There’s no love like the love of a parent. As a parent myself, I know that I would do anything for my children.
For Dr Chandrashekhar Thodupunuri, his daughter’s autism spectrum disorder (ASD) diagnosis set him on a groundbreaking journey from the world of cardiology to the forefront of autism research.
Driven by a deeply personal experience, his current mission has been to transform the landscape of autism care. He is now in the middle of ICMR-approved research projects — one on prevention of autism by treating it at the foetal stage and another on faecal microbiota transplantation to manage autism.
“I am a cardiologist by profession,” he begins, “My daughter was born in 2015 and a year later, she was diagnosed with autism. In the meantime, we saw that she had severe gut health issues. This journey towards finding a solution for her gut problems led me down the research route to understand the role of the gut microbiome in children with autism spectrum disorder and whether treating that will improve the behavioural symptoms and overall quality of life of autistic children.”
What is to be autistic?
According to doctors, in individuals with ASD, their brains function and interpret information in a way that can result in challenges in social interactions, understanding social cues, emotional regulation, communication issues like difficulty in conversing, paying attention, learning and processing information.
The signs typically begin in early childhood and stays throughout the individual’s life.
Though this has been a topic of research and debate, there are only speculations regarding the possible causes of autism. However, a number of risk factors for autism have been listed by researchers. This includes mutations in one or more genes, exposure to environmental toxins, dysregulation of the immune system, and complications during pregnancy and birth.
However, Dr Chandrashekhar’s research is trying to identify the role of the gut microbiome in the development of autism spectrum disorders.
A personal turning point
After his MBBS, Dr Chandrashekhar pursued his postgraduate diploma in Clinical Cardiology from Apollo Hospitals and began his practice in cardiology.
But in 2016, after his daughter’s ASD diagnosis, Dr Chandrashekhar decided to pivot and take up the Medical Academy of Pediatrics, Special Needs Fellowship in the USA, the only comprehensive programme for treating medical issues associated with special needs, autism spectrum, and neurodevelopmental disorders.
During this fellowship, after scores of interaction with several doctors and researchers, Dr Chandrashekhar came to one profound conclusion — autism is preventable.
“With knowledge about drug research, clinical trials, and regulatory systems, I decided to conduct systematic research into autism to help my daughter’s condition,” explains Dr Chandrashekhar.
Interestingly, the doctor was also trying to improve his daughter’s gut health, which was causing her a lot of trouble. During his interaction with researchers and parents who were working towards autism recovery, Dr Chandrashekhar chanced upon the concept of “hologenome theory of evolution”, which is relevant not only to autism but also to many other illnesses.
During his research, he realised that there is a connection between the gut and the brain. Sometimes, changes in the genes can also lead to problems in the gut and throw off the balance of the gut ecosystem. In children with autism, they often have a specific change in the types of organisms living in their gut.
Explaining further, Dr Chandrashekhar says, “Children with ASD have fewer good bacteria that help in controlling inflammation and more of the bad ones. These bad bacteria can produce substances that can make autism symptoms worse.”
Faecal microbiota transplantation
That is when he attempted faecal microbiota transplantation (FMT), which is typically used to treat recurrent C difficile colitis, a condition that can cause serious digestive problems.
Surprisingly, not only did her gut health improve with this treatment, she even began to show some neurological developments in her brain. Her behaviour started to improve too, strongly indicating a gut-brain connection in children with autism.
“This discovery prompted me to think about finding out if there is a tie between ASD and gut microbes. I decided to shift my focus from cardiology and start a centre to research this treatment in about 100 children, aged between 3 and 17 years, all from Hyderabad. This is an ICMR-registered study and we started doing this in February 2022. It will be completed in another three years’ time,” he says.
The study aims to test faecal microbiota transplantation as an appropriate treatment modality for autism.
“If FMT is proven successful, we would like to develop a serum marker for autism by conducting a large-scale epigenetic study comparing normal and autistic children. Further more, we will establish the etiology and pathophysiology of autism and propose an antenatal programme for autism prevention,” he explains.
Discovering the gut-brain connection
Dr Chandrashekhar’s extensive research unveiled evidence suggesting that the human microbiome, specifically certain microbes passed from mother to child, play a vital role in human development.
Explaining further, Dr Chandrashekhar says, “Our gut has a community of tiny organisms that live inside it, known as gut microbiome. It’s like a mini ecosystem in our digestive system. These organisms have a big influence on everything in our body, research is showing links to various disease, even in our brains.”
After conducting genetic tests on himself, his wife, and his daughter, Dr Chandrashekhar realised that his daughter’s autism was not due to genetic factors. During his research on recovery from autism, he found that the human body and a few species of microbes living in the human gut work together as a single unit at the genome level.
The human genome and these microbial genome work in tandem as a shared gene pool. This gene pool was developed during evolution and form an epigenetic medium necessary for human development and the typical day-to-day functions of the human body. These microbes undergo vertical transfer from the mother’s uterus to the child during pregnancy.
With this finding, the doctor has now embarked upon a new large-sample study through which he is attempting to prevent birth of autistic children by treating pregnant mothers at the antenatal stage.
How a mom’s gut bacteria can affect autism
To research and treat pregnant women, Dr Chandrashekhar set up Providence Microbiome Research Center Private Limited, a centre that enables a toxin-free pregnancy for an “autism-free generation”.
He explains, “The uterus is not sterile. Developing foetuses have micro friends helping in gene expressions during development. Toxins entering the foetus cross the placental barrier and toxins, which enter the foetus, kills the friendly microbes, resulting in epigenetic errors. Epigenetic errors affect neuronal migration, neuronal differentiation, and functional circuitry formation, leading to autism. Hence, toxins must be avoided in pregnancy.”
He adds that gross epigenetic errors in postmortem brain tissue of autistic individuals and phylogenetically different ecosystems in gut microbial studies in autism made him think in the direction of microbiome research.
At the centre, pregnant women are given a detox treatment and are also treated with a prevention model. Pregnant women are given N-acetyl cysteine in antenatal programme, along with folic acid and other vitamins.
Also, plastics, pesticides, cosmetics, etc, are avoided during the pregnancy and they are encouraged to eat only organic food to help prevent toxins from entering the body. “Providing a toxin-free environment to a developing foetus can lead to a healthy baby without autism,” explains Dr Chandrashekhar.
While faecal microbiota transplantation is an option to transform these gene pool to correct the epigenetic errors in autism, research related to the gut microbiome, human epigenetics, and its relevance to autism is minimal and sparse. So, at Dr Chandrashekhar’s Providence Microbiome Research Center, it is believed that prevention is better than cure.
Keeping this in mind, the doctor at the research centre aims to conduct a series of academic clinical trials to propose antenatal programmes to prevent ASD.
What happens at the research facility?
The Providence Microbiome Research Center has collaborated with the Department of Biotechnology-funded Center for DNA Fingerprinting and Diagnostics — National Genomics Core (CDFD-NGC), Microbiome Research Private Limited, miBiome Therapeutics Private Limited, and Agnes Info Omics Private Limited for microbiome testing.
The centre has also partnered with KS Bio Clinserve, Inductive Quotient Analytics, and St Theresa’s Hospital for clinical trials. The centre is exclusively working on autism and the research mainly focuses on genetics, epigenetics, and the role of gut microbiome.
Dr Chandrashekhar adds that the first of the five studies that have been planned is faecal microbiota transplantation for autism, which is registered with ICMR, and 100 samples are being studied for this.
Meanwhile, in another human trial, the researchers intend to study the umbilical cord blood toxins and meconium microbial composition and development outcomes to establish the etiology and pathogenesis of autism.
Of the three animal studies planned, two are to test the hypothesis: one animal study is intended to test the safety and efficacy of the antenatal programme. At the end of all these five studies, human trials will be done to test the safety and effectiveness of antenatal programmes to prevent autism in humans.
The centre, which is currently managing research using self-generated funds, plans to seek grants and funding from the government and private sources, once there is satisfactory preliminary results.