A team of researchers and clinicians in Spain has studied if differences in the microorganisms that live in the digestive tract, known as the gut microbiome, can help to understand gastrointestinal (GI) symptoms in Sanfilippo.
GI disturbances are common in people with Sanfilippo, who can experience chronic or recurrent non-infectious diarrhoea and/or constipation. As noted in the Global Consensus Clinical Care Guidelines for Sanfilippo, GI symptoms are among the early signs of the disease and may also worsen behavioural symptoms, sleep disturbance, pain and distress. All of these symptoms affect quality of life for the affected individual and their family.
There are some known drivers of GI disturbances, including diet, infection or antibiotic treatment; but these alone cannot explain the GI symptoms and the variation seen between patients. A deeper understanding of why these symptoms develop, including the role of the gut microbiome, is needed.
In this study, the team explored why two 12- and 13-year-old siblings with Sanfilippo type A have different GI symptoms, with one experiencing recurrent diarrhoea. This is despite the siblings sharing the same Sanfilippo genetic variant and the same diet. Each sibling’s gut microbiome was compared, along with the gut microbiomes of four age-matched healthy volunteers on a restriction-free diet.
The children with Sanfilippo had higher fecal heparan sulfate (HS) levels than the healthy volunteers. HS is the complex sugar that builds up in the disease, so this result is expected. However, fecal HS levels differed between the siblings: the child with the worse GI symptoms had nearly double the concentration of HS in their stool.
By analysing the bacteria in the fecal matter, the researchers found a lower microbiome diversity in the siblings with Sanfilippo. There were also differences in the abundance of bacterial families between the siblings. The clearest difference was in one group of bacteria known as Bacteroides.
Interestingly, some Bacteroides bacteria can use HS as an energy source. The researchers found the sibling with worse GI symptoms had lower levels of Bacteroides bacteria and the bacterial genes required to break down HS.
The team reviewed the siblings’ current treatment regimes and found only the sibling with worse GI symptoms was prescribed an antipsychotic drug called levomepromazine. They exposed a type of Bacteroides bacteria to this drug and found bacterial growth was inhibited. They suggest the drug may contribute to the lowered Bacteroides levels, leading to more HS in the gut and worse GI symptoms in the sibling.
While this study only references the findings in one set of siblings and cannot be generalised to all people with Sanfilippo, it does highlight the need for further investigation into the microbiome and potential drug side effects in Sanfilippo syndrome. Prescriptions and their side effects should always be discussed with the child’s clinical team, with treatments modified only under medical supervision.
Funding for the study included grants from Fundación Mutua Madrileña, Instituto de Salud Carlos III and the European Union.
