GEMMA LogoA versatile team of doctors and scientists at the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital, MassGeneral Hospital for Children, and the Lurie Center for Autism, as well as at several international sites, have launched the GEMMA study to learn more about each of the many factors that contribute to the development of autism spectrum disorder (ASD). This long-term, multicenter study follows infants who are genetically at-risk of developing ASD for their first three years of life, with visits that can be completed at your local pediatrician’s office. Infants can even be enrolled before birth! Explore our website to learn more about how you can get involved!

Other participating organizations include: EBRIS; Nutricia Research; Medinok; Bio-Modeling Systems; Euformatics; Theoreo; National University of Ireland Galway; Azienda Sanitaria Locale Salerno; Harvard Medical School; Consiglio Nazionale delle Ricerche; INRA; INSERM; Utrecht University; University of Tampere; Imperial College London and John Hopkins University.

The GEMMA study is currently recruiting infants 0-6 months of age who have a full, biological sibling diagnosed with ASD.

About GEMMA

GEMMA stands for Genome, Environment, Microbiome and Metabolome in Autism. What does that mean? It is not well known exactly what factors contribute to the development of autism spectrum disorder (ASD). With the GEMMA study, we are taking as many of those factors into consideration as possible and studying how they each contribute to this complex neurodevelopmental disorder. As of today, there are no proven biomarkers of ASD and diagnosis relies entirely on behavioral evaluation. The biomarkers identified in this project will contribute to a better understanding of ASD development in at-risk children and lead to possible solutions for alleviating and/or preventing ASD symptoms and gastrointestinal comorbidities (conditions occurring at the same time) in future patients.

Genome

The word “genome” refers to the genetic information, or information from DNA, that everyone inherits from their parents. All living things are made of cells, and genes are the part of cells that contain the instructions that tell our bodies how to grow and function. Genes determine physical characteristics such as hair and eye color and are passed down through families. In the GEMMA study, we will be studying children who have a full, biological sibling with ASD, so that we can understand how their genes may contribute to the development of ASD. Today, scientists and doctors know that an individual’s risk of developing ASD is increased over 10-fold if a full sibling has the diagnosis. However, there are currently no preventative steps to reduce or potentially eliminate this risk. We hope that the GEMMA study will help us learn more about these genetic factors and to identify and validate genes to make it easier to predict who will develop ASD.

Environment

Without a doubt, our environment and surroundings influence our health. In the GEMMA study, we will consider many environmental factors including method of delivery (vaginal or cesarean section), antibiotic use, breast or formula feeding and time of introduction to certain foods. We will also consider other aspects of your baby’s medical history including illnesses, infections, and growth over time. We hope to understand whether any of these factors, alone or in combination, contribute to the development of ASD. If we find that a particular factor, or combination of factors, increases the risk of developing ASD, we will be able to apply this information and help prevent and/or detect ASD onset in high-risk children in the future.

Microbiome

The human gut, comprised of the small and large intestines, is home to many types of bacteria. These bacteria help to break down and digest food, provide our bodies with energy, and make vitamins that the body needs to thrive. This diverse community of bacteria is called the gut microbiome. One of the most important roles of gut bacteria is aiding in the development of the immune system. It is believed that the gut microbiome plays a role in the development of ASD. In the GEMMA study, we hope to learn more about this relationship by studying the members of the gut microbiome before and after ASD development in the subset of enrolled infants who will develop this condition. By doing this, we will uncover patterns in the gut microbiome that may help us predict who will develop ASD before it happens.

Metabolome

The processes that occur in our gut, such as the digestion of foods and production of vitamins, create products that are called metabolites. The specific metabolites that we produce differ from person to person and depend on many factors, including our genes, members of the gut microbiome and food choices. The collection of metabolites produced by a sample is called the metabolome. We will study the metabolomes of different infants while noting any changes to their environment and monitoring them for ASD. Studying the metabolites in this way is called metabolomics. In doing this, we hope to find patterns, or specific metabolomic profiles, that might predict when someone may develop ASD before it happens.

How Gemma Is Making History

GEMMA Study: GEMM Babies are Leading the Future of Diagnosis and Treatment of Autism Spectrum Disorder

Soon the “autism community” as we know it will experience a historic and transformative shift in the landmark of how we identify, predict and prevent autism spectrum disorder (ASD). Excitingly, this landmark will stem from evidence collected from our youngest researchers – infants – and will come in the form of our GEMMA babies.

Now we’re uncovering hidden GEMMs to help us...

Our gut microbiome ­– the trillions of microbes that naturally reside in our intestines – has recently emerged as an important agent of maintaining the balance between health and disease. These intestinal microbes help us to break down or digest foods and even create important vitamins that our bodies need. Recent scientific evidence also suggests that these gut microbes and our immune system develop simultaneously, reciprocally influencing one another. Much of the development of our microbiome takes place during the early stages of life. When a person reaches three years of age, the microbial communities within the gut stabilize and reflect what researchers now recognize as an “adult-like” pattern. Despite this stabilization, food and medications can cause subtle alterations to our microbiome at any age, including which bacteria are present and in what quantity.

A doctor smiles at a onesie-clad baby who's sitting up on an examination table.
Alessio Fasano, MD, with a patient

We are hopeful that the secret to understanding why certain individuals develop ASD will stem from an in-depth look at the microbial communities and patterns present in the gut. A major aim of the GEMMA study is to validate the early microbial signature of ASD. Once achieved, the future standard of care for ASD will involve screening for the “pre-ASD” microbial signatures and administering treatments to help children achieve a healthier distribution of microbes. The newly introduced microbes would alter the host intestines, re-colonizing the gut in a fashion that is incompatible with the development of ASD. Through use of biospecimen samples (i.e. stool, urine, saliva and blood) collected from GEMMA participants, our research team aims to apply these principles to the identification and ultimate prevention of ASD, paving the way for the future of personalized treatment and prevention of this neurodevelopmental disorder.

About Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by challenges in social communication and interaction, as well as restrictive, repetitive patterns of behavior and interests. Although ASD can be diagnosed at any age, it is said to be a “developmental disorder” because symptoms generally appear in the first three years of life. ASD is a “spectrum” because the presentation and severity of symptoms widely vary among affected individuals. In addition to behavioral and neurological symptoms, individuals diagnosed with ASD tend to have more medical issues than those without an ASD diagnosis. These can include gastrointestinal symptoms such as chronic constipation, diarrhea, abdominal pain, bloating, nausea, reflux and vomiting. As documented by the Centers for Disease Control and Prevention (CDC), ASD is present across all races, ethnicities, and socioeconomic groups. It affects 1 in 59 children worldwide with 4 males to every female diagnosed. This rising prevalence represents a 40-fold increase since 1960. While the factors contributing to increases in reported rates of ASD, and to ASD pathogenesis in general, are not fully understood, research suggests an explanation might be found in the interplay between various environmental and genetic risk factors.

Want to learn more about ASD? We suggest visiting these websites:

Frequently Asked Questions

I’m pregnant. Can I start the enrollment process now?

Yes! We encourage parents to consider enrollment as early as during pregnancy. Though sample collection for the study won’t start until your child’s time of birth, enrolling during pregnancy provides a unique opportunity to follow your child’s gut microbiome (see “About GEMMA” for more information about the gut microbiome) from the earliest stages.

I’m not planning on introducing solid foods until my child is six months old. Why should I enroll before then?

In order to understand how early environmental factors may contribute to the development of autism spectrum disorder (ASD), it is best if we begin collecting samples and data from birth. We know that the first year of life is an incredibly important period in a child’s development, particularly for the immune system and the gut microbiome. Obtaining early biospecimen samples and clinical information will allow us to best determine how early environmental factors affect the development of ASD in children. This will provide a more complete picture of microbial changes or environmental triggers that may contribute to ASD onset.

What if my husband/wife/child with ASD do not want to donate samples? Is this required?

At enrollment, the baby’s sibling who has been diagnosed with ASD and at least one, but preferably both, parent(s) will provide one-time blood, stool, urine and saliva samples. These samples are crucial to our study analysis in order to distinguish between inherited and de novo (newly arising) properties, and to better detect the variants related to ASD. Therefore, obtaining consent to collect one-time samples from the baby’s sibling with ASD and at least one of their parents is an inclusion criterion for the study.

I’m interested in having my child participate in GEMMA. How do I get started?

Email us at MGHGEMMA@mgh.harvard.edu to get the enrollment process started. We will answer any questions you may have and discuss the study in a bit more detail, including going over the study consent form. We can also direct you to a local site, if there is one near you, or help you speak with your child’s pediatrician about participating in the study (see below).

What do I do if I want my infant to participate in the study, but I can’t find a center near me?

Study visits can be completed “remotely.” Stool, urine and saliva samples can be collected at home, and blood draws can be completed at your child’s pediatrician or at a walk-in medical facility. Your participating site will mail all sample collection materials and instructions to you when your child reaches a collection milestone. At time points that involve a diagnostic evaluation for ASD, you will be referred to a study-affiliated developmental evaluation center near you. At this center, your child will complete study assessments with a certified psychologist. Contact the participating site closest to you to learn more about the study timeline and what each time point entails.

My child has a stool/urine/saliva sample coming up, but I can’t remember how to collect it.

No problem! See below.

How to Get Involved

Join us! Come participate in the Genome Environment Microbiome and Metabolome in Autism (GEMMA) study.

Who Can Participate?

Infants must have a sibling who is diagnosed with autism spectrum disorder (ASD) to be eligible to participate. Infants must also have not yet been introduced to solid foods. If you are currently pregnant, and your infant-to-be will fulfill these criteria, you can get the enrollment process started – even before birth!

What Is Involved?

Your child will complete a study visit every six months until they reach three years of age. Not all visits will involve all of the following procedures; we will inform you when it is time for a visit and what is required at that visit.

Screening and Enrollment

Once your baby is enrolled, we will first ask you to fill out a questionnaire addressing the medical and dietary history of the participating family members [sibling(s) with ASD and parent(s)]. Pregnancy and birth data for mom and baby will also be recorded. This information is important so that we can fully understand all your baby’s GEMM details. At enrollment, the baby’s sibling diagnosed with ASD and mom and/or dad will be asked to provide one-time blood, stool, urine and saliva samples. Depending on the baby’s age at enrollment, he or she will also provide these samples.

Sample Collections

The study will involve periodic collection of blood, stool, urine and saliva from your baby during his or her first three years of life. Sample collection materials can be delivered right to your home. All samples are collected every six months until age three. Stool, urine and saliva are to be collected from the baby at home, and we can help arrange for blood samples to be collected at your pediatrician’s office or another local lab of your choosing. Return shipping materials are provided in each sample kit for you to return samples to the study site overnight after collection.

Collection of Clinical Data

Your baby’s clinical and dietary information will be collected during his or her first three years of life. Any study forms will come to your email automatically at the required time points. These quick forms are completed monthly in order to obtain the most accurate history of illnesses, antibiotic use, introduction of foods, and general dietary history. The answers to these questions will help us understand your child’s environment so that we can study how it relates to their blood, stool, urine and saliva samples.

Early Autism Diagnosis

Your child’s development will be monitored throughout the study, and assessments will be administered every six months starting at one year of age. This way, if your child develops ASD while enrolled in the study, you will have a confirmed diagnosis as soon as signs emerge and can begin an intervention plan as early as possible with a well-qualified staff member on our team. In addition, your child would qualify to participate in a subsequent interventional arm of the GEMMA study, which will use the identified biomarkers to implement personalized prevention and treatment of ASD and ASD-related symptoms. If your child does not develop ASD, you will also have access to that information as early as possible.

Participating Centers

United States

Principal Investigator: Sarah Kadzielski, MD
Investigator: Alessio Fasano, MD
Investigator: W. Allan Walker, MD
Mucosal Immunology and Biology Research Center
MassGeneral Hospital for Children
Boston, MA
Contact: MGHGEMMA@mgh.harvard.edu or (617) 643-6918
Currently Recruiting

International

Principal Investigator: Geraldine Leader
National University of Ireland Galway
Irish Centre for Autism & Neurodevelopmental Research
Galway, Ireland
Contact: geraldine.leader@nuigalway.ie or visit www.icanautism.ie
Currently Recruiting

Principal Investigator: Giulio Corrivetti
The Azienda Sanitaria Locale Salerno
Salerno Autism Network
Salerno, Italy
Contact: g.corrivetti@aslsalerno.it
Currently Recruiting

Meet the Team