P2275 - Antibiotics Followed by an Ultra Filtrate Fecal Microbiota Transplantation Improves Symptoms of Autism in an Adult Male

Annabel K. Clancy, PhD, Anoja W. Gunaratne, PhD, MSc, Sibasish Dolai, PhD, Thomas J. Borody, MD, PhD, DSc, FRACP, FACG
Centre for Digestive Diseases, Five Dock, New South Wales, Australia

Introduction: Autism spectrum disorder (ASD) describes a group of disorders characterised by deficits in communication and social interactions. Gastrointestinal (GI) symptoms including abdominal pain and constipation frequently occur with ASD. Treatments that modulate the gut microbiota including antibiotics and fecal microbiota transplantation (FMT) have shown promise in the treatment of children with ASD and GI symptoms. However, these findings have not yet been reported in adults.

Case Description/Methods: The male patient (16yrs) was referred for assessment of severe, supra umbilical abdominal pain, slow bowel function and straining on defecation. The patient had been diagnosed with ASD at age 4. The patient was prescribed off label Vancomycin and Rifaximin (Table 1). Review at one month indicated improvements in bowel frequency and consistency, although abdominal pain persisted. Improvements in mental state were also reported including increased engagement in family activities and being calmer in nature. Addition of Tinidazole reduced abdominal pain and further improved organisational skills and collaborative work at school. The patient was referred for trial of Ultra-Filtrate (UF) FMT at aged 21yrs. UF FMT was produced using screened donor stool, which was homogenised with saline, passed through multiple sieves of decreasing size and centrifuged. Antibiotics were ceased and the UF was taken orally in home-made ice-cream. The patient completed a quality assessment form including taste and smell for the UF, an abdominal symptom questionnaire, Autism Spectrum Quotient (ASQ) questionnaire and Cambridge Behaviour Scale (empathy quotient) scores (CBS) at pre-FMT and week 14. The patient reported a very mild taste from the UF but that it was easy to take with an increase in flatulence in the first two weeks of treatment. No other adverse side effects were reported. At week 14 the patient reported bowel motions 1-2 times daily and no abdominal pain. A 4-point reduction in ASQ score and a 7-point increase in CBS was observed (Figure 1).

Discussion: To our knowledge, this is the first report of the use of antibiotics followed by UF FMT to treat GI symptoms and ASD in an adult patient. Combination antibiotics was effective in reducing abdominal pain and resolving constipation. Improvements in autistic traits were seen with antibiotic treatment. Follow on treatment with UF FMT further resolved abdominal pain and continued improvement in autistic traits were observed.


Figure: Figure 1: Change in ASD scores before and after treatment with Ultra-Filtered FMT
(a) Change in Autism Spectrum Quotient (ASQ) score before and after treatment with ultra filtered FMT. A score of ≥32 is considered to indicate clinically significant ASD traits
(b) Change in Cambridge Behaviour Score (CBS) before and after treatment with ultrafiltered FMT. A score of ≤20 indicates a lower than average ability for understanding how other people feel and responding appropriately and is associated with ASD.

	Baseline	Antibiotics Tx. 1	Antibiotics Tx. 2	Post FMT
Treatment	Nil	Vancomycin 250mg mane, 500mg nocte Rifaximin 500mg BD	Vancomycin 250mg mane, 500mg nocte Rifaximin 500mg BD Tinidazole 500mg BD	Day 1 and 2: Initial loading dose of 50ml TID Day 3-70: maintenance dose of 1.5ml daily
Duration of treatment (months)	N/A	4	48	2.5
Gastrointestinal symptoms	Severe, supra umbilical abdominal pain, slow bowel function and straining on defecation	Ongoing abdominal pain Improved bowel frequency and consistency	Reduced abdominal pain Improved bowel frequency (BO 2/day) and consistency	No abdominal pain BO 1-2/day
ASD symptoms	Difficulty concentrating/poor attention Anxiety/irritability Difficulty following basic instructions Difficulty with fine motor skills Difficulty with social situations	Increased engagement in family activities and generally calmer nature	Improvements in organisational skills and collaborative work at school	Improvements in concentration/brain fog

Table: Table 1: Summary of treatment regimen for adult male patient with GI symptoms and ASD

BD: twice a day, TID: three times a day, mane: morning, nocte: evening, BO: bowels open, mg: milligram, Tx: Treatment regimen


Disclosures:
Annabel Clancy: Centre for Digestive Diseases – Employee.
Anoja Gunaratne: Centre for Digestive Diseases – Employee.
Sibasish Dolai: Centre for Digestive Diseases – Employee.
Thomas Borody: Centre for Digestive Diseases – Advisory Committee/Board Member, Consultant, Employee, Grant/Research Support, Patent Holder, Stockholder/Ownership Interest (excluding diversified mutual funds).


Annabel K. Clancy, PhD, Anoja W. Gunaratne, PhD, MSc, Sibasish Dolai, PhD, Thomas J. Borody, MD, PhD, DSc, FRACP, FACG. P2275 - Antibiotics Followed by an Ultra Filtrate Fecal Microbiota Transplantation Improves Symptoms of Autism in an Adult Male, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.