Digestive enzymes from mouth to colon: who breaks down what

Saliva, stomach, pancreas, gut wall and bacteria each contribute their own enzymes. A map of where each enzyme works, and what happens when one is missing.

How solid is the research? Well supported

Where each enzyme works is very well researched. Lactase and pancreatic enzyme replacement are also well supported. For most over-the-counter enzyme blends, by contrast, there is hardly any evidence.

Cause or consequence? Cause and consequence

If you make too few enzymes, you break down sugar and fat less well. This explains symptoms and nutrient deficiency.

Healthy state

Enzymes are proteins that break food down into building blocks the gut can absorb: starch into sugar, protein into amino acids, fat into fatty acids. Each enzyme fits only certain bonds. That is why a whole range of them is needed, in different places.

In the mouth, salivary amylase starts on the starch. How much of it someone makes depends on the number of gene copies: people from population groups with a traditionally starch-rich diet have on average more copies and more amylase in their saliva. The stomach makes pepsin, which starts cutting protein, and its own lipase. In a study of healthy people, gastric lipase handled about one in four to one in six of the fat-splitting steps, the pancreas the rest.

The pancreas is the main laboratory. It supplies amylase for starch, lipase for fat, trypsin, chymotrypsin and other proteases for protein, and enzymes for genetic material from food. The lipase needs the Bile acids Substances made by the liver that make fat digestible. About 95 percent are reabsorbed in the last part of the small intestine; gut bacteria transform the rest. More in the chapter “Bile acids: when bile causes diarrhoea”, which break fat up into fine droplets.

The gut wall itself takes the last step. On the tiny projections of the small intestine cells, the brush border, sit enzymes that split double sugars and short protein pieces right before absorption: lactase for milk sugar, sucrase-isomaltase for table sugar and starch remnants, maltase and peptidases. The cells even release small vesicles containing these enzymes, which keep working in front of the surface.

What is left reaches the large intestine and the bacteria. Their genetic material contains a huge variety of enzymes for complex carbohydrates, far more than the human genome. They break down fibre, resistant starch and mucus and turn them into Short-chain fatty acids Acids such as acetate, propionate and butyrate that gut bacteria make from fibre. They nourish the gut wall and act throughout the body. More in the chapter “Butyrate and other short-chain fatty acids”. Bacteria also convert bile acids and break down plant compounds. Humans have outsourced part of their digestion to them.

For enzymes to work, conditions have to be right. Each has its preferred pH: pepsin needs the acidic gastric juice, whereas pancreatic enzymes need an almost neutral environment, which the bicarbonate in pancreatic juice creates. Mixing matters too. Chewing and the kneading movements of the stomach bring enzymes and food together, and the time food stays decides how long there is to split it. That is why acid, motility and enzymes work together, and one enzyme rarely explains a problem on its own.

Each station has its enzymes: mouth, stomach, pancreas, gut wall. Bacteria in the colon break down what is left.

Disrupted state: causes and effects

If a brush border enzyme is missing, the matching sugar slips undigested into the large intestine, where it is fermented and causes gas, bloating and diarrhoea. The best known is lactase deficiency, which is normal in most adults worldwide.

Sucrase-isomaltase is less well known. A complete inborn deficiency is rare. But gene variants that weaken the enzyme were more common in people with Irritable bowel syndrome Recurring abdominal pain linked to bowel movements, without tests finding another cause. Today it is understood as a disorder of gut–brain interaction. More in the chapter “The gut-brain axis”, especially with diarrhoea. One common variant reduced enzyme activity in the lab by 35 per cent. So in some people with IBS, table sugar or starch could play a role.

Some carbohydrates humans fundamentally cannot split, such as the galactans from beans, lentils and cabbage. Humans lack the enzyme alpha-galactosidase for this. They are always fermented by bacteria, which explains the familiar bloating after legumes.

In pancreatic insufficiency, the main enzymes are missing. Fat is poorly digested, stools become greasy, and fat-soluble vitamins are lacking. With a larger bile acid loss, lipase works less well because the fine distribution of fat is missing. After gallbladder removal, by contrast, bile is enough for most people; some only tolerate large, very fatty meals less well.

And if the bacteria are missing, for example after antibiotics, fibre remains unfermented and the production of short-chain fatty acids falls. Conversely, bacteria that are too numerous in the small intestine ferment food too early and cause bloating shortly after eating.

An enzyme deficiency is not always inborn or permanent. After a gastrointestinal infection, with untreated Coeliac disease An autoimmune disease in which gluten damages the lining of the small intestine. It is diagnosed with a blood test and usually a biopsy while you are still eating gluten. More in the chapter “Lactose, fructose, gluten: making sense of intolerances” or in Crohn’s disease, the brush border is damaged, and lactase is often the first to go (secondary lactase deficiency). When the lining heals, it often returns. Whether lactase deficiency causes symptoms also depends on the amount, what is eaten with it and the gut bacteria. People often report tolerating more with regular small amounts, probably because the bacteria adapt. For symptoms, though, this is not established in every case.

If an enzyme at the gut wall is missing, the sugar slips on undigested. In the colon it is fermented: gas and diarrhoea.

Where it comes from and where it leads

The same symptoms can have different roots. This map shows what may be involved in this problem and what may follow from it.

Possible causes
This problem
Possible consequences

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Move the mouse over a box: its connections are highlighted and everything else steps back.

Tap a box to highlight its connections. Tap it again to open the chapter.

Connections, not certainty: a link means “can”, not “must”. What applies to you is best clarified in a talk with your doctor.

What often helps

Lifestyle

Diet, exercise, sleep, social contact and dealing with stress.

Chew thoroughly Chewing breaks food up and gives salivary amylase time. Small bites and thorough chewing take the load off the later stations. This has hardly been studied directly for symptoms, but it does no harm. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [1]
Dose milk sugar instead of avoiding it Most people with lactase deficiency tolerate about 12 g of lactose, roughly a glass of milk, without notable symptoms, especially with a meal. Hard cheese and yoghurt contain less lactose. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [2]
Build up legumes slowly If you rarely eat legumes, you notice them strongly. Small portions, well soaked and cooked, raised in small steps, give the gut bacteria time to adjust. This is plausible and often reported, but not well studied. If legumes cause strong symptoms, a FODMAP issue may also be behind it, see low-FODMAP. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Match triggers to an enzyme Write down after which sugars or starches the symptoms come: milk, table sugar, legumes or bread. Each pattern points to a different enzyme, and the list helps in the doctor’s office. A diary does not replace a test, but it narrows things down. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

Natural supplements

Supplements do not replace a medical check-up. Discuss dosage and interactions with your doctor or pharmacist.

Alpha-galactosidase with legumes In a study of 8 healthy people, the enzyme taken with a bean meal reduced gas production and bloating. It only helps with galactans, that is legumes and cabbage, not with other FODMAPs. Lactase tablets, correspondingly, only work on milk sugar. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [3]
Gluten enzymes do not protect in coeliac disease In a study of 18 gluten-sensitive people, an enzyme from Aspergillus niger broke down most of 0.5 g of gluten while still in the stomach. That is a small amount, and in coeliac disease partial breakdown is not enough. If you have coeliac disease, stay on a strict gluten-free diet. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [4]
Broad-spectrum enzyme blends Over-the-counter blends of plant and fungal enzymes are advertised against fullness. Without proven pancreatic insufficiency, there are no good studies for them. In genuine insufficiency, the prescription pancreatic enzymes are dosed much higher. Over-the-counter blends do not replace them; the dose is adjusted to meals by a doctor. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [5]

Medical treatments

Information, not a treatment recommendation. Decide together with a doctor. Approval and availability differ from country to country.

Consider sucrase-isomaltase deficiency With diarrhoea and bloating after sugar and starch, especially since childhood or running in the family, a deficiency may be behind it. Options are a breath test with sucrose, a genetic test or an enzyme measurement in a small intestine biopsy. How available these tests are varies by country. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [6]
Check the pancreas with greasy stools The elastase test in stool shows whether the pancreas makes enough enzymes. In case of deficiency, enzyme capsules with every meal, adjusted to the fat content, are the standard treatment. Established How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [5]
Breath test if a sugar intolerance is suspected A hydrogen breath test after milk sugar (or other sugars) can measure whether a sugar is fermented in the large intestine. It is the usual test when lactose deficiency is suspected and the basis for targeted rather than blanket avoidance. How well available it is depends on the country. Well supported How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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How we rate the evidence

Trust score 5 of 5:Established: Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies.
Trust score 4 of 5:Well supported: Several randomised studies in humans with largely consistent results.
Trust score 3 of 5:Promising: Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies.
Trust score 2 of 5:Plausible: Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms.
Trust score 1 of 5:Experimental: Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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