





































Berkeley
Pharma Tech
Journal of Medicine

Correspondence: 
mayumimagdalena@gmail.com

Keywords:
Gut Microbiome                   
Autism Spectrum Disorder 
Neurodevelopment                   
Gut-Brain-Axis                  
Dysbiosis
Microbiota Transfer Therapy 
Blood-Brain-Barrier

Submitted August 11, 2023 
Accepted March 15, 2024
Published June 28, 2024

Full Open Access

Creative Commons Attribution 
License 4.0

Abstract
The gut microbiome, a diverse community of microorganisms in the gastrointestinal 
tract, is vital for human health and has a symbiotic relationship with the host. Autism 
spectrum disorder (ASD), a complex condition affecting social interaction, speech, and 
behavior, manifests early in life and affects 1 in 36 children globally. Research shows a 
significant link between the gut microbiome and ASD symptoms, with dysbiosis 
observed in individuals with ASD compared to neurotypical populations. Pathogenic 
gut microbiota can produce toxins that increase gut permeability, impair the 
intestinal barrier, and activate the immune system. The vagal nerve, influencing 
central nervous system (CNS) activity, can release peripheral cytokines inducing 
depression-like behaviors. Thus, dietary changes and treatments targeting the gut 
microbiota, such as Microbiota Transfer Therapy (MTT), offer promising methods for 
treating ASD symptoms. Current research focuses on dietary therapies like gluten-free 
and casein-free diets, ketogenic diets, and probiotics/prebiotics supplementation to 
modify the gut microbiota and enhance ASD treatment outcomes. However, more 
research is needed to fully understand the gut microbiota-ASD connection and 
establish evidence-based interventions. Individualized approaches are crucial for the 
safety and effectiveness of therapeutic strategies for ASD. Exploring the gut 
microbiome's role in ASD offers promising avenues for novel treatments and improved 
understanding of the disorder.

Exploring the Gut Microbiome-Autism 
Spectrum Disorder Connection: 
Implications for Therapeutic 
Interventions and Future Directions 
By: Mayumi Schaepers-Cheu, Mansi Patel, Gizell Lien, Amaaya Arora



1. Introduction

Autism Spectrum Disorder (ASD) is a complex developmental disability 
characterized by distinct neurobiological variations in the brain.1 While the 
exact causes of ASD are not yet fully understood, some cases are associated 
with speci�c genetic conditions. ASD is characterized by a diverse array of 
behavioral and developmental symptoms, which typically manifest early in 
childhood, often before the age of three years. The term "spectrum" 
encapsulates the wide range of symptoms and the varying degrees of 
impairment that individuals with ASD may exhibit, making each case 
unique with its own set of challenges and strengths. Two primary 
categories of symptoms are commonly observed in individuals with ASD: 
di�culties in social communication and engagement, and the presence of 
restricted and repetitive behaviors.2 In the realm of social communication, 
individuals with ASD often struggle to interpret and respond to social 
cues, which can include challenges in maintaining eye contact, recognizing 
facial expressions, and understanding nonverbal gestures.2 These di�culties 
can hinder their ability to initiate and maintain meaningful interactions 
with others, leading to potential feelings of isolation and social disconnect. 
Additionally, individuals with ASD may exhibit a wide array of restricted 
and repetitive behaviors.2 These behaviors can manifest as repetitive 
movements, such as hand-�apping or body-rocking, intense and narrow 
interests in speci�c topics or objects, and a strong preference for adhering 
to rigid routines.2 These behaviors may serve as coping mechanisms for 
individuals with ASD, providing them with a sense of comfort and 
predictability in an otherwise overwhelming world. It is crucial to recognize 
that ASD is a spectrum disorder, encompassing a broad range of symptoms 
and levels of functioning.4 Some individuals with ASD may have 
exceptional abilities in certain areas, often referred to as "splinter skills," 
while facing signi�cant challenges in others. The degree of impairment can 
vary widely, and early intervention, therapy, and support can play a crucial 
role in fostering developmental progress and enhancing the quality of life 
for individuals with ASD. As the understanding of the disorder continues 
to evolve, ongoing research e�orts are working to elucidate the underlying 
causes and identify e�ective interventions. By recognizing and embracing 
the unique strengths and challenges of each individual with ASD, it is 

Berkeley Pharma Tech Journal of Medicine | 35



possible to foster a more inclusive and compassionate society that promotes 
understanding for all. 

Due to its impact on health and disease, the human gut microbiome is a 
dynamic and complex ecosystem that has attracted signi�cant interest. 
Numerous studies have shown that the biome plays an important role in a 
wide range of physiological functions, including immunological, 
metabolic, nutrition, and even neurological function. The gut microbiome 
is a colony of trillions of bacteria, viruses, fungi, and other microbes. The 
most prevalent and well-studied of the microbes are bacteria. However, due 
to a complex interaction of variables including genetics, nutrition, age, 
geography, lifestyle, and exposure to environmental e�ects, the variety and 
relative abundance of microbial species can di�er signi�cantly from one 
person to another. In a symbiotic connection with the human host, the gut 
microbiome plays a crucial part in digestion and nutritional absorption. It 
allows for the breaking down of �bers and complex carbohydrates that our 
systems cannot digest on their own, which supports energy absorption and 
the creation of nutrients and vitamins. Additionally, the gut microbiome 
supports a healthy immune system by defending against dangerous 
infections and fostering immunological tolerance to advantageous 
microbes and food antigens.14  A bidirectional communication connection 
between the gut and the brain has been revealed by recent studies, which 
have also given light on the gut brain axis (GBA) (Figure 1). The gut 
microbiota can a�ect not only physical health but also mental health and 
cognitive performance, according to this complex connection. Changes in 
the gut microbiota have been linked to a number of neurological and 
psychiatric illnesses, including anxiety, ASD, and depressive and phobic 
disorders.15 However, dysbiosis—disturbances in the delicate equilibrium 
of the gut microbiome—have been connected to a variety of health issues 
and disease states. Antibiotic usage, dietary changes, infections, stress, and 
other environmental e�ects are some factors that may cause dysbiosis. 
Dysbiosis itself can result in in�ammation, metabolic problems, and an 
elevated risk of infection  ( Figure 3). Therefore, the gut microbiome plays a 
crucial role in human health, explaining the growing interest in researching 
therapeutic approaches that target the gut microbiota to enhance general 
health and treat a variety of medical diseases.12  Healthy gut microbiota can 

Berkeley Pharma Tech Journal of Medicine | 36



be restored and maintained through a variety of methods, including 
probiotic supplementation, prebiotic intake, and dietary changes. It is 
expected that as research on the gut microbiome develops, so will 
understanding of how the biome a�ects human health and disease. 
Utilizing this knowledge can result in cutting-edge customized medicine 
strategies and the creation of targeted medicines to treat a variety of health 
issues related to dysbiosis, opening up a promising, new area for enhancing 
human health and well-being. 

The central and enteric nerve systems communicate in both directions 
through the GBA, which connects the brain’s emotional and cognitive 
regions to peripheral intestine processes (Figure 1). The GBA is a complex 
and dynamic network of communication that is extremely important in 
controlling di�erent facets of our physical and mental health (Figure 1). 
The investigation of the connection between the gut microbiome and ASD 
is driven by several compelling rationales. Each highlights the potential 
signi�cance of the GBA and its impact on neurodevelopment and behavior 
in individuals with ASD. A high proportion of individuals with ASD 
experience gastrointestinal (GI) issues, such as chronic constipation, 
diarrhea, abdominal pain, and in�ammation. These GI disturbances 
suggest a potential connection between gut health and ASD, prompting 
investigations into the role of the gut microbiome in contributing to or 
exacerbating these symptoms. Studies have revealed that individuals with 
ASD often exhibit alterations in the composition and diversity of their gut 
microbiota compared to neurotypical individuals.11 These di�erences have 
sparked curiosity about whether these changes could in�uence ASD 
symptoms. The gut microbiome is known to in�uence neurodevelopment 
and brain function through its impact on neurotransmitters and immune 
responses3 (Figure 1). Given the neurological and behavioral nature of 
ASD, exploring the potential link between the gut microbiome and ASD 
has become a signi�cant area of interest and could pave the way for 
personalized therapeutic strategies.3 If speci�c gut microbiome patterns 
and biomarkers are associated with certain ASD symptoms, it could lead to 
targeted interventions tailored to individual needs, potentially improving 
treatment outcomes.3 The emerging research in this �eld holds promise for 

Berkeley Pharma Tech Journal of Medicine | 37



developing more e�ective and individualized therapies for individuals with 
ASD, providing new avenues for enhancing their health and quality of life.

2. Gut Microbiome in ASD

The GBA is a bidirectional communication network that links the CNS 
with the enteric nervous system (ENS) of the gastrointestinal (GI) tract 
(Figure 1). This sophisticated and dynamic axis plays a crucial role in 
regulating various aspects of our physical and mental health. The GBA’s 
relevance to ASD has garnered increasing attention in recent years.8

Figure 1: Gut-Brain Axis Communication Network

Many individuals with ASD also experience GI disturbances, such 
as chronic constipation, diarrhea, and in�ammation, suggesting a 
potential link between gut health and ASD. The gut microbiota, 
a crucial component of the GBA, plays a signi�cant role in 
modulating brain function and behavior through the production of 
neurotransmitters, microbial metabolites, and immune signaling 
molecules.14 This suggests that disruptions in the gut microbiome could 
in�uence neurodevelopment. The GBA is involved in the 
regulation of immune responses, in�ammation, and neural signaling, 
which are all processes implicated in ASD pathogenesis.9 The 
bidirectional communication between the gut and the brain can impact 
neurodevelopmental processes, social behaviors, and cognitive functions, 
which are frequently a�ected in individuals with ASD.1 

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Understanding the relevance of the GBA to ASD holds immense potential 
for the development of new therapeutic strategies. Targeting the gut 
microbiome through interventions like probiotics, prebiotics, and 
dietary modi�cations may o�er novel approaches to managing 
ASD-related symptoms and improve the overall well-being of 
a�ected individuals. Overall, the GBA represents a complex and 
promising area of research in the context of ASD. Investigating the 
interactions between the gut microbiota and the CNS may pave the 
way for innovative treatments and personalized interventions.15 

Figure 2: Blood-Brain-Barrier and Gastrointestinal Barrier 

Two separate physiological barriers in the human body, the blood-brain 
barrier (BBB) and the GI barrier, play crucial, protective roles (see Figure 
2). The intestinal mucosa is where the intestinal barrier is in the digestive 
system.5 It controls the entry of bene�cial molecules, poisons, and 

Berkeley Pharma Tech Journal of Medicine | 39



pathogens into the body while regulating the transit of nutrients and water, 
among other molecules, into the bloodstream.5 The lining consists of 
mucous membranes that trap hazardous chemicals, epithelial cells that 
provide a protective barrier, and tight junctions that close cell gaps. The 
intestinal barrier supports immune defense, promotes nutrition 
absorption, and preserves healthy gut microbiota.5 Moreover, the BBB is a 
highly selective protective barrier that regulates the passage of substances 
between the bloodstream and the brain tissue to maintain a stable and 
controlled environment within the CNS.7 Endothelial cells, astrocytes, and 
pericytes play a role in maintaining the integrity of this barrier, which 
safeguards the brain by controlling the passage of chemicals across the 
BBB.7 The BBB protects the brain from toxins and keeps the brain's 
environment steady for healthy neuronal activity.7 It may, however, make it 
more di�cult to transport medications to the brain. The intricacy of the 
body's defense mechanisms is shown by the importance of both barriers for 
maintaining general health and protecting the brain from harm. 
Unidenti�ed Erysipelotrichaceae, Faecalibacterium, and Lachnospiraceae 
have been shown to be positively linked with ASD severity.10 Notably, three 
microbial indicators (Faecalitalea, Caproiciproducens, and Collinsella) were 
found in a random forest model as potential biomarkers that distinguish 
between healthy controls and individuals with ASD based on gut 
microbiome pro�les. This current study provides evidence for a link 
between gut microbiota and ASD, with the data implying that gut 
microbiota may play a role in symptomatology.15 As a result, modulating 
the gut microbiome can serve as a novel therapeutic method for ASD.10

3. Mechanism of the Gut Microbiome and ASD

Certain compounds have been the center of attention in studies aiming to 
uncover a correlation between the gut microbiome and the onset of ASD. 
Vast amounts of evidence connecting changes of maternal gut microbiome 
pro�les to the di�erences present in brain development patterns of 
o�spring have been found through experimental methods.16 Speci�cally, 
research involving the in�uence of Cesarean section deliveries, and the use 
of mice as animal models, hint at these links.17 Multiple studies have found 

Berkeley Pharma Tech Journal of Medicine | 40



that newborns delivered through Cesarean sections have a higher risk of 
developing ASD in their lifetime.16 Since it has been proven that the 
composition of the microbiota is di�erent amongst newborns delivered 
through a vaginal delivery compared to those born through Cesarean 
delivery, the in�uence of the microbiota is a potential theory for the 
development of ASD.17 This theory is strongly supported by the fact that 
70-80% of individuals with ASD experience GI symptoms (constipation,
bloating, diarrhea, and nausea, among others).18

Multiple theories relating the e�ects of maternal microbiome environments 
on fetus’ development have also been studied with mice. One particular 
study focused on brain metabolomic pro�les and gene expression.4 This 
study demonstrated that mice that were induced with maternal obesity 
factors (EX) produced o�spring with social behavioral de�cits linked to the 
mesolimbic reward system.19 Moreover, subsequent transfer of gut biome 
from the study’s control mice into the o�spring of the induced mothers 
completely corrected these de�cits.19  Thus, this was a clear sign that the gut 
microbiome played a signi�cant role in in�uencing the 
neurodevelopmental pathways of o�spring, and that it can be in�uenced 
by the surrounding mother’s gut biome.19,20

3.1 E�ect of  Short-Chain Fatty Acids on Neurodevelopment

Short-Chain Fatty Acids (SCFAs), primarily acetate, propionate and 
butyrate, have been found to play a role in the development of ASD. 
SCFAs are produced by the breakdown of dietary carbohydrates and amino 
acids.21,22 To study whether there is a clear di�erence in the level of 
microbiome SCFAs in individuals with ASD compared to individuals 
without ASD, Wang et al. analyzed concentrations of SCFAs in 
participants’ fecal samples. To prevent diet from interrupting results as a 
confounding variable, all subjects were given similar diets with equivalent 
amounts of protein, sugar, starch, and �ber.21 It was found that the total 
SCFA (primarily propionic acid, acetic acid, and butyric acid) 
concentration was signi�cantly higher in the ASD group (136.6 mmol/kg 
compared to 111.1 mmol/kg).21 Providing further evidence for the role of 
altered SCFA levels on the onset of ASD-like symptoms, studies with rats 
have shown that the administration of propionic acid induced ASD-like 

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behaviors and produced neuropathological changes reported with ASD in 
the rats.21 Moreover, the previous studies have discovered that increased 
intestinal permeability is reported in ASD cases. Since acetic acid is 
suggested to play a role in the gut epithelial layer, there is a link that has 
appeared between the altered acetic acid levels and ASD symptoms.21,22 
Subsequent analysis also found that ammonia levels were highly elevated in 
the fecal samples of those with ASD compared to the samples of those 
without ASD (42.7 mmol/kg compared to 32.3 mmol/kg).21 Thus, this 
study indicates that there is a clear elevation in these microbiome 
compounds in individuals with ASD, emphasizing an association between 
the onset of ASD and altered microbiome SCFAs.

3.2 E�ect of Lipopolysaccharides on Neurodevelopment

Another focus of scientists working to establish the link between the 
microgut and the onset of ASD is lipopolysaccharides (LPS), an endotoxin 
that can mimic a gram-negative bacteria infection.23 A study using Wistar 
rats between the age of 12 and 14 weeks highlighted the speci�c e�ects of 
induced LPS solution in the pregnant rats.23 Although this research group 
previously found that prenatal exposure to LPS induces behaviors similar 
to those caused by ASD. These symptoms were measured with T-maze 
spontaneous alternation tests, which were impaired in mice that had 
prenatal LPS exposure.23,24,25 These tests are designed to measure social 
de�cits, repetitive behaviors, and cognitive in�exibility in the 
ASD-context.23,24,25 In addition to these results, the researchers identi�ed 
reduced maternal levels of magnesium, selenium, manganese, and zinc 
following inducement of LPS.8 More interestingly, prenatal zinc treatment 
prevented o�spring from demonstrating such autistic-like behaviors.23,24,25 
A follow-up study by the same group of researchers illustrated the immune 
and in�ammatory e�ects of lowered LPS.23 LPS was shown to signi�cantly 
increase the production of proin�ammatory cytokines in the o�spring.23 
These cytokines sequestered zinc and caused maternal as well as fetal 
hypozincemia.23 Another study highlights a theory for the alteration of 
lipopolysaccharide (LPS) levels within the biome of individuals with ASD 
by demonstrating that 36.7% of children with ASD exhibit modi�ed 
intestinal permeability, a marked contrast to the change observed in less 
than 5% of non-ASD children.26

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3.3 E�ect of Serotonin on Neurodevelopment

Serotonin has also been shown to be associated with the development of 
ASD due its connection with the gut-microbiome axis.27,28 The fact that 
serotonin is observed to have intense activity during the early stages of 
development gives the neurotransmitter great importance when discussing 
neurodevelopmental disorders.28 SCFAs are able to cross the BBB and 
modulate the production of serotonin, in�uencing early brain 
development.29 About 90% of serotonin in the body is produced by 
enterochroma�n cells in the GI epithelium. Therefore, alterations in the 
gut microbiome can result in the deregulation and changes in serotonin 
production. The main mechanism through which serotonin can play a role 
in mediating ASD-symptoms is by acting as a pro-in�ammatory molecule. 
Goeden et al. discovered that increasing maternal in�ammation midway 
during pregnancy results in an upregulation of placental tryptophan 
(TRP) metabolism.30 Since TRP is converted into serotonin, there is 
increased serotonin present in the fetal forebrain, linking the maternal 
microbiome composition to the fetal biome, disrupting some 
serotonin-dependent neurodevelopmental processes.30 Mild immune 
activation in the dams used in the study also presented similar results of 
increased serotonin in the fetal forebrain.30 This study o�ers a strong 
direction for uncovering the speci�c mechanisms through which serotonin 
in�uences fetal brain development in the early stages of life. Positron 
emission tomography (PET) and post mortem studies also indicate that the 
pattern of serotonin synthesis in non autistic children resembles closely 
with the pro�le of synaptic density in their frontal cortex, revealing a 
somewhat global abnormality of serotonin synthesis and synaptogenesis.28 
Lastly, the processes of high brain serotonin synthesis and synaptogenesis 
during the preschool years has been shown to be highly disrupted in 
autistic children.28

Although serotonin serves as a vital link between the gut microbiome and 
the development of ASD, abnormal levels of other metabolites are 
associated with ASD-like symptoms.31 Mass spectrometry studies have 
enabled the observation of the gut composition as a whole, revealing 
di�erences in steroid hormones between individuals with and without 

Berkeley Pharma Tech Journal of Medicine | 43



ASD.31,32 Speci�cally, many metabolites within the pregnenolone and 
androgen pathways were found to be elevated in individuals with ASD.32 
This �nding further demonstrates that pathways of downstream 
cholesterol metabolism are altered in individuals with ASD.32 Moreover, 
studies have indicated that levels of di�erent metabolites are altered in 
mothers with children born with ASD compared to mothers of children 
without ASD.32,33 Through blood tests, it was found that carnitine 
conjugated molecules were present in lower levels in the mothers with ASD 
children.33 This �nding hints at an underlying mechanism that this 
metabolite takes part in which can a�ect the presence of ASD symptoms. 
In addition to carnitine-conjugated molecules, B12, cis-4decenoylcarnitine, 
catechol sulfate, 7-methylxanthine, and tiglyl carnitine were found to be in 
levels signi�cantly di�erent between both mother groups.33 The results of 
the study’s statistical analysis provides researchers with an idea of how 
changes in a wide variety of microbiome metabolites in�uence a developing 
baby. Instead of focusing on examining the relation of altered levels of one 
molecule, developing methods of analyzing how altered levels of one 
metabolic cell can induce changes in the levels of other molecules can 
provide a more inclusive view on the e�ects of the microbiome on the 
development of ASD.

4. Therapeutic Studies

There is compelling evidence from previously conducted research about a 
link between the gut microbiota and the nervous system. The bi-directional 
GBA includes signaling from the gut microbiota to the brain via neural, 
endocrine, immune, and humoral pathways.34 Bacteria, including 
commensal, probiotic and pathogenic, in the GI tract are involved in the 
activation of neural pathways and CNS signaling systems.35 Emerging data 
support the role of microbiota in in�uencing stress related to anxiety and 
depression disorders. Gut microbial dysbiosis, frequently observed in ASD 
patients, is associated with mood disorders and disruption of the GBA34 
(Figure 3). A large registry based study showed an association between 
increased autism severity with higher probability of having GI problems.36 

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Figure 3: Eubiosis vs. Dysbiosis

4.1 Probiotics and Prebiotics

Probiotic and prebiotic supplements have been proven to improve gut 
health via host-microbe symbiosis and growth/ maintenance of good 
bacteria. Probiotic bacteria and dietary prebiotics can cause distinct 
changes in the composition of the gut microbiota which can improve 
peripheral (gastrointestinal) and central (psychological) symptoms37 
(Figure 3). In the double-blind placebo-controlled study by Schmidt et 
al.,38 forty-�ve healthy volunteers aged 1845 years were administered one of 
two prebiotics (fructooligosaccharides, FOS, or Bimuno® 
galactooligosaccharides, B-GOS) or a placebo (maltodextrin) daily for 3 
weeks. B-GOS intake was shown to signi�cantly reduce salivary cortisol 
awakening response as well as increase processing of positive versus negative 
attentional vigilance as compared with the placebo. This indicates the 
potential of B-GOS supplementation in the treatment of stress-related 
disorders and suggests that it may modulate HPA activity. However, this 
study did not account for gender and no e�ect of prebiotics on subclinical 
anxiety or perceived stress were observed. Another randomized control 
study used a double-blind research method to divide 86 healthy, young 
adults into �ve groups as per colony-forming unit (CFU) and bacterial 
species count to assess the e�ect of probiotics on anxiety and related 
factors.39 The high CFU group reported to have a signi�cant decrease in 
panic anxiety and worry as well an increase in passive a�ect and anxiety 

Berkeley Pharma Tech Journal of Medicine | 45



control compared to the low CFU group. Probiotics were overall observed 
to improve panic anxiety, neurophysiological anxiety, negative a�ect, worry, 
and increase negative mood regulation. This study did not account for a 
diverse and large sample size and was reliant on self reported results, both 
of which posed limitations on the experiment. The use of over-the-counter 
probiotics with di�erent compositions could have also led to skewed 
results. The study by Akkasheh et al.40 included 40 patients, aged 20 to 55 
years, diagnosed with major depressive disorder (MDD) based on DSM-IV 
criteria who were randomized to receive probiotic supplementation for 8 
weeks. Experimental results showed a signi�cant decrease in Beck 
Depression Inventory scores, serum insulin levels, homeostasis model 
assessment of insulin resistance and serum hs-CRP concentrations in 
patients who received the probiotic supplementation as compared with the 
placebo, indicating that probiotic administration can have bene�cial e�ects 
for MDD patients. The study’s limitations include a relatively short 
duration of intervention and insu�cient information about the speci�c 
bacterial strain responsible for the treatment results. 

4.2 Gluten 

Imbalance in the gut microbiota is a common occurrence in individuals 
diagnosed with ASD. Incompletely digested peptides acting as opioid 
agonists have been hypothesized to cross the BBB by entering the 
bloodstream.41 Accumulation of these peptides a�ects brain function, 
speci�cally brain maturation, social communication, and learning, and can 
reduce pain sensitivity while increasing the severity of autism related 
behaviors.42 Elimination diets, particularly a gluten-free casein free (GFCF) 
diet, have been adopted to serve as an alternative treatment of ASD. A 
parental report of strict diet implementation involving the elimination of 
all foods containing gluten and casein has shown to be associated with an 
improvement of ASD behavior, physiological symptoms and social 
behaviors as compared to partial elimination interventions.43 Parents who 
implemented this diet for more than 6 months reported greater 
improvements in ASD behavior and symptoms as compared with a lesser 
implementation duration. These �ndings suggest that strict adoption, 
compliance, and length of diet implementation are all important factors in 
optimizing the e�ectiveness of GFCF diet in children with ASD. In a study 
by Knivsberg et al.,44 15 children with ASD were recommended dietary 

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interventions due to pathological urine patterns. The experiment reported 
that the GFCF diet helped reduce urinary peptide levels, indicating a 
reduction of opioid e�ects, which corresponded with an improvement in 
autistic behaviors, and non-verbal, cognitive and motor issues. However, it 
is important to consider the role of a placebo e�ect in this study due to the 
absence of a control group. Another randomized, controlled clinical trial 
found that a GFCF diet has a signi�cant bene�cial e�ect on autistic and 
related behaviors of prepubescent ASD patients at 8, 12 and 24 months of 
diet intervention.45 These results imply that adoption of the GFCF diet can 
have a positive e�ect on the developmental outcome for some children with 
ASD. The exclusion of a double-blind or placebo factor may have posed 
limitations on this study. 

The nutritional de�ciencies that could arise from the GFCF diet are an area 
of high concern. Long-term implementation of such dietary interventions 
can cause a lack of proper supplementation that could have adverse e�ects 
on bone health. Children with ASD commonly have picky eating behaviors 
associated with speci�c taste, colors or appearances of food due to which it 
is relatively di�cult to implement nutrition plans with adequate macro and 
micronutrients.46 This can cause the implementation of a speci�c diet such 
as GFCF to become even more di�cult. The high healthcare costs 
associated with this diet could also place a burden on the families. To 
overcome such challenges, appropriate nutrition plans should be curated 
for children with ASD and the families should be provided with proper 
information and training. 

Fecal microbiota transplantation (FMT) has also been identi�ed as a 
potential therapeutic approach to treat ASD (see Figure 4). FMT can be 
used to change the composition of the gut microbiota and improve GI and 
neurobehavioral symptoms in ASD patients.47  The fermentation of 
undigested food along with the production of bioactive compounds like 
SCFAs can a�ect the health of the large bowel.45 Protein fermentation 
by-products can also severely impact host health by increasing 
in�ammatory response, tissue permeability, and colitis severity in the gut.48 
In a study by Wang et al.,49 researchers found higher fecal concentrations of 
large bowel fermentation products, speci�cally SCFAs and ammonia, in 
children with ASD as compared with controls. Since these fermentation 

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products can impact the health of the large bowel, the observed higher 
concentrations could be a reason for alterations in GI health and function 
in ASD patients.49 A clinical trial evaluating the e�cacy of FMT in ASD 
patients performed FMT by fecal and oral routes in ASD children 
experiencing GI disorders.50 Although the study was limited by a lack of a 
control group and the use of participants from the same geographical 
location, the results demonstrated that FMT could improve GI symptoms 
and autism related behaviors while signi�cantly changing the serum levels 
of neurotransmitters.50  

5. Microbiota Transfer Therapy

MTT, a modi�ed FMT protocol, has emerged as a viable treatment option 
for ASD. A shotgun metagenomics study showed that the relative 
abundance of �ber consuming, and bene�cial microbes increased after 10 
weeks of MTT in children with ASD, thereby normalizing levels that were 
relatively low as compared with typically developing (TD) children.51 The 
�ndings also indicated that MTT leads to an initial improvement in the 
metabolic pro�les of children with ASD, but that a booster or longer 
treatment time would be required for retention of the bacteria.51 A further 
open-label clinical trial evaluated the impact of MTT on gut microbiota 
composition and GI and ASD symptoms of ASD-diagnosed children52 
which will be later discussed.

In essence, MTT alters a recipient’s current gut microbiome by replacing it 
with a donor’s healthy gut microbiome.53 This is done by transferring fecal 
samples from the donor to the GI tract of the recipient54 (Figure 4). This 
method aims to have therapeutic bene�ts that can target a wide range of 
health issues.53 The knowledge on the scope of MTT e�cacy and safety is, 
however, limited due to it being a newly emerging therapy.55 

Studies have been fully executed to test whether MTT can alleviate ASD 
symptoms, as MTT has already been tested with other psychiatric 
diseases.56 There is foundational evidence that MTT should aid in 
alleviating ASD symptoms, as children with ASD have GI problems or gut 
microbiota related issues, such as bloating and constipation.56 The gut 

Berkeley Pharma Tech Journal of Medicine | 48



microbiome is also vastly di�erent in children with ASD, as they have less 
bene�cial bacteria like Bifidobacterium spp., and instead, greater amounts 
of pathogenic bacteria, such as Desulfovibrio and Clostridium.56

Figure 4: Fecal Transplant Therapy Methodology

One foundational study examined the e�ects of MTT on fecal metabolite 
pro�les of children with ASD and GI symptoms, in comparison to 
children that are TD.57 The researchers analyzed 669 biochemical 
compounds in the children before, during, and after MTT. They found 
that fecal metabolite pro�les of the ASD group became more similar to the 
TD group after treatment, suggesting the positive impact of MTT on fecal 
metabolites.57 In another clinical trial, MTT was used with 18 children 
with ASD and resulted in a signi�cant reduction (approximately 80%) in 
GI symptoms. This persisted for 8 weeks after treatment and behavioral 
ASD symptoms also improved and remained after treatment.52 In addition, 
the microbiota of the donors appeared to be at least partially engrafted in 
the recipients which helped to shift the gut microbiota of children with 
ASD towards that of TD children. However, this study was limited as it 
had a small sample size and was also not placebo controlled, blinded, or 
randomized. A similar study in China also found FMT therapy to improve 
GI issues, ASD symptoms, and serum neurotransmitter levels after an 
8-week follow-up.47

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In terms of greater long-term e�ects, there are minimal studies and still 
much to uncover. However, one study followed up with 18 participants 
with ASD two years after MTT therapy.58 The improvements in GI 
symptoms and autism-related symptoms observed during the initial 
treatment were largely maintained and even improved after the treatment 
ended.58 The study also found persistent positive changes in the gut 
microbiota, including increased bacterial diversity and the increases of 
bene�cial bacteria abundance, such as for Bifidobacteria and Prevotell.58

There are also two prevalent ongoing clinical trials, as well, exploring FMT 
as an e�ective long term therapy. One of the trials, estimated to be 
completed in 2024, focuses on children with ASD and GI issues. In this 
trial, some children receive MTT treatment, while others are assigned to a 
placebo group to compare the e�ectiveness in alleviating GI symptoms and 
managing ASD symptoms.52 Another trial to be completed in 2024 follows 
the same methodology, but with adults with ASD and GI issues. They will 
undergo oral administration of full spectrum microbiota for a speci�ed 
duration to understand longer lasting implications of MTT as a therapy.59

MTT or FMT as a therapy has side e�ects and limitations. In general, it is 
safe, however, it can also lead to side e�ects such as GI discomfort, 
vomiting, nausea, diarrhea, and spotty stools.54 A study with a two-year 
follow-up shows the safety of FMT in reducing GI and neurobehavioral 
symptoms in children with ASD. No adverse side e�ects associated with 
FMT were found, suggesting its overall safety in both the short and 
long-term.47

The implementation of treatments such as FMT and MTT in clinical 
settings involves navigating various challenges and opportunities for 
standardization and personalization. Barriers to standardization include 
regulatory hurdles, donor variability, and the need to establish consistent 
treatment protocols while ensuring e�cacy and safety. [GR1] 
Personalization strategies for these treatments involve microbiome pro�ling 
to tailor interventions based on individual patient characteristics, 
stratifying patients for personalized treatment selection, and implementing 
follow-up monitoring to adjust treatment protocols over time. 

Berkeley Pharma Tech Journal of Medicine | 50



To understand the limitations of MTT more speci�cally, further studies are 
needed to clarify the exact contributions of each factor in MTT to gut 
microbiota changes in ASD. Many of the previously mentioned studies 
include a mixed group of participants with various GI issues, and a more 
homogeneous test group is needed.60 The open-label design of some studies 
also introduces potential placebo e�ects and longer observation periods in 
future trials would enhance the understanding of long-term safety and 
bene�ts.60

6. Future Directions and Implications

So far, it has been established that gut microbiota imbalances have been 
observed in individuals with ASD and other psychiatric disorders61. The 
gut microbiome a�ects the production of speci�c molecules, immune 
function, and GI integrity, all in�uencing ASD, and all areas where 
therapies can be developed.62 

For the future, ASD research and therapies are centered around 
microbial-mediated therapies, including probiotic therapy, prebiotic 
supplementation, and FMT.63 These therapies have growing potential in 
addressing ASD symptoms and GI issues that commonly supplement 
ASD.62,63 FMT therapy is gaining substantial acceptance, although there are 
concerns on long term impacts, standardization and infection.63 Due to 
these concerns, synthetic stool samples are being researched, which consist 
of predetermined bacterial populations and could be customized to 
enhance the personalized therapy's e�cacy.64

Personalized dietary treatments, based on the gut-immune-endocrine-brain 
axis, have also been explored.64 These methods consider dietary factors, 
immune responses, hormonal regulation, and brain function 
connections.65 By screening for in�ammatory responses to dietary proteins 
such as gluten and casein, health care providers can construct 
patient-speci�c dietary plans.16 These diets can be used in tandem with 
prebiotic or probiotic supplements to restore a healthy gut microbial 
balance, thereby alleviating ASD symptoms.65,66 Various studies have shown 
that speci�c bacterial strains, such as those of Bacteroides fragilis and 

Berkeley Pharma Tech Journal of Medicine | 51



lactobacillus species, hold potential in reversing autistic behaviors and 
improving GI symptoms in both mouse models and autistic children. 
However, further research is necessary to optimize the formulations.66

Biomarkers have also served to assess the implementation of probiotic 
supplementation.13 Microbiota composition and in�ammatory markers 
can demonstrate how to improve GI issues and thus how to manage ASD 
symptoms. This is also a non-invasive diagnostic tool for ASD that may be 
developed more and can serve as early intervention and prevention 
strategies. Both single strain and multi-strain probiotics have been e�ective 
in modulating these biomarkers and these �ndings highlight 
biomarker-guided probiotic therapy as a future option for managing 
ASD.13 

These approaches show potential in improving both GI symptoms and 
behavioral irregularities of ASD. However, further research, 
standardization of procedures, and optimization of treatment regimens are 
necessary to fully evaluate their long-term e�ectiveness.63

7. Conclusion

The research on the gut microbiome-ASD connection has provided 
valuable insights into the way mechanisms of the gut and brain intertwine. 
Numerous studies have consistently shown di�erences in the gut 
microbiomes of individuals with ASD, characterized by dysbiosis and 
reduced microbial diversity.12,34,61 The discovery of gut-brain 
communication pathways has further underscored the relevance of these 
microbial communities in in�uencing brain development and ASD 
symptoms.14,15,34 These �ndings highlight the importance of ongoing 
research in this �eld, as discoveries may pave the way for novel and targeted 
treatments that leverage the gut microbiome to manage ASD more 
e�ectively. By exploring the intricate relationship between the gut 
microbiome and ASD, researchers can aim to unlock promising therapeutic 
avenues that could improve the quality of life for individuals living with 
these complex neurodevelopmental disorders. 

Berkeley Pharma Tech Journal of Medicine | 52



References

1. Fattorusso A, Di Genova L, Dell'Isola GB,
Mencaroni E, Esposito S. Autism Spectrum
Disorders and the GutMicrobiota.Nutrients.
2019 Feb 28;11(3):521. Doi:
10.3390/nu11030521. PMID: 30823414;
PMCID: PMC6471505.

2. Garcia-Gutierrez E, Narbad A, Rodríguez JM.
Autism SpectrumDisorder AssociatedWith Gut
Microbiota at Immune, Metabolomic, and Neuroactive
Level. Front Neurosci. 2020 Oct 8;14:578666. doi:
10.3389/fnins.2020.578666. PMID: 33117122;
PMCID: PMC7578228.

3. Osadchiy V, Martin CR,Mayer EA. The Gut-Brain
Axis and the Microbiome: Mechanisms and Clinical
Implications. Clin Gastroenterol Hepatol. 2019
Jan;17(2):322332. doi: 10.1016/j.cgh.2018.10.002.
Epub 2018 Oct 4. PMID: 30292888; PMCID:
PMC6999848.

4. Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV,
Bastiaanssen TFS, BoehmeM, CodagnoneMG,
Cussotto S, Fulling C, Golubeva AV, Guzzetta KE,
Jaggar M, LongSmith CM, Lyte JM,Martin JA,
Molinero-Perez A, Moloney G, Morelli E, Morillas E,
O'Connor R, Cruz-Pereira JS, Peterson VL, Rea K,
Ritz NL, Sherwin E, Spichak S, Teichman EM, van de
WouwM, Ventura-Silva AP, Wallace-Fitzsimons SE,
Hyland N, Clarke G, Dinan TG. The
Microbiota-Gut-Brain Axis. Physiol Rev. 2019 Oct
1;99(4):1877-2013. doi: 10.1152/physrev.00018.2018.
PMID: 31460832.

5. ShenoyMD, Indla V, Reddy H. Comprehensive
Management of Autism: Current Evidence. Indian J
PsycholMed. 2017 Nov-Dec;39(6):727-731. Doi:
10.4103/IJPSYM.IJPSYM_272_17. PMID: 29284801;
PMCID: PMC5733418.

6. Bull MJ, Plummer NT. Part 1: The Human Gut

Microbiome in Health and Disease. IntegrMed
(Encinitas). 2014 Dec;13(6):17-22. PMID: 26770121;
PMCID: PMC4566439.

7. Taniya MA, Chung HJ, Al Mamun A, Alam S, Aziz
MA, EmonNU, IslamMM,Hong SS, Podder BR, Ara
Mimi A, Aktar Suchi S, Xiao J. Role of Gut
Microbiome in Autism SpectrumDisorder and Its
Therapeutic Regulation. Front Cell Infect Microbiol.
2022 Jul 22;12:915701. doi:
10.3389/fcimb.2022.915701. PMID: 35937689;
PMCID: PMC9355470.

8. Vancamelbeke M, Vermeire S. The intestinal barrier:
a fundamental role in health and disease. Expert Rev
Gastroenterol Hepatol. 2017 Sep;11(9):821-834. Doi:
10.1080/17474124.2017.1343143. Epub 2017 Jun 26.
PMID: 28650209; PMCID: PMC6104804.

9. Oh D, Cheon KA. Alteration of Gut Microbiota in
Autism SpectrumDisorder: An Overview. Soa
Chongsonyon Chongsin Uihak. 2020 Jul
1;31(3):131-145. doi: 10.5765/jkacap.190039. PMID:
32665757; PMCID: PMC7350540.

10. Forlano R, Mullish BH, Roberts LA, Thursz MR,
Manousou P. The Intestinal Barrier and Its
Dysfunction in Patients withMetabolic Diseases and
Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2022
Jan 8;23(2):662. doi: 10.3390/ijms23020662. PMID:
35054847; PMCID: PMC8775587.

11. Mayer EA, Nance K, Chen S. The Gut-Brain Axis.
Annu RevMed. 2022 Jan 27;73:439453. doi:
10.1146/annurev-med-042320-014032. Epub 2021 Oct
20. PMID: 34669431.

12. Nitschke A, Deonandan R, Konkle AT. The link
between autism spectrum disorder and gut microbiota:
A scoping review. Autism. 2020 Aug;24(6):1328-1344.
Doi: 10.1177/1362361320913364. Epub 2020 Apr 28.
PMID: 32340474.

Berkeley Pharma Tech Journal of Medicine | 53



13. Al-Ayadhi L, Zayed N, Bhat RS,
Moubayed NMS, Al-MuammarMN,
El-Ansary A. The use of biomarkers associated
with leaky gut as a diagnostic tool for early
intervention in autism spectrum disorder: a
systematic review.Gut Pathog. 2021 Sep
13;13(1):54. doi:
10.1186/s13099-021-00448-y. PMID:
34517895; PMCID: PMC8439029.

14. Zhao Y, Wang Y, Meng F, Chen X, Chang
T, Huang H, He F, Zheng Y. Altered Gut
Microbiota as Potential Biomarkers for
Autism SpectrumDisorder in Early
Childhood.Neuroscience. 2023 Jul
15;523:118-131. doi:
10.1016/j.neuroscience.2023.04.029. Epub
2023 Jun 3. PMID: 37271221.

15. Ding X, Xu Y, Zhang X, Zhang L, Duan
G, Song C, Li Z, Yang Y, Wang Y, Wang X,
Zhu C. Gut microbiota changes in patients
with autism spectrum disorders. J Psychiatr
Res. 2020 Oct;129:149-159. doi:
10.1016/j.jpsychires.2020.06.032. Epub 2020
Jul 18. PMID: 32912596.

16. Rutayisire E, Huang K, Liu Y, Tao F. The
mode of delivery a�ects the diversity and
colonization pattern of the gut microbiota
during the �rst year of infants' life: a
systematic review. BMCGastroenterol.
2016;16(1):86. Published 2016 Jul 30.
doi:10.1186/s12876-016-0498-0

17. Al-Zalabani AH, Al-Jabree AH, Zeidan
ZA. Is cesarean section delivery associated
with autism spectrum disorder?.Neurosciences
(Riyadh). 2019;24(1):11-15.
doi:10.17712/nsj.2019.1.20180303

18. Dinan TG, Cryan JF. Gut instincts:
microbiota as a key regulator of brain

development, ageing and neurodegeneration. J
Physiol. 2017;595(2):489-503.
doi:10.1113/JP273106

19. Vuong HE, Pronovost GN,Williams DW,
et al. The maternal microbiome modulates
fetal neurodevelopment in mice.Nature.
2020;586(7828):281-286.
doi:10.1038/s41586020-2745-3

20. Vuong HE, Hsiao EY. Emerging Roles for
the GutMicrobiome in Autism Spectrum
Disorder. Biol Psychiatry. 2017;81(5):411-423.
doi:10.1016/j.biopsych.2016.08.024

21. Wang L, Christophersen CT, SorichMJ,
Gerber JP, Angley MT, ConlonMA. Elevated
fecal short chain fatty acid and ammonia
concentrations in children with autism
spectrum disorder.Dig Dis Sci.
2012;57(8):2096-2102.
doi:10.1007/s10620-012-2167-7

22. MacFabe DF, Rodríguez-Capote K,
Ho�man JE, Franklin AE, MohammadAsef Y,
Taylor AR, Boon F, Cain DP, Kavaliers M,
Possmayer F, Ossenkopp K. ANovel Rodent
Model of Autism: Intraventricular Infusions
of Propionic Acid Increase Locomotor
Activity and Induce Neuroin�ammation and
Oxidative Stress in Discrete Regions of Adult
Rat Brain. Am J Biochem Biotechnol.
2008;4(2):146-166.
doi:10.3844/ajbbsp.2008.146.166

23. Kirsten TB, Chaves-Kirsten GP, Bernardes
S, et al. Lipopolysaccharide Exposure Induces
Maternal Hypozincemia, and Prenatal Zinc
Treatment Prevents Autistic-Like Behaviors
and Disturbances in the Striatal Dopaminergic
and mTOR Systems of O�spring. PLoS One.
2015;10(7):e0134565. Published 2015 Jul 28.
doi:10.1371/journal.pone.0134565

Berkeley Pharma Tech Journal of Medicine | 54



24. Timofeeva OA, Roegge CS, Seidler FJ,
Slotkin TA, Levin ED. Persistent cognitive
alterations in rats after early postnatal
exposure to low doses of the organophosphate
pesticide, diazinon.Neurotoxicol Teratol.
2008;30(1):38-45.
doi:10.1016/j.ntt.2007.10.002

25. Timofeeva OA, Sanders D, Seemann K, et
al. Persistent behavioral alterations in rats
neonatally exposed to low doses of the
organophosphate pesticide, parathion. Brain
Res Bull. 2008;77(6):404-411.
doi:10.1016/j.brainresbull.2008.08.019

26. de Magistris L, Familiari V, Pascotto A, et
al. Alterations of the intestinal barrier in
patients with autism spectrum disorders and
in their �rst-degree relatives. J Pediatr
Gastroenterol Nutr. 2010;51(4):418-424.
doi:10.1097/MPG.0b013e3181dcc4a5

27. Israelyan N, Gross Margolis K. Serotonin
as a link between the gut-brain-microbiome
axis in autism spectrum disorders. Pharmacol
Res. 2019;140:115-120.
doi:10.1016/j.phrs.2018.12.023

28. Zafeiriou DI, Ververi A, Vargiami E. The
serotonergic system: its role in pathogenesis
and early developmental treatment of autism.
Curr Neuropharmacol. 2009;7(2):150-157.
doi:10.2174/157015909788848848

29. Appleton J. The Gut-Brain Axis: In�uence
of Microbiota onMood andMental Health.
IntegrMed (Encinitas). 2018;17(4):28-32.

30. Goeden N, Velasquez J, Arnold KA, et al.
Maternal In�ammation Disrupts Fetal
Neurodevelopment via Increased Placental
Output of Serotonin to the Fetal Brain. J
Neurosci. 2016;36(22):6041-6049.

doi:10.1523/JNEUROSCI.2534-15.2016

31. Dan Z, Mao X, Liu Q, et al. Altered gut
microbial pro�le is associated with abnormal
metabolism activity of Autism Spectrum
Disorder.GutMicrobes. 2020;11(5):1246-
1267. doi:10.1080/19490976.2020.1747329

32. Hollowood-Jones K, Adams JB, Coleman
DM, et al. Altered metabolism of mothers of
young children with Autism Spectrum
Disorder: a case control study. BMC Pediatr.
2020;20:557.
doi:10.1186/s12887-020-02437-7

33. Needham BD, AdameMD, Serena G, et
al. Plasma and Fecal Metabolite Pro�les in
Autism SpectrumDisorder. Biol Psychiatry.
2021;89(5):451-462.
doi:10.1016/j.biopsych.2020.09.025

34. Carabotti M, Scirocco A, Maselli MA,
Severi C. The gut-brain axis: interactions
between enteric microbiota, central and
enteric nervous systems.Ann Gastroenterol.
2015;28(2):203-209. Accessed July 19, 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC4367209/

35. Foster JA, Neufeld KAM. Gut–brain axis:
how the microbiome in�uences anxiety and
depression. Trends in Neurosciences.
2013;36(5):305-312.
doi:10.1016/j.tins.2013.01.005

36. Wang LW, Tancredi DJ, Thomas DW. The
prevalence of gastrointestinal problems in
children across the United States with autism
spectrum disorders from families with
multiple a�ected members. J Dev Behav
Pediatr. 2011;32(5):351-360.
doi:10.1097/DBP.0b013e31821bd06a

Berkeley Pharma Tech Journal of Medicine | 55



37. Saulnier DM, Ringel Y, HeymanMB,
Foster JA, Bercik P, Shulman RJ, et al. The
intestinal microbiome, probiotics and
prebiotics in neurogastroenterology.Gut
Microbes. 2012;4(1):17-27.
doi:10.4161/gmic.22973

38. Schmidt K, Cowen PJ, Harmer CJ,
Tzortzis G, Errington S, Burnet PWJ.
Prebiotic intake reduces the waking cortisol
response and alters emotional bias in healthy
volunteers. Psychopharmacology (Berl).
2015;232(10):1793-1801.
doi:10.1007/s00213-014-3810-0

39. Tran N, ZhebrakM, Yacoub C, Pelletier J,
Hawley D. The gut-brain relationship:
Investigating the e�ect of multispecies
probiotics on anxiety in a randomized
placebocontrolled trial of healthy young
adults. Journal of Affective Disorders.
2019;252:271277.
doi:10.1016/j.jad.2019.04.043

40. Akkasheh G, Kashani-Poor Z,
Tajabadi-Ebrahimi M, et al. Clinical and
metabolic response to probiotic
administration in patients with major
depressive disorder: A randomized,
double-blind, placebo-controlled trial.
Nutrition. 2016;32(3):315-320.
doi:10.1016/j.nut.2015.09.003

41. Reichelt KL, Knivsberg AM, Lind G,
NødlandM. Probable etiology and possible
treatment of childhood autism. Brain
Dysfunction. 1991;4(6):308-319.

42. Baspinar B, Yardimci H. Gluten-Free
Casein-Free Diet for Autism Spectrum
Disorders: Can It Be E�ective in Solving
Behavioural and Gastrointestinal Problems?
Eurasian JMed. 2020;52(3):292-297.

doi:10.5152/eurasianjmed.2020.19230

43. Pennesi CM, Klein LC. E�ectiveness of
the gluten-free, casein-free diet for children
diagnosed with autism spectrum disorder:
Based on parental report.Nutritional
Neuroscience. 2012;15(2):85-91.
doi:10.1179/1476830512Y.0000000003

44. Knivsberg A, Reichelt KL, NødlandM,
Høien T. Autistic Syndromes and Diet: a
follow-up study. Scand J Educ Res.
1995;39(3):223-236.
doi:10.1080/0031383950390304

45. Whiteley P, Haracopos D, Knivsberg AM,
et al. The ScanBrit randomised, controlled,
single-blind study of a gluten- and casein-free
dietary intervention for children with autism
spectrum disorders.Nutr Neurosci.
2010;13(2):87-100.
doi:10.1179/147683010X12611460763922

46. Goday P. WheyWatchers andWheat
Watchers: The Case Against Gluten and
Casein in Autism.Nutrition in Clinical
Practice. 2008;23(6):581-582.
doi:10.1177/0884533608326277

47. Li Y, Wang Y, Zhang T. Fecal Microbiota
Transplantation in Autism Spectrum
Disorder.Neuropsychiatric Disease and
Treatment. 2022;18:2905-2915.
doi:10.2147/NDT.S382571

48. Topping DL, Clifton PM. Short-Chain
Fatty Acids and Human Colonic Function:
Roles of Resistant Starch and Nonstarch
Polysaccharides. Physiol Rev. 2001 Jul
1;81(3):1031-1064. doi:
10.1152/physrev.2001.81.3.1031.
49. Diether NE, Willing BP. Microbial
Fermentation of Dietary Protein: An

Berkeley Pharma Tech Journal of Medicine | 56



Important Factor in Diet–Microbe–Host
Interaction.Microorganisms. 2019;7(1):19.
doi:10.3390/microorganisms7010019

50. Li N, Chen H, Cheng Y, et al. Fecal
Microbiota Transplantation Relieves
Gastrointestinal and Autism Symptoms by
Improving the GutMicrobiota in an
Open-Label Study. Front Cell Infect Microbiol.
2021;11:759435. Accessed July 25, 2023.
https://www.frontiersin.org/articles/10.3389/
fcimb.2021.759435

51. Nirmalkar K, Qureshi F, Kang DW, Hahn
J, Adams JB, Krajmalnik-Brown R. Shotgun
Metagenomics Study Suggests Alteration in
Sulfur Metabolism and Oxidative Stress in
Children with Autism and Improvement after
Microbiota Transfer Therapy. Int J Mol Sci.
2022;23(21):13481.
doi:10.3390/ijms232113481.

52. Kang DW, Adams JB, Gregory AC, et al.
Microbiota Transfer Therapy alters gut
ecosystem and improves gastrointestinal and
autism symptoms: an open-label study.
Microbiome. 2017;5(1):10.
doi:10.1186/s40168-016-0225-7

53. Wang JW, Kuo CH, Kuo FC,Wang YK,
HsuWH, Yu FJ, HuHM, Hsu PI, Wang JY,
WuDC. Fecal microbiota transplantation:
Review and update. J FormosMed Assoc. 2019
Mar;118 Suppl 1:S23-S31. doi:
10.1016/j.jfma.2018.08.011. Epub 2018 Sep
1. PMID: 30181015.

54. Antushevich H. Fecal microbiota
transplantation in disease therapy. Clin Chim
Acta. 2020 Apr;503:90-98. doi:
10.1016/j.cca.2019.12.010. Epub 2020 Jan 20.
PMID: 31968211.

55. Li N, Tian H. [Current research progress
and thinking of fecal microbiota
transplantation for the treatment of
gastrointestinal disorders]. ZhonghuaWei
ChangWai Ke Za Zhi. 2017 Oct
25;20(10):1104-1108. Chinese. PMID:
29130220.

56. Generoso JS, Giridharan VV, Lee J,
Macedo D, Barichello T. The role of the
microbiotagut-brain axis in neuropsychiatric
disorders. Braz J Psychiatry. 2021
May-Jun;43(3):293305. doi:
10.1590/1516-4446-2020-0987. PMID:
32667590; PMCID: PMC8136391.

57. Qureshi F, Adams J, Hanagan K, Kang
DW, Krajmalnik-Brown R, Hahn J.
Multivariate Analysis of Fecal Metabolites
from Children with Autism Spectrum
Disorder and Gastrointestinal Symptoms
before and after Microbiota Transfer Therapy.
J Pers Med. 2020 Oct 2;10(4):152. doi:
10.3390/jpm10040152. PMID: 33023268;
PMCID: PMC7712156.

58. Kang DW, Adams JB, Coleman DM,
Pollard EL, Maldonado J,
McDonough-Means S, Caporaso JG,
Krajmalnik-Brown R. Long-term bene�t of
Microbiota Transfer Therapy on autism
symptoms and gut microbiota. Sci Rep. 2019
Apr 9;9(1):5821. doi:
10.1038/s41598-019-42183-0. PMID:
30967657; PMCID: PMC6456593.

59. Arizona State University. Microbiota
Transfer Therapy for Adults With Autism
SpectrumDisorder (ASD)WhoHave
Gastrointestinal Disorders (MTT-ASD).
ClinicalTrials.gov Identi�er: NCT03408886.
Last Update Posted January 9, 2023.
Accessed July 15, 2023. Available at:

Berkeley Pharma Tech Journal of Medicine | 57



https://clinicaltrials.gov/ct2/show/NCT0340
8886

60. Jung LeeW, Lattimer LD, Stephen S,
BorumML, Doman DB. Fecal Microbiota
Transplantation: A Review of Emerging
Indications Beyond Relapsing Clostridium
di�cile Toxin Colitis.Gastroenterol Hepatol
(N Y). 2015 Jan;11(1):24-32. PMID:
27099570; PMCID: PMC4836576.

61. Hughes HK, Rose D, Ashwood P. The
GutMicrobiota and Dysbiosis in Autism
SpectrumDisorders. Curr Neurol Neurosci
Rep. 2018 Sep 24;18(11):81. doi:
10.1007/s11910-018-0887-6. PMID:
30251184; PMCID: PMC6855251.

62. Durack J, Lynch SV. The gut microbiome:
Relationships with disease and opportunities
for therapy. J ExpMed. 2019 Jan
7;216(1):20-40. doi: 10.1084/jem.20180448.
Epub 2018 Oct 15. PMID: 30322864;
PMCID: PMC6314516.

63. Żebrowska P, Łaczmańska I, Łaczmański
Ł. Future Directions in Reducing
Gastrointestinal Disorders in ChildrenWith
ASDUsing Fecal Microbiota
Transplantation. Front Cell Infect Microbiol.
2021 Feb 26;11:630052. doi:
10.3389/fcimb.2021.630052. PMID:
33718277; PMCID: PMC7952982.

64. Gupta S, Allen-Vercoe E, Petrof EO. Fecal
microbiota transplantation: in perspective.
Therap Adv Gastroenterol. 2016
Mar;9(2):229-39. doi:
10.1177/1756283X15607414. PMID:
26929784; PMCID: PMC4749851.

65. Doenyas C. Novel Personalized Dietary
Treatment for Autism Based on the Gut

Immune-Endocrine-Brain Axis. Front
Endocrinol (Lausanne). 2019 Aug 13;10:508.
doi: 10.3389/fendo.2019.00508. PMID:
31456745; PMCID: PMC6700238.

66. Abdellatif B, McVeigh C, Bendriss G,
Chaari A. The Promising Role of Probiotics
in Managing the Altered Gut in Autism
SpectrumDisorders. Int J Mol Sci. 2020 Jun
10;21(11):4159. doi: 10.3390/ijms21114159.
PMID: 32532137; PMCID: PMC7312735.

Berkeley Pharma Tech Journal of Medicine | 58


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