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Gut-Brain Connection in Autism Spectrum Disorder

Although there is no direct evidence that gastrointestinal (GI) symptoms and Autism Spectrum Disorder (ASD) have a cause-effect relationship, studies have suggested that the gut has an important role in the aetiology of ASD.1


Initial Consult


When we first met, this 2.5 year old patient weighed 15.6kg and had two large spots of hair loss. Although he was undergoing behavioural assessments at the time, his parents brought him to clinic to seek treatment for the hair loss. He was a fussy eater and it had been particularly difficult to get him to eat dinner for more than a year. He had ‘quite offensive stools’, which ‘smelt like LPG gas, with even the smallest amount smelling strongly’. Occasionally there would also be mucus present with undigested food and a pale colour. The patient suffered recurrent illnesses from childcare including upper respiratory tract infections (URTI), ear infections, as well as hand, foot and mouth disease.

His dermatologist diagnosed him with alopecia and he was diagnosed as ASD level 3 by his paediatrician. His sensory issues were first noticed at age 2 and involved covering his ears, increased sensitivity to loud noises as well as being behind in his speech while his play often seemed to be a source of distress and was non-imaginative. He regularly experienced ‘meltdowns’

As hair loss and behavioural issues are often associated with nutrient deficiencies and he was a very fussy eater he was prescribed:

  • Children’s multi-vitamin/mineral powder containing a multi-mineral citrate blend for better absorption and alkalinity plus activated B vitamins (2/3 scoop per day).

Unfortunately, loose stools started within the first few days, so his parents were advised to stop supplementation. His stools returned to normal within two days. He then restarted supplementation with resulting multiple loose, smelly bowel movements within first 24 hours.


Follow up: Week 7


His treatment prescription was amended as follows:

  • Gut Repair Powder, 1/3 scoop with glutamine, curcumin, broccoli sprout and digestive enzymes
  • Barrier Probiotic Sachets: containing: B. bifidum W23, B. lactis W51, B. lactis W52, L. acidophilus W31, L. brevis W63, L. casei W56, L. salivarius W24, L. lactis W19, L. lactis W58. Dose: 1 sachet/day

Clinical trials have demonstrated this combination of probiotics to improve intestinal barrier function, increase production of interleukin (IL)-10, reduce lipopolysaccharides (LPS), and reduce the risk of gastrointestinal infection.2


Nutripath Complete Microbiome Mapping test revealed:


  • Low-normal secretory IgA (sIgA), indicating reduced mucosal protection/defences.
  • Faecal zonulin creeping towards the top of the reference range, which supports intestinal permeability playing a role in his symptoms.
  • Calprotectin is present so there is a level of inflammation as well.
  • High Dientamoeba potentially contributing to his foul-smelling stools and certainly to general dysbiosis as are the raised Streptococcus species
  • High Citrobacter freundii – is an LPS producer, increased levels have also been found in ASD patients as well as being linked to Rheumatoid Arthritis which is in his family history.
  • High Candida species – increased levels found in autistic children compared to neurotypical subjects
  • High Enterohemorrhagic Escherichia coli (EHEC) - increased levels have been found in ASD patients, it is a pathogen with increased risk for Hemolytic Uremic Syndrome especially if treated with antibiotics and in the under 5 age group. It is also a LPS producer.
  • High Escherichia species – even though it is considered a commensal species is it overgrown
  • Low Lactobacillus species – this is quite common as most lactobacillus are quite transitory
  • Suboptimal short-chain fatty acids (19.9umol/g). Ideally in clinic I like to see short chain fatty acid production between 80-90 umol/g


Follow up: Weeks 9 to 11


Implemented a modified form of Kerry Bone’s Bowel Flora Protocol where we undertook anti-microbial work on the weekends and supported GIT function and beneficial bacteria growth during the week.

Phase 1 - Weed

  • Built up to the full therapeutic dose of Commiphora myrrha (Myrrh) over two weekends. Dose: 1 mL (20 drops) morning and night (with manuka honey to increase compliance)
  • Over the counter worm treatment, repeated at day 14

By week 11 he seemed calmer and in a better mood. His had hair regrowth in the first spot while the second alopecia spot hadn’t increased.


Follow up: Week 17


At this stage, he had completed five weeks of the ‘weed’ herbs before the bottle broke. His mood was noticeably different, happier, and more “joyful”. His imaginative play had increased, and he was ‘talking heaps’ as his speech had improved. He was paying more attention to instructions and able to copy actions. His toilet training was also back on track with formed stools and no undigested food. Overall, his challenging behaviours seemed easier to manage. Previously, the father had been sceptical but was now on board. His paediatrician also noticed and commented on his improvement.

His prescription was amended as follows:

  • Introduced a tasteless, heat stable prebiotic fibre powder (Partially Hydrolysed Guar Gum) to help support beneficial bacteria growth • Shifted to an alternative Gut Repair Powder, 1 scoop daily – glutamine with zinc, vitamins A, D prebiotics and Boswellia serrata to support secretory IgA production as well as barrier function.
  • Introduced Punica granatum (Pomegranate) liquid as a second round of anti-microbial work at 1.5 mL (30 drops) twice a day with Manuka honey


Follow up: Week 21


  • Continued improvements with speech, concentration, mood, and interactions with others. “Typical 3-year-old”
  • Began titrating down the pomegranate liquid
  • Gradually dropped doses over 6 weeks from 2 doses, 3 days a week to 1 x 30 drops once a week for several weeks


Follow up: Week 27 to 32


The patient was happy and comfortable. His hair had grown back, and his talking was non-stop. His eating was still variable, but he was much better at trying new foods and sitting at the table with everyone else. His comprehension had continued to improve, and he was more tolerant of others.

Prescription amendments:

  • Swapped back to Gut Repair Powder, 2/3 tsp once daily as he preferred the taste and digestive enzyme support was still relevant

Retesting stools

There was a longer than an ideal gap between stool retesting and starting the next round of the protocol. The family had left early to go on a travelling holiday to avoid lock downs. All they had with them was a general probiotic and the multi vitamin/mineral powder while he was away. While his hair was completely regrown and he had a growth spurt, he experienced regressions behaviour, toileting and sleep.

Stool Retesting Results:

  • Although they hadn’t stopped eating gluten, anti-gliadin IgA dropped from 47 to <20
  • Secretory IgA improved 736 to 803.9
  • Zonulin was still high
  • Beta-glucuronidase had increased
  • There had been some opportunistic growth with Streptococcus species increasing from 3.8 to 4.5
  • Resolved - Dientamoeba fragilis, Citrobacter species, EHEC, and Aeromonas species
  • Decreased – Citrobacter freundii, Candida species, Staphylococcus species, and Methanobacteraciaceae
  • Increased – Streptococcus species, opportunistic species (Bacillus species, Enterococcus faecalis, Enterococcus faecium, Morganella species, Fusobacterium)
  • Beneficial bacteria have increased except for Faecalibacterium prausnizii
  • Short-chain fatty acid production has increased substantially from 19.9 to the 83.3 so even though the percentage of butyrate has dropped from 30.3 to 26.7, the overall amount being produced is significantly higher.

Phase 2 – Feed and Seed

Prescription

  • Hypoallergenic Gut Repair Powder, ½ flat tsp BD (glutamine powder with zinc carnosine, acacia gum and slippery elm) for additional prebiotics
  • Barrier Probiotic Sachets, 1 sachet/day
  • Probiotic – L. rhamnosus GR-1 and L. ruteri RC-14 – 1 capsule per day
  • Partially hydrolysed guar gum ½-1 teaspoon per day + prebiotics in the diet
  • Calcium D-glucarate – 1/8th teaspoon twice daily
  • E. coli Nissle 1917 – 1 capsule per day

Anti-microbial liquid herb mix

  • Thymus vulgaris (Thyme) 15 mL
  • Glycyrrhiza glabra (Licorice) 15 mL
  • Juniperus communis (Juniper Berry) 20 mL
  • Punica granatum (Pomegranate) 50 mL
  • Dose: 2 mL, 3 times/day, 3 days/week (they did 3mls twice daily on childcare days)


Follow up: Week 47


Delays in treatment had seen regression in symptoms prior to reintroducing anti-microbial herbs. Post treatment:

  • Behaviours, toileting and sleep had all improved again
  • Still struggling with taste and textures
  • Alopecia spots had completely regrown
  • Slowly titrated down the herbs and supplements (maintained probiotics daily for 3 months post end of anti-microbials)


Final follow up


  • Moods are great, sleeping well. Dinner time has improved “a lot”
  • Improved so much with therapies he is preparing for school next year
  • One alopecia spot has returned but still hasn’t had any blood tests undertaken to check for nutrient deficiencies
  • Intermittently using the children’s multi-mineral/multi-vitamin powder


Clinical Thoughts


In the past I’ve probably fallen into thinking about the impact of LPS on intestinal permeability and not considered its direct impact on mood and cognitive function. This case highlighted the importance of having a gut-brain axis focus when working with patients, especially neurodivergent patients. There was a clear correlation between his gut function and improvements (and declines) in mood and cognition. Barrier function is still a vital component but focusing treatment on the species driving LPS production drove clear improvements. As we deepen our understanding of nutritional and herbal interventions this is a space where we have the potential to achieve fantastic results, especially in those instances where antibiotics are not an option such as EHEC overgrowths.

“Our 3 ½ year old son was having a lot of behavioural and sensory issues with very delayed speech…. Significantly increased mood, calmer, less frustrated, improved concentration, healthier bowel habits and improved appetite.… Our speech pathologist couldn’t believe the difference. AND my husband is now a fan!”


References


1. Xu M, Xu X, Li J, Li F. Association between gut microbiota and autism spectrum disorder: a systematic review and meta-analysis. Frontiers in psychiatry. 2019 Jul 17;10:473. 

2. Van Hemert S, Ormel G. Influence of the multispecies probiotic Ecologic® BARRIER on parameters of intestinal barrier function. Food and Nutrition Sciences. 2014 Sep 22;5(18):1739






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