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 children 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 some 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.

For decades, CSID was considered a rare childhood disorder that became obvious as soon as sugary foods were introduced during infancy. Children would suffer 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.

Why researchers started looking at CSID in autism

The link does not come from the idea that CSID is “an autism condition.” It comes from a much simpler observation: 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 can all occur when sugars and starch-derived carbohydrates remain undigested in the gut. That 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 with autism 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?

One of the biggest challenges with CSID is that it rarely announces itself in an obvious way.

Not everyone develops severe symptoms in infancy. Not everyone reacts dramatically after eating sugary foods. And not everyone can easily connect what they eat with how they feel afterwards.

For people on the spectrum, recognising these patterns can be even more difficult.

Stomach pain may feel different. Bloating may be difficult to describe. Symptoms may simply register as feeling "off," without a clear connection to a particular meal.

Timing also makes things complicated.

Unlike an immediate food allergy, symptoms of sucrose or starch maldigestion may develop hours after eating. By then, the meal responsible has often been forgotten, making it incredibly difficult to identify patterns through observation alone.

Food preferences can further cloud the picture.

Many people on the spectrum rely on familiar, predictable foods that feel safe from both a sensory and emotional perspective. Those foods are often rich in starch, sugar, or both, meaning the foods driving symptoms may be eaten every single day.

When something has always been part of your diet, and you have always experienced digestive problems, it becomes remarkably difficult to recognise that the two might be connected.

Adding to the complexity, CSID itself exists on a spectrum.

Some people experience severe diarrhoea and obvious carbohydrate intolerance from infancy. Others have milder symptoms that fluctuate over time. Some have difficulty digesting both sucrose and starch-derived carbohydrates, while others appear to be primarily affected by sucrose.

Even carrying a single pathogenic SI variant may produce symptoms that do not resemble the “classic” descriptions many clinicians were taught.

It is little wonder that many people spend years living in diagnostic limbo: unwell enough to know something is not right, but never fitting neatly into the textbook picture.

Are we sometimes removing the wrong foods?

This is where the conversation becomes particularly interesting.

For decades, gluten-free and casein-free diets have been among the most commonly discussed dietary approaches for autism. Some people genuinely report meaningful improvements, while others notice little change despite making substantial dietary sacrifices.

One possible explanation is that not everyone is dealing with the same underlying biology.

If someone’s symptoms are being driven by coeliac disease, food allergy, immune mechanisms, lactose intolerance or another condition, then removing specific foods may be entirely appropriate.

But if the underlying problem is sucrase-isomaltase deficiency, the foods provoking symptoms may be completely different.

A person may diligently eliminate bread and milk while continuing to eat generous amounts of gluten-free cereals, rice crackers, potatoes, fruit juice, sweet snacks or processed gluten-free products that remain high in starch or sucrose.

In that situation, the diet has changed dramatically, but the physiological problem has not.

This highlights an important principle that extends well beyond CSID.

Nutrition works best when the dietary strategy matches the biology.

If the underlying problem is carbohydrate maldigestion, then the treatment needs to address carbohydrate digestion. Otherwise, people can spend years avoiding foods that were never responsible for their symptoms while the true trigger remains 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.

CSID is unlikely to explain every case of gastrointestinal symptoms in people on the spectrum. The evidence does not suggest that.

What it does suggest is that CSID appears common enough among people with persistent digestive symptoms — particularly diarrhoea, bloating and abdominal pain — that it deserves a place in the differential diagnosis. It is a condition that can be identified and, in many cases, managed effectively once recognised.

Perhaps the most important message is this: persistent digestive symptoms should never be dismissed simply because someone has autism.

People on the spectrum deserve the same careful clinical reasoning as anyone else. Sometimes the explanation is functional. Sometimes it is inflammatory. Sometimes it is lactose intolerance, coeliac disease, food allergy or reflux. And sometimes, it may be an overlooked enzyme deficiency such as CSID.

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.