Tell us about yourself. How has your academic life been?
I am Dr Chandrashekhar Thodupunuri. I did my MBBS at Prathima Institute of Medical Sciences, and I pursued my postgraduate diploma in clinical cardiology from Apollo Hospital, Hyderabad. I worked at Apollo Hospital, Global Hospital and Archana Hospital as a cardiologist.
Research based healthcare startup to find solution for a healthy upcoming generation
My career took a significant turn when my child got diagnosed with autism. In pursuit of a solution for her condition, I did a fellowship program at the Medical Academy of Pediatrics, Special Needs in the USA. My research about autism taught me that it is preventable. This possibility made me leave my cardiology career and pushed me into autism research.
The health care & Life science sector is going through a rapid shift. How does it encourage you to establish Providence Microbiome Research Center?
During my journey of autism research, I happened to meet some extraordinary researchers and amazing parents who recovered their children with autism. I understood a concept called the “hologenome theory of evolution” from recovery stories, which is most relevant for autism and many other illnesses.
According to our research, the human body and a few species of microbes living in the human gut work together as a single unit at the genome level, i.e., the human genome and these microbial genomes work in tandem as a shared gene pool. These shared gene pools, which were developed during evolution, form an epigenetic medium necessary for human development and the typical day-to-day functioning of the human body. These microbes undergo vertical transfer from the mother’s uterus to the child during pregnancy.
Any disruption in this shared gene pool will result in epigenetic errors and lead to diseases like diabetes, obesity, cancer, neurodegenerative disorders, psychiatric illnesses, etc. If this gene pool is affected in foetuses during pregnancy, it leads to adverse outcomes like autism and global developmental delay.
Gross epigenetic errors in postmortem brain tissues of autistic individuals and phylogenetically different ecosystems in gut microbial studies in autism made me think in the direction of microbiome research. Although “faecal microbiota transfer therapy” is an option to transform these gene pools to correct the epigenetic errors in autism, research related to the gut microbiome, human epigenetics and its relevance to autism is minimal and sparse.
Around 421 clinical trials regarding faecal microbiota transfer therapy were registered across the globe for various diseases, of which seven were registered for autism. Most of these clinical trials are done by academicians. Though these concepts are helpful for human health, they do not get enough opportunity to complete the drug research process due to the high costs involved. Also, as there is no drug to sell in FMT research, investors do not show much interest in investing in microbiome research.
We at Providence Microbiome believe in the adage that prevention is better than cure. If we can protect human embryos from alterations in a shared gene pool, children might escape from Autism Spectrum Disorder (ASD). This possibility made me establish a research startup to conduct a series of academic clinical trials to propose antenatal programs to prevent ASD.
What are your objectives and motto?
Our objective is to test faecal microbiota transfer therapy (FMT) 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. Furthermore, if the concept is proven, we will establish the aetiology and pathophysiology of autism and propose an antenatal program for autism prevention.
Tell us something about your research facility?
Providence Microbiome Research Center Pvt Ltd. has collaborated with the Center for DNA Fingerprinting and Diagnostics – National Genomics Core (CDFD-NGC), a DBT institute for genetic and epigenetic testing Microbiome Research Pvt Ltd, miBIOME therapeutics Pvt Ltd and Agenes Info Omics Pvt Ltd for microbiome testing. We partnered with KSbioclinserve, Inductive Quotient Analytics, and St Theresa’s Hospital for clinical trials. We are working exclusively on autism, and our research mainly focuses on genetics, epigenetics, and the role of the gut microbiome.
Tell us about your research topics. Also, can you share the results with us?
We are conducting a series of clinical trials. The first of the five planned studies is “faecal microbiota transfer therapy for autism” or “gut symbiont restoration therapy,” registered with ICMR, and we are currently recruiting patients. In another human trial, we will study the umbilical cord blood toxins and meconium microbial composition and developmental outcomes to establish the aetiology and pathogenesis of autism. Of the three planned animal studies, two are to test the hypothesis; one animal study is intended to test the safety and efficacy of the antenatal program. At the end of all these five studies, human trials will be done to test the safety and effectiveness of antenatal programs to prevent autism.
We recruited a few children with autism for our trial; the preliminary results are satisfactory and promising. In addition, we have observed that supernatant fluid obtained from screened donor stool gives better and faster results than regular faecal microbiota transfer therapy. If the results are consistent, FMT has the potential to become the treatment of choice for autism.
How are you managing funds to run your research?
Currently, we are conducting research with self-generated funds. We plan to get some funds from the Startup India seed fund scheme. We will seek Government and some other private grants after satisfactory preliminary results.
Which factors are majorly contributing to destabilising brain tissue in infants?
When we look at the history of autism, it has been rising in the last 40 years. The incidence of autism in 1980 was 1 in 10,000, which increased to 1 in 54 by 2020. Human beings evolved 2 million years ago, but this situation never existed earlier. Furthermore, the incidence of autism is higher in most developed countries. It indicates that society has been doing something wrong for the past 40 years.
Around 80,000 chemicals are registered with the Environmental Protection Agency, USA. 2500 new chemicals are being introduced every year, of which only 5% of the chemicals are officially declared as toxic to human beings. We are using these chemicals in 4 lakh products. Most of them resist human metabolism and accumulate in the human body.
Biological processes in any living organism develop over generations upon constant exposure to environmental challenges. However, human beings do not possess mechanisms to excrete many toxins like microplastics (detected in human blood recently). These toxins will be the biggest threat to humanity and even lead to human extinction.
In a cord blood study between 2007 and 2009, Rachel Network and the Environmental Working Group found 232 toxins in umbilical cord blood. Bisphenol A, pesticides, preservatives, and industrial toxins are significant cord blood components, which means human embryos are developing in a toxic medium.
We hypothesise that these toxins are the major factors that prevent the transfer of evolutionarily related microbes into foetal intestines leading to significant alterations in foetal and microbial shared gene pools, thereby leading to epigenetic errors, autism and global developmental delay.
Sometimes the children acquire a phylogenetically different ecosystem and develop severe autism from birth. In some cases, the children inherit evolutionarily related microbes and a phylogenetically different ecosystem, considered a susceptible microbiome. Triggers like antibiotics depopulate these evolutionarily related microbes, and children develop sudden onset of epigenetic errors and land up in regressive autism.
Can you simplify autism for the common public?
An understanding of the nervous system is essential to know about autism. The nervous system is the most sophisticated organ in the animal kingdom. It is a command centre for any animal, which will collect information from its surroundings, processes the information, and gives commands to the body to enact according to external stimulus. The capabilities of nervous systems among animals are widely variable, with varying sets of skills and increasing complexity.
Humans are at the pinnacle of evolution in the nervous system, which has a very complex structure and microarchitecture with very specialised brain cells containing many brain proteins. The human brain collects information from surroundings with sensory organs like skin, ears, eyes, tongue, and nose, which collect information and convert it into the chemical message in the form of neurotransmitters and convey the message to the central nervous system through sensory neurons. The central nervous system processes the information, plans a motor activity, and commands the body to act accordingly. Apart from this primitive skill, the human brain can think and reason, develop memory, intellect, emotions, social skills, insight, speech, language, etc.
The brain tissue with the highest capabilities has a complex structure with specialised cells. Brain development during the foetal stage consists of a complex orchestra of events that require a wide range of structural and functional components. Structural proteins and functional proteins like neurotransmitters are synthesised from their respective genes. The epigenetic medium is crucial in running this complex orchestra of events during brain development and its function. As the epigenetic medium is affected due to alteration in shared gene pools in autism, multiple proteins are produced in unusual quantities (around 584 proteins are produced in excess, 558 proteins produced in minor amounts, and around 833 structurally abnormal proteins). This kind of abnormal protein formation affects brain development.
Processes like neurogenesis, neuronal migration, neuronal differentiation and microglial activation are affected, leading to brain microarchitecture abnormalities with an excess number of neurons (brain cells), an extra number of synapses (connections between brain cells), neuronal immaturity leading to dysfunctional brain circuitry and underdeveloped brain areas.
This underdevelopment can be widely variable among affected individuals with a broad spectrum of impaired brain functions. As this underdeveloped brain cannot take proper sensory inputs from sensory organs, they face difficulty with external noises, lights, smells, textures, etc. These are referred to as sensory issues. Along with sensory input deficits, information processing and motor planning are also affected, so planned motor activities and fine motor skills are underdeveloped. Hence, they face problems using their fingers to do fine motor activities. Thought, memory, intellect, language, speech and many other functions are affected, so they cannot process the social signals and have poor socialisation and communication. Because of underdeveloped brain tissues and dysfunctional circuitry, their brain has the tendency to stimulate, which causes constant stimming and repetitive behaviours. Symptoms are variable according to the extent of underdevelopment of brain tissues.
Currently, there is no established cause and no proven treatment for autism. ABA, speech therapy and occupational therapies are considered alternative options to train the kids for daily life activities.
How is autism affecting the current and upcoming generations?
- Children with autism have many co-morbid medical conditions apart from autism symptoms, which puts them in constant suffering. Medical professionals are unaware of their medical conditions, and children cannot communicate effectively. Most of the time, they are undertreated.
- The availability of therapists or professionals supporting autistic children is significantly less.
- Social stigma for families and enormous suffering for parents, and lack of awareness about the condition are the other significant problems with autism.
- With the growing number of autism incidence, future predictions look fearsome and diabolical. For example, some projections say that there will be an incidence of 1 in 10 by 2050, which means every pregnancy will be a nightmare.
What are the possibilities to reduce autism incidence?
Autism research is a global responsibility today. Governments and policymakers must focus on preventing autism rather than research related to managing autistic kids with therapies. Exclusive research centres should be established. Plastic use, pesticide use, and industrial toxin exposure should be minimised. Strategies are to be made to identify pregnant women with high toxin loads and apply detox protocols to prevent autism. N-acetylcysteine (NAC), used for high-risk pregnancies, can be considered an option to detox pregnant women with a high toxin load.
What are the issues correlated with autism that should be scrutinised to eliminate further mishappenings?
According to our research, autism can be due to genetic and non-genetic causes. Simmons Foundation’s Autism Research Initiative and Simons Powering Autism Research are two evolving datasets that identified around 1200 genes responsible for autism. Autistic children and parents must be screened for genetic abnormalities. In case of genetic reasons, parents should be counselled accordingly.
What are your views on combining current modern pharma technology and Ayurveda to eliminate medical issues?
Nature has gifted us with plenty of medicinal plants, which are not being used in modern medicine. The Pharma industry should extract active ingredients in medicinal plants described in ancient ayurvedic texts and use them in modern medicine with systematic research to benefit humankind.
Year of founding
Dr Chandrashekhar Thodupunuri & Dr Keerthi Sarabu
Eight medical doctors, four scientists, eight supporting staff