metre tube that is technically outside the body: a hostile chemical processing line, staffed by trillions of bacteria, with its own nervous system containing more neurons than the spinal cord. Most of what goes wrong with it falls into four groups. Things that should stay down come up (reflux). The lining gets digested by the acid it is supposed to contain (peptic ulcer, which turned out to be an infection). Something solid forms where it should not (gallstones, diverticula). Or the tube works badly with no visible damage at all (irritable bowel syndrome), which is the commonest of the lot and the one most often dismissed. The single most important story here is the discovery that a bacterium causes stomach ulcers, which took a physician deliberately drinking a culture of it to be believed.

Key takeaways

• Peptic ulcers are mostly an infection. Helicobacter pylori causes the majority, and a one-week course of antibiotics cures a disease that was previously managed with lifelong drugs and surgery.
• Barry Marshall drank a culture of H. pylori in 1984 to prove it caused gastritis. He and Robin Warren received the Nobel Prize in 2005.
• Irritable bowel syndrome affects roughly 4 to 10 percent of people worldwide, has a real mechanism (disordered gut-brain signalling and visceral hypersensitivity), and is not a diagnosis of exclusion by default.
• Reflux causing Barrett's oesophagus is the precursor to a cancer that has risen sharply in Western countries.
• Proton pump inhibitors are extremely effective and extremely overused, frequently continued for years without review.
• Blood in the stool, unexplained weight loss, difficulty swallowing, persistent vomiting, and anaemia are never to be put down to a functional disorder without investigation.

The tube, briefly

Food passes through: mouth, oesophagus, stomach (acid at pH 1.5 to 3.5, plus pepsin, which begins protein digestion), small intestine (where nearly all absorption happens, over a surface area of about 30 square metres of villi, aided by bile from the liver and enzymes from the pancreas), and colon (which reclaims water and hosts the microbiome).

Two features matter for what follows. The lower oesophageal sphincter is a muscular valve that keeps acid where it belongs. And the stomach lining protects itself from its own acid with a mucus and bicarbonate layer maintained by prostaglandins, which is exactly the pathway NSAIDs block, and therefore why they cause ulcers.

Gastro-oesophageal reflux disease (GORD/GERD)

In short: Acid where the lining has no protection, and its long-term consequence is a cellular change that precedes a rising cancer.

What it is. Stomach contents refluxing into the oesophagus often enough to cause symptoms or damage. The oesophageal lining has no protection against acid, so exposure causes the burning sensation of heartburn.

What goes wrong. Transient relaxations of the lower oesophageal sphincter, sometimes with a hiatus hernia (part of the stomach sliding up through the diaphragm, removing the diaphragm's supporting pinch). Contributors: obesity (raised abdominal pressure), pregnancy, large or late meals, alcohol, smoking, and drugs that relax the sphincter.

What it does. Heartburn and acid regurgitation, worse lying flat or bending. Also less obvious presentations: chronic cough, hoarseness, sore throat, dental erosion, and non-cardiac chest pain (which must be distinguished from cardiac pain, and the distinction cannot be made confidently on symptoms alone). Complications: oesophagitis, ulceration, stricture, and Barrett's oesophagus.

Barrett's oesophagus is the important one. Under chronic acid exposure, the squamous lining of the lower oesophagus is replaced by a more acid-resistant intestinal-type lining (metaplasia). That adaptation is itself premalignant: Barrett's carries an increased risk of oesophageal adenocarcinoma, a cancer that has risen several-fold in Western countries over recent decades in parallel with obesity. Absolute annual progression risk is low (roughly 0.1 to 0.5 percent per year), so most people with Barrett's never develop cancer, and surveillance endoscopy is offered to detect dysplasia, which can now be treated by endoscopic radiofrequency ablation rather than oesophagectomy.

Treatment. Weight loss where relevant, raising the head of the bed, avoiding late meals, stopping smoking, and identifying individual trigger foods. Proton pump inhibitors (omeprazole, lansoprazole) irreversibly block the stomach's acid pump, the final common step in acid secretion, and are highly effective. Surgery (fundoplication, wrapping the top of the stomach around the lower oesophagus) for selected patients.

Alarm features requiring endoscopy rather than empirical treatment: difficulty or pain on swallowing, weight loss, vomiting, anaemia, a palpable mass, and new symptoms over the age of 50 to 55.

Peptic ulcer disease, and the best story in modern medicine

In short: A physician drank a culture of the bacterium in 1984 to prove it caused ulcers, and a chronic disease became a one-week antibiotic course.

What it is. A break in the lining of the stomach or duodenum extending through the muscularis mucosae, caused by an imbalance between acid and mucosal defence.

The history. For most of the twentieth century, ulcers were understood as a disease of stress and acid, treated with bland diets, milk, antacids, acid-suppressing drugs, and, when those failed, surgery to cut the vagus nerve or remove part of the stomach. The idea that bacteria could live in the stomach was considered absurd: nothing survives pH 1.5.

In 1982, Robin Warren, a pathologist in Perth, noticed curved bacteria in stomach biopsies and, with Barry Marshall, cultured them (by accident, after a plate was left over an Easter weekend for five days rather than the standard two). They proposed the organism caused gastritis and ulcers, and were widely dismissed.

In 1984, unable to produce disease in animal models and unable to persuade reviewers, Marshall drank a broth culture of the organism. He developed gastritis within days, documented by biopsy, and cured himself with antibiotics. It took another decade for practice to change fully. They received the Nobel Prize in Physiology or Medicine in 2005.

The result: peptic ulcer disease was reclassified from a chronic condition managed for life into an infection cured in a week. Ulcer surgery, once a large part of general surgical practice, essentially disappeared. It is the clearest recent example of a whole disease category being rewritten, and of how strongly a plausible existing model can resist evidence.

What actually goes wrong. H. pylori survives the stomach by producing urease, which splits urea into ammonia and carbon dioxide, creating an alkaline cloud around itself, and by burrowing into the mucus layer. It provokes chronic inflammation, which alters acid secretion and weakens mucosal defence. Roughly half the world's population is infected, most without symptoms; a minority develop ulcers, and a smaller minority develop gastric cancer or gastric MALT lymphoma, which can regress on eradicating the bacterium alone.

The other major cause is NSAIDs, which block COX-1 and therefore the prostaglandins that maintain the protective mucus and bicarbonate layer. Aspirin, ibuprofen, naproxen, and diclofenac all do this, and the risk rises with age, dose, duration, and concurrent steroids or anticoagulants.

What it does. Burning epigastric pain, classically relieved by food in duodenal ulcer and worsened by it in gastric ulcer, though the distinction is unreliable. Complications: bleeding (which can present as vomiting blood or as black tarry stools, and which is a common cause of emergency admission), perforation (sudden severe pain and a rigid abdomen, a surgical emergency), and gastric outlet obstruction.

Treatment. Test for H. pylori (urea breath test, stool antigen, or biopsy) and eradicate it with a proton pump inhibitor plus two or three antibiotics for 7 to 14 days, with regimens now varying by local clarithromycin resistance. Stop NSAIDs where possible, or co-prescribe a proton pump inhibitor where they are essential. Confirm eradication afterwards.

Irritable bowel syndrome

In short: A real disorder of gut-brain signalling with measurable abnormalities, not an absence of disease, and it has more effective treatments than its reputation suggests.

What it is. Recurrent abdominal pain associated with defecation or with a change in stool frequency or form, in the absence of structural disease. Subtyped by predominant stool pattern (IBS-D diarrhoea, IBS-C constipation, IBS-M mixed).

What actually goes wrong. IBS is a disorder of gut-brain interaction, and calling it that rather than "functional" is a deliberate change in terminology reflecting a real mechanism:

• Visceral hypersensitivity: the same degree of gut distension produces pain at lower thresholds, demonstrable experimentally with balloon distension studies.
• Altered motility, both too fast and too slow.
• Post-infectious onset in a substantial minority: roughly 10 percent of people develop IBS after a bout of bacterial gastroenteritis, which is among the strongest pieces of evidence that something real happens to the gut.
• Low-grade immune activation and increased intestinal permeability in some patients.
• Microbiome differences, associations rather than proven causes.
• Central processing: brain imaging shows altered pain processing, and stress, anxiety, and early adverse experience are strongly associated. This is bidirectional rather than a claim that the condition is psychological.

What it does. Pain, bloating, urgency, incomplete evacuation, and a substantial impact on quality of life, work, and social activity. It does not cause weight loss, bleeding, anaemia, or night-waking pain, and any of those means the diagnosis is wrong and needs investigation.

Who gets it. Roughly 4 to 10 percent of adults using current criteria, about twice as common in women, typically starting before 50.

Treatment, which has more evidence behind it than its reputation suggests:

• Diet: soluble fibre (ispaghula) for constipation-predominant disease; a low-FODMAP diet (restricting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which are poorly absorbed carbohydrates that draw water into the bowel and are fermented to gas) helps roughly half to three-quarters of patients in trials. It should be dietitian-supervised and followed by systematic reintroduction, because long-term restriction damages the microbiome and nutrition.
• Antispasmodics (mebeverine, peppermint oil) for pain.
• Loperamide for diarrhoea; laxatives, linaclotide, or prucalopride for constipation.
• Low-dose tricyclic antidepressants, which act on gut motility and on pain signalling at doses far below antidepressant doses. A large trial confirmed amitriptyline's benefit in primary care.
• Gut-directed psychological therapies, including cognitive behavioural therapy and gut-directed hypnotherapy, which has surprisingly good trial evidence and is under-provided.
• Rifaximin, a poorly absorbed antibiotic, for diarrhoea-predominant disease.

Exclude coeliac disease (Chapter 47) before settling on IBS, since it is common, treatable, and presents identically. Faecal calprotectin distinguishes IBS from inflammatory bowel disease inexpensively.

Gallstones

In short: Usually silent, and dangerous only when a stone obstructs something, which it can do in five distinct and increasingly serious ways.

What it is. Stones formed in the gallbladder, mostly of cholesterol, which precipitates when bile is supersaturated with it relative to bile salts and phospholipids.

Who gets them. The classic teaching mnemonic (female, forty, fertile, fat, fair) is crude and directionally correct: risk factors are female sex, pregnancy, obesity, rapid weight loss (including after bariatric surgery, which is why prophylactic drugs are sometimes given), age, family history, and certain ethnicities, with very high rates in some Indigenous populations of the Americas. Around 10 to 15 percent of adults in Western countries have gallstones, and most never know.

What they do. Most are silent. Problems arise when a stone obstructs something:

Treatment. Laparoscopic cholecystectomy for symptomatic stones, one of the commonest operations performed. Silent stones are generally left alone. ERCP (endoscopic retrograde cholangiopancreatography) to remove duct stones.

Pancreatitis

Acute pancreatitis is the pancreas digesting itself: enzymes activate inside the gland instead of in the intestine. The two dominant causes are gallstones and alcohol, together accounting for the majority; others include high triglycerides, drugs, and ERCP.

It causes severe upper abdominal pain radiating to the back, vomiting, and, in severe cases, systemic inflammatory response, organ failure, and death, with overall mortality of a few percent rising sharply in severe necrotising disease. Treatment is supportive: fluids, analgesia, early enteral nutrition (which has replaced the old practice of prolonged starvation), and treatment of the cause, including early cholecystectomy in gallstone pancreatitis to prevent recurrence.

Chronic pancreatitis, usually from prolonged alcohol use, destroys the gland progressively, producing chronic pain, malabsorption with fatty stools requiring enzyme replacement, and diabetes.

Diverticular disease

Diverticula are small pouches of mucosa herniating through weak points in the colon wall where blood vessels penetrate. They form under raised intraluminal pressure and are extremely common in Western populations over 60, and much less common in populations with high-fibre diets, which is the basis of the traditional low-fibre explanation, though the evidence is more mixed than the textbooks once suggested.

Most people have them and never know (diverticulosis). Diverticulitis is inflammation or micro-perforation of a diverticulum, causing left lower abdominal pain, fever, and altered bowel habit, and it can progress to abscess, perforation, fistula, or stricture. Uncomplicated diverticulitis is increasingly managed without antibiotics in selected patients, a reversal of long practice supported by randomised trials. Diverticula can also bleed, sometimes heavily.

The old advice to avoid nuts, seeds, and popcorn has been refuted by prospective cohort data showing no increased risk, and in fact an inverse association.

Constipation and haemorrhoids

Constipation is extremely common, more so in women, older people, and in those on opioids, anticholinergics, iron, and calcium channel blockers. Management: fluid, fibre (increased gradually, since a sudden increase causes bloating), physical activity, bulk-forming then osmotic then stimulant laxatives in sequence, and specific agents for opioid-induced constipation that block peripheral opioid receptors in the gut without reversing analgesia.

Haemorrhoids are enlarged vascular cushions in the anal canal, present in everyone and symptomatic when they enlarge, prolapse, or bleed. They cause bright red rectal bleeding, itching, and discomfort. The essential clinical point: rectal bleeding must not be assumed to be haemorrhoids, particularly over 40 or with any change in bowel habit, because colorectal cancer presents the same way and the assumption delays diagnosis routinely.

What the person can do

In short: Know the alarm symptoms, test for coeliac disease before removing gluten, and review long-term acid suppression.

• Know the alarm symptoms. Difficulty swallowing, unintentional weight loss, persistent vomiting, blood in vomit or stool, black tarry stools, iron-deficiency anaemia, a palpable mass, and new persistent symptoms after 50. None of these belongs to a functional diagnosis until investigated.
• Get tested for coeliac disease before removing gluten, not after, since testing requires gluten in the diet.
• Review long-term proton pump inhibitors. They are effective and appropriate for many indications and are frequently continued for years without a reason. Long-term use is associated with modestly increased risks of enteric infection including C. difficile, low magnesium and B12, and fracture. Stopping abruptly after long use causes rebound acid hypersecretion, so tapering helps.
• Use NSAIDs carefully, especially over 60, with a history of ulcer, or alongside steroids or anticoagulants. Ask whether gastric protection is needed.
• Take up bowel cancer screening when offered (Chapter 25). This is the highest-value action in this chapter.
• For reflux: lose weight if relevant, avoid eating within three hours of lying down, raise the head of the bed rather than piling up pillows, and stop smoking.
• For IBS: seek a positive diagnosis rather than an indefinite search, try structured interventions (dietitian-supervised low-FODMAP, gut-directed hypnotherapy, low-dose amitriptyline) rather than serial elimination diets, and treat co-existing anxiety, which improves gut symptoms through a real physiological route.
• Be sceptical about "leaky gut," food intolerance test panels, candida overgrowth diagnoses, and colonic irrigation. Intestinal permeability is a real measurable phenomenon and the commercial edifice built on it is not supported by evidence, and the accompanying restrictive diets and supplements cause real cost and occasional harm.

Living with it

Digestive symptoms are embarrassing, which delays presentation, and functional disorders are frequently dismissed, which is both unkind and clinically wrong given the evidence base that now exists for treating them. Patients with IBS commonly report being told there is "nothing wrong," which is a misstatement: what they have is a disorder of gut-brain signalling with measurable abnormalities, not an absence of disease.

At the same time, the direction of error runs both ways. People with genuinely alarming symptoms attribute them to stress or to haemorrhoids and wait months, and colorectal cancer in particular is frequently diagnosed later than it should be for exactly that reason.

What's next

• Non-endoscopic Barrett's screening, using swallowable sponge devices that collect cells from the oesophagus, which could identify who needs endoscopy at a fraction of the cost.
• Microbiome-based therapy, currently proven only for recurrent C. difficile and heavily oversold everywhere else.
• Better IBS subtyping, including bile acid malabsorption and post-infectious phenotypes, which respond to specific treatments and are frequently missed.
• H. pylori eradication as gastric cancer prevention, with population screening and treatment programmes in high-incidence countries showing reductions in gastric cancer incidence, balanced against antibiotic resistance concerns.
• Artificial intelligence in endoscopy, which improves adenoma detection rates during colonoscopy and is already in routine use in some centres.

Sources and notes

H. pylori discovery: Warren and Marshall, The Lancet, 1983; Marshall's self-experiment, Medical Journal of Australia, 1985; Nobel Prize 2005. IBS prevalence: Rome Foundation global epidemiology study, Sperber et al., Gastroenterology, 2021 (about 4 percent by Rome IV criteria, higher by earlier criteria). Post-infectious IBS: Klem et al., meta-analysis, 2017. Low-FODMAP diet: multiple randomised trials and Monash University's research programme. Amitriptyline in IBS: ATLANTIS trial, The Lancet, 2023. Gut-directed hypnotherapy: systematic reviews. Barrett's progression risk: Hvid-Jensen et al., NEJM, 2011. Nuts and seeds in diverticular disease: Strate et al., JAMA, 2008. Antibiotics in uncomplicated diverticulitis: AVOD and DIABOLO trials. Proton pump inhibitor long-term safety: observational associations of uncertain causality, reviewed in Gastroenterology. H. pylori prevalence: roughly half the world's population, per global meta-analyses.

Open questions. Whether microbiome manipulation can treat IBS is unproven. Whether long-term proton pump inhibitor associations are causal is unresolved. Which patients with Barrett's oesophagus will progress cannot yet be predicted well enough to target surveillance.

Next: the conditions this book has referred to repeatedly without ever explaining them, starting with the commonest blood disorder on earth. 👉