Autism and Chronic Gut Symptoms: Could CSID Be the Missing Piece?

There is a particular frustration that comes with living for years in a body that never feels quite right.

Bloating after meals. Abdominal pain that seems impossible to predict. Diarrhoea so intrusive that time spent on the toilet can mean missing school, work, social events, and ordinary moments of life.

Studies show that people with autism spectrum disorder (ASD), in contrast to comparison groups, experienced significantly more general GI symptoms, including higher rates of diarrhoea, constipation, and abdominal pain (McElhanon et al., 2014).

Often these symptoms get filed away as something functional, anxiety-related, or simply part of life with autism — and for those who do get further workup, "IBS" becomes the catch-all label when nothing else explains it.

Over time, people adapt. They start avoiding foods. They trial different fad diets. For many, the search for an explanation quietly comes to an end and they accept pain as normal.

But what if those chronic digestive symptoms have a more specific explanation?

Emerging research suggests that, for a subset of people, an under-recognised digestive enzyme deficiency may be contributing to these symptoms.

The condition is called Congenital Sucrase-Isomaltase Deficiency (CSID).

Rather than a "sensitive gut", the problem may simply be the inability to digest one of the most common components of the modern diet.

What is CSID?

CSID is a genetic digestive enzyme disorder caused by variants in the sucrase-isomaltase (SI) gene. These variants reduce the activity of sucrase-isomaltase, the enzyme needed to digest sucrose and starch-derived carbohydrates.

Sucrase-isomaltase (SI) is an enzyme complex that sits on the brush border of the small intestine. Its role is to digest sucrose (table sugar) and help break down starch-derived carbohydrates into smaller sugars that can be absorbed.

When SI activity is significantly reduced, those carbohydrates remain undigested.

Instead of being absorbed in the small intestine, they draw water into the bowel, which can contribute to diarrhoea, before passing into the large intestine where gut bacteria rapidly ferment them. The result can be bloating, cramping, abdominal pain, excessive gas and diarrhoea. Symptoms that often look almost identical to IBS.

How CSID may contribute to chronic gut symptoms in some people on the spectrum.

For decades, CSID was considered a rare childhood disorder that became obvious as soon as sugary foods were introduced during infancy. Children were often described as presenting with severe diarrhoea and failure to thrive.

We now know the picture is much more complicated.

Some people develop severe symptoms early in life. Others develop milder symptoms that go unrecognised until adolescence or adulthood. Some spend years collecting diagnoses such as IBS, lactose intolerance, "food sensitivities," or functional gastrointestinal disorders before anyone considers that they may not be digesting sucrose and starch properly.

One of the biggest shifts in our understanding of CSID has been the recognition that you do not necessarily need two faulty copies of the SI gene to develop symptoms.

Historically, people carrying a single pathogenic variant were often considered unaffected carriers. Increasing evidence suggests this assumption was too simplistic. For some people, having only one working copy of the SI gene may reduce enzyme activity enough to cause symptoms, particularly when dietary sucrose and starch intake exceeds their digestive capacity.

In addition, some SI variants appear to have a dominant-negative effect. In these cases, the altered enzyme does more than simply fail to work. It can interfere with the normal enzyme made from the other copy of the gene, further reducing overall sucrase-isomaltase activity. This may help explain why some people with only one identified SI variant can have symptoms that are much more severe than expected.

In practical terms, CSID is not always a simple “two faulty copies or no disease” condition. There appears to be a spectrum, ranging from milder symptoms in some carriers to more severe disease when enzyme activity is profoundly reduced.

So what does this have to do with autism?

Why CSID may be missed in people on the spectrum

Children and adults with ASD are more likely to experience chronic gastrointestinal symptoms, but those symptoms are not always investigated in depth. There are several reasons for this.

Some people on the spectrum may communicate pain differently. Some may have difficulty identifying or describing internal body sensations — differences in interoception, the ability to sense and interpret signals from inside the body. Others may express digestive discomfort through changes in behaviour, sleep, appetite, anxiety, irritability or food refusal.

This can make it easier for gut symptoms to be misattributed to autism itself, sensory sensitivities, anxiety, “picky eating,” or behavioural issues.

But digestive symptoms should not automatically be explained by autism alone. A person on the spectrum can also have coeliac disease, inflammatory bowel disease, lactose intolerance, food allergies, constipation, reflux — or a digestive enzyme deficiency such as CSID.

The risk is that once symptoms are explained as “just autism” or “just IBS,” the search for treatable causes may stop too soon.

The research connecting CSID and autism

Chronic gastrointestinal symptoms are common in people on the spectrum, and some of those symptoms are exactly the kind seen when carbohydrates are not properly digested — bloating, abdominal pain, diarrhoea and excessive gas, which can all occur when sugars and starch-derived carbohydrates remain undigested in the gut.

That overlap makes it reasonable to ask whether digestive enzyme deficiencies may be missed in some people on the spectrum with long-standing food-related symptoms.

The idea that digestive enzyme deficiencies might contribute to gastrointestinal symptoms in autism is not new. In 2011, researchers at Harvard measured disaccharidase activity in duodenal biopsy samples from 199 people diagnosed with ASD undergoing endoscopy for gastrointestinal symptoms. Kushak and colleagues assessed lactase, sucrase and maltase activity.

The findings were striking:

Lactase deficiency was the most common finding, affecting 62% of the group. But sucrase deficiency was also found in 16% of participants, and maltase deficiency in 10%.

Perhaps even more important was what the biopsies did not show.

Most participants did not have visible inflammation or obvious intestinal damage. In fact, 94% had normal duodenal histology, while only 6% had mucosal inflammation.

This highlights an important clinical point: a routine biopsy can look entirely normal under the microscope while significant digestive enzyme deficiencies remain hidden.

Unless disaccharidase activity is measured specifically, the diagnosis can easily be missed.

Fourteen years later, researchers asked the next logical question.

If reduced sucrase activity can be found in some people on the spectrum with chronic gastrointestinal symptoms, how many might actually carry clinically relevant variants in the SI gene?

That question formed the basis of a prospective study published in Autism Research in 2025.

Researchers performed SI gene sequencing in 98 people on the spectrum who met the Rome IV criteria for IBS.

Seven percent were diagnosed with CSID.

The symptoms were exactly what you might expect: persistent diarrhoea, bloating and abdominal pain. Before receiving their diagnosis, many had already been treated for lactose intolerance, food allergies or IBS, often with little improvement.

The researchers also identified six different SI variants, including four that had never previously been described.

Taken together, these studies tell an important story.

CSID is unlikely to explain gastrointestinal symptoms in everyone with autism.

But among people on the spectrum living with persistent digestive symptoms — particularly diarrhoea, bloating and abdominal pain — it appears to be common enough that it deserves consideration rather than dismissal.

And perhaps most importantly, it is a diagnosis that can easily be overlooked if nobody thinks to look for it.

If the evidence is growing, why are so many people still being missed?

CSID rarely announces itself in an obvious way.

Not everyone develops severe symptoms in infancy, reacts dramatically after sugary foods, or can easily connect what they ate with how they feel afterwards. For people on the spectrum, recognising these patterns can be even more difficult, especially when pain, bloating or discomfort are hard to identify, describe or communicate.

Symptoms of sucrose or starch maldigestion may also appear hours after eating, unlike an immediate food allergy. By then, the meal responsible may be long forgotten.

Food preferences can cloud the picture further. Many people on the spectrum rely on familiar, predictable foods that feel safe, and those foods are often rich in starch, sugar or both. This means the foods contributing to symptoms may be eaten every day, making the relationship harder to see.

CSID itself also exists on a spectrum. Some people have severe symptoms from infancy, while others have milder or fluctuating symptoms that do not match the “classic” presentation many clinicians were taught. Even a single pathogenic SI variant may be enough to cause symptoms in some people, particularly if enzyme activity is reduced below what that person needs to comfortably digest their usual diet.

Because CSID does not always fit the classic textbook picture, the underlying digestive problem can be missed. A similar problem can arise when autism-related diets are chosen without first identifying what is actually driving the gut symptoms.

Gluten-free and casein-free diets are among the most commonly discussed dietary approaches in autism. Some people report meaningful improvement, while others see little change despite significant restriction. One possible reason is that not everyone is dealing with the same underlying biology.

If symptoms are driven by coeliac disease, food allergy or lactose intolerance, removing gluten, dairy or lactose may be appropriate. But if the real problem is sucrase-isomaltase deficiency, a person may cut out bread and milk while still eating gluten-free cereals, rice crackers, potatoes, fruit juice and sweet snacks — foods that can remain high in starch or sucrose.

The diet has changed dramatically, but the physiological problem has not.

Nutrition works best when the dietary strategy matches the biology. If the problem is carbohydrate maldigestion, the treatment needs to address carbohydrate digestion. Otherwise, people can spend years avoiding foods that were never responsible, while the true trigger stays hidden in plain sight.

CSID is genetic, but sucrase-isomaltase deficiency is not always congenital

Although this article has focused on congenital sucrase-isomaltase deficiency, not every case of reduced sucrase-isomaltase activity is inherited.

The sucrase-isomaltase enzyme sits on the brush border of the small intestine, a delicate surface that can be affected by inflammation, infection or other forms of intestinal injury.

When that happens, enzyme activity may fall even though the SI gene itself is completely normal. This is known as acquired sucrase-isomaltase deficiency, or ASID.

This distinction matters because inflammation of the small intestine can reduce brush border enzyme activity. Gastrointestinal inflammation has also been reported in some people on the spectrum with chronic digestive symptoms, although it is not present in everyone. In the Kushak study, only 6% of participants had duodenal inflammation, but those with inflammation often had marked reductions in digestive enzyme activity.

Whether the enzyme deficiency is congenital or acquired, the symptoms can look remarkably similar.

In some situations, genetic testing, disaccharidase enzyme analysis and the broader clinical picture are all needed to determine what is driving the symptoms.

Why this matters

Too often, people living with chronic digestive symptoms are told they have IBS, advised to try another elimination diet, or encouraged to simply manage their symptoms.

For many, that advice may be appropriate. But for others, it may mean years of treating the wrong problem — while CSID, a condition that can be identified and, in many cases, managed effectively, goes unrecognised.

People on the spectrum deserve the same careful clinical reasoning as anyone else.

In practice, that starts with asking the question: is this CSID? This means speaking with a GP, gastroenterologist, or dietitian/nutritionist familiar with the condition, rather than assuming persistent bloating, pain or diarrhoea is simply part of life with autism.

Disaccharidase activity can be measured directly via biopsy, and SI gene sequencing can identify relevant variants. For some people, a structured starch- and sucrose-reduced diet, guided by someone familiar with the condition, is enough to bring years of symptoms under control.

The goal should not be simply to manage symptoms. It should be to understand why they are happening in the first place.

Sometimes the answer really is IBS.

Sometimes it is not.

The challenge is knowing the difference.

References

Zubarioglu T, et al. Exploring congenital sucrase-isomaltase deficiency in autism spectrum disorder patients with irritable bowel syndrome symptoms: A prospective SI gene sequencing study. Autism Research. 2025;18(1):44–55.

Kushak RI, Lauwers GY, Winter HS, Buie TM. Intestinal disaccharidase activity in patients with autism: effect of age, gender, and intestinal inflammation. Autism. 2011;15(3):285–294.

McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014;133(5):872–883.