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Autism Spectrum Disorder (ASD) is a disorder still very poorly understood first recognized in early childhood in the form of a multi-organ system disability caused by impaired neurogenesis and apoptosis, impaired synaptogenesis and synaptic pruning or imbalanced excitatory-inhibition system. Inflammation has been recognised as the pathogenesis of autism but a holistic approach is required. The aetiology is largely unknown and there is no clinical treatment. The gut microbiota may affect symptom manifestation which may benefit from a balanced diet, re-establishment of intestinal permeability, improvement of gut microbiota, raised immunity, supply of antioxidants and detoxification speed. Specific mushrooms may have specific effects on health, well-being, behaviour and fitness and address the potential impact of a dietary mushroom supplement on gastrointestinal inflammation in ASD patients.
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Citation: Bell V, Ferrão J, Chaquisse E, Manuel B and Fernandes T. Role of Mushrooms in Autism. Austin J Nutri
Food Sci. 2019; 7(6): 1128.
Austin J Nutri Food Sci - Volume 7 Issue 6 - 2019
ISSN : 2381-8980 | www.austinpublishinggroup.com
Fernandes et al. © All rights are reserved
Austin Journal of Nutrition and Food
Sciences
Open Access
Abstract
Autism Spectrum Disorder (ASD) is a disorder still very poorly understood
rst recognized in early childhood in the form of a multi organ system disability
caused by impaired neurogenesis and apoptosis, impaired synaptogenesis
and synaptic pruning or imbalanced excitatory-inhibition system. Inammation
has been recognised as the pathogenesis of autism but a holistic approach is
required. The aetiology is largely unknown and there is no clinical treatment.
The gut microbiota may affect symptom manifestation which may benet from
a balanced diet, re-establishment of intestinal permeability, improvement of gut
microbiota, raised immunity, supply of antioxidants and detoxication speed.
Specic mushrooms may have specic effects on health, well-being, behaviour
and tness and address the potential impact of a dietary mushroom supplement
on gastrointestinal inammation in ASD patients.
Keywords: Autism spectrum disorder; Mushrooms; Nutrition; Gut microbiota
Review Article
Role of Mushrooms in Autism
Bell V1, Ferrão J2, Chaquisse E3, Manuel B4 and
Fernandes T5*
1Faculty of Pharmacy, University of Coimbra, Portugal
2Pedagogical University, Mozambique
3National Health Institute, Ministry of Health,
Mozambique
4Faculty of Medicine, Eduardo Mondlane University,
Mozambique
5Faculty of Veterinary Medicine, Lisbon University,
Portugal
*Corresponding author: Fernandes T, Faculty of
Veterinary Medicine, Lisbon University, 1300-477 Lisboa,
Portugal
Received: August 16, 2019; Accepted: September 24,
2019; Published: October 01, 2019
Introduction
Plenty of research has explored the mechanisms behind anxiety,
stress, cognition, memory and depression [1]. Many neural system
diseases are oen neglected and some are hard to understand.
Furthermore, there are very few established explanations or choices
for intervention or managing some of them; especially the most
misconceived ones [2]. Autism spectrum disorder, known since 1938
[3], is a comorbidity (not necessarily implying the presence of multiple
diseases) still very poorly understood, typically rst recognized
in early childhood before the age of 3, and can create challenges
throughout a person’s life. It is still very unclear its aetiology and it is
probably even more uncertain how it could be supported or remedied
in any way. Autism is an example of natural variation also known as
Autism Spectrum Disorder (ASD), aecting some 70 million people
globally (current estimates are that 1 in 100 people are on the autistic
spectrum), dealing with neurological developments in people that
interfere with their ability to communicate and socialize with others
[4]. Genetic, neuro-immune and environmental factors are connoted
[5] despite the fact that each individual case of autism is unique from
others [6]. Autism is not anymore considered a comorbidity neither
one of ve lifelong disorders that were under the umbrella previously
designated Pervasive Developmental Disorders (PDD), a category
of neuro developmental disabilities. But actually, autism spectrum
disorder-ASD means the same thing covering the ve conditions.
Research has shown that autism tends to run in families being a
brain based disorder but not caused by inadequate parenting. With
the exception of neuro-inammatory changes [7], most reported
neurobiological abnormalities in ASD are inconsistent [8]. A usual
misinterpretation around autism is that it is inevitably linked to
intellectual disability [9]. ere are no recognised treatments or
known medication that can directly cure or lessen the symptoms of
autism, some with undesirable side eects or dependency risks. On
the other hand, there have been some a few mainstream approaches
that have been developed and accepted into conventional medicine
that may help with issues associated with or connected to autism [10].
Autism aects all races, ethnic groups, and socioeconomic levels, boys
being more prone than girls. e severity of autism conditions may
be slowed by behavioural therapy for children, helping people deal
with further complications as they grow older [11]. e mainstream
treatment of autism has many side eects. Some studies show that
uncomplicated diet changes, avoiding potential risk factors and
environmental toxins (e.g. heavy metals), incorporating dietary
supplements (e.g. vitamins, probiotics), and some medicinal herbs
and mushrooms may have some signicant benecial eects [12].
However, the heavy metals from some mushrooms indicate that
when consumed high quantity may cause liver or kidney damage and
even death may result [13]. e autism spectrum can benet from a
balanced diet including certain foods and supplements, in particular
those that curtail inammation, re-establish intestinal permeability,
improve the harmony of gut microbiota, raise immunity, supply
antioxidants and speed detoxication [14,15]. Oxidative stress is
common to a myriad of neurological diseases [16]. e production
of Reactive Oxygen Species (ROS) is a common outcome of normal
aerobic cellular metabolism, and determines the cellular redox balance
with antioxidants [17]. ese protect critical biological targets against
[18] therefore, they have been considered as attractive potential
benecial agents to neutralise ROS-mediated neural damage. e
key players in oxidative stress outline evidences of their involvement
in Multiple Sclerosis, Alzheimer’s, Parkinson’s and Huntington’s
diseases [19,20]. Complementary and alternative medical treatments
are commonly used for children with autism spectrum disorders
[21]. However, most treatments have not been adequately studied
and do not have evidence to support their use. is review discusses
the existing evidence supporting the administration of mushroom
products in ASD patients.
Role of Microbiota
Human life spins around a microbial world and human and
animals only exist because they have evolved dealing with
microorganism in environment and food. Human metabolism
represents a conjugation of microbial and human vital roles namely
in health consequences. e microbiome, is a diverse consortium of
bacteria, fungi, protozoa, archaea and viruses that inhabit the gut of
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all mammals, referring to the collection of microbes and their genetic
material, confers a variety of physiologic benets to the host in many
key aspects of life as well as being responsible for some diseases. e
eld is at a stage where more questions than answers are being
generated [22,23]. e gut microbiota has been implicated as a
potential pathway aecting symptom manifestation in cognitive and
neuro developmental disorders, such as anxiety, depression and ASD
[24,25] Incredible advances in our understanding of host-microbe
interactions, with identication of numerous disease-associated
organisms and elucidation of pathogenic mechanisms occurred on
the last two decades [26]. e gut microbiota interact with the human
body via ve communication routes between gut microbiota and
brain [27], including immune, endocrine and neural mechanism
deeply inuencing general growth and development, including
development of the nervous system [28]. Our digestive microbiota is
a partner of homeostasis directly linked to our brains [29] which is
explained by a network of neurons lining our guts that is so extensive
some scientists have nicknamed it our “second brain” [30-32]. At
present there is a lack of consistent ndings relating to the
neurobiology of autism and the inuence of environment including
nutrition [33]. Hormones, some heavy metals and endocrine
disrupting compounds (mostly man-made, found in various materials
such as pesticides, additives or contaminants in food, and personal
care products), have undesired harmful eects on the embryonic and
foetal neuro development and in the evolution of ASD [34,35]. e
sources of the microorganisms that make up the gut ecosystem, how
and why it varies from one person to another, and how the
composition of this microbial community inuences human
digestion, physiology, metabolism, development, and diseases are still
poorly understood [36,37]. ere is a strong link between ASD and
dysbiosis, including high degree of mental distress between these
ostensibly contrasting diagnoses [38,39]. Although microbiota is
known to alter host immune function including inammatory
cytokine production, the relationship between abnormal microbiota
and cytokine production in ASD has been scarce [40,41]. Development
of ASD, including autism, is based on a combination of genetic
predisposition and environmental factors ASD being among the most
heritable of all neuropsychiatric disorders [42,43]. Recent data partly
explains the diverse neuro immunological abnormalities in ASD and
propose a diverse and complex multifactorial aetiology including a
pathogenetic role of intestinal microbiota in autism [44-46].
Abundant research suggests a connection between gut microbiome
and autism-like behaviours. Long-term benet eects of faecal
transplant or Microbiota Transfer erapy (MTT) on autism
symptoms and gut health, which persisted long aer treatment, was
demonstrated on children diagnosed with ASD [47]. e human gut
microbiota, through interactions between the microbiome and ASD,
may impact on the connection between feeding, nutrition and
metabolism with ASD [48,49]. e microbiome being an interface
between environmental and genetic risk factors associated with ASD
reect that changes in the microbiome may contribute to symptoms
of neuro developmental disease [50,51]. Gastrointestinal
comorbidities, including acute and chronic constipation and
diarrhoea, occur in children with ASD associated with the harshness
of the neuro behavioural disorder [48]. Gut microbial imbalance may
correspond with behavioural abnormality in ASD patients. Since the
impact of diet on the microbiota composition in children with ASD is
still broadly unexplained [52]. Understanding of the relationship
among diet, gut ora and host on mitochondrial dysfunction and
oxidative stress in the cells, could open up new lines of research on
ASD, including potential novel treatment strategies [53-56].
Impairment of physiological regulatory mechanisms governing
metabolism, immune response, organ function or unbalance of the
gut microbiota are quite complex and critical in gastrointestinal
functions and disturbances. e integrity of the gastrointestinal
mucosal barrier and the symbiotic relationship with commensal
bacteria play a vital role in the gut pathogenesis and is involved in
regulating normal functions including motility, permeability, and
mucosal immune function [57-59] (Figure 1). Derangements in the
gut microbiota in children with ASD have been reported [60] and
liaisons between specic microbial genera and some symptoms of
ASD have been described [61,62]. e gut microbiota of children with
ASD is less diverse, varies between individuals, and exhibits lower
levels of Bidobacterium and Firmicutes and higher levels of
Lactobacillus, Clostridium, Bacteroidetes, and Desulfovibrio [63]. It is
noticeable that the human body lacks endogenous enzymes to
degrade many plant polysaccharides, such as cellulose, hemicellulose
(e.g. xylan), complex pectins, and arabinose. In contrast, the human
colonic microbiota yields more than 80 dierent glycosyl hydrolase
families [64,65]. In this way, the gut microbiota may have evolved as
an adaptation to allow extraction of maximal energy (e.g. short chain
fatty acids, acetate, propionate, butyrate and other elements (e.g.
serotonin, bile acids, bioactive lipids) from food sources [66] and
actually it is widely known that the human body is composed of 10
times more microbial cells than body cells [67]. e plausibility of
manipulative procedures to change microbiome evolution establishes
the forecast of a spectrum of novel therapeutic paths such as
microbiome-mediated therapies, probiotic, antibiotic or dietary
administrations that may represent hope to patients and families
living with ASD [68]. Gut bacteria are not only critical for regulating
gut metabolism, but also important for host immune system [69,70].
e short-chain volatile fatty acids, are produced in the distal colon
by microbial fermentation of carbohydrates and endogenous
substrates, such as mucus, epithelial cells, and digestive enzymes [71].
is is of great advantage to the host humans since most of the
enzymes needed to degrade the polymeric carbohydrate molecules
(e.g. cellulose and chitin) present in cell wall of plants are not
produced endogenously [72,73]. Still unclear, but most likely, there
are eective links between dietary, metabolic, infective-related events,
gastrointestinal factors and the behavioural aggravations and
Figure 1: The concept of the overlap syndrome of GI disorders and ASD [57].
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exemptions of ASD [7,74]. ere is accumulated evidence of an
association between specic individual harmful bacteria and
symptoms of ASD which is oen associated with medical
comorbidities and gastrointestinal dysfunction [75]. For example,
some nutrient deciencies, microbiota luxuriance, decreased
Bacteroidetes-to-Firmicutes ratio and abundance of Desulfovibrio
were related to ASD symptoms [76-78]. However, few studies have
assessed dietary intake, namely recommended daily intake of bre,
and microbiota in ASD children [79]. Gut-derived factors, such as
dietary or enteric bacterially produced VFA, may therefore be
plausible environmental agents that can trigger ASDs. As a critical
modulator of enteric and central nervous systems development and
function, amygdala dysregulation [80] and serotonin may be the
nexus for the microbiota-gut-brain axis in ASD since one of the most
prominently established ndings in autism is the elevation of
serotonin in the brain [81,82]. e idea that systemic bacterial
infections play a role in the genesis of symptoms of autism is gaining
ground associated with inammation of the intestinal mucosa leading
to the introduction of bacterial components, including neurotoxins,
into the bloodstream, creating oxidative stress causing immune
dysfunction. e tridirectional interactions between the central
nervous system, microbiota and the gastrointestinal tract (microbiota-
brain-gut axis) may mediate therapies and be a safe and eective
treatment for ASD [83-85].
Role of Mushrooms
Mushrooms are rich in bioactive metabolites, including
polysaccharides, enzymes (e.g. superoxide dismutase, ribonucleases,
laccases), proteins (ribosome inactivating proteins), dietary bres
(β-Glucans), and many other biomolecules (secondary metabolites,
lectins, antifungal proteins, ubiquitin-like proteins, protease
inhibitors), which have been shown to be successful in the prevention
and treatment of several human health hazards [86-88] Macro-
fungi are both food and a signicant nutritional supplement for
humans. However, several fungus species accumulate both important
nutritional elements and heavy metals in their fruit bodies [89].
Although living organisms need certain elements such as iron,
cobalt, copper, manganese, chrome and zinc in trace amounts,
excessive amounts of these elements may create toxic eects on
these living organisms [90]. Many people on the spectrum take
multiple medications, which can lead to serious side eects and may
not even be eective. Families of children with autism and related
disorders, due to anxiety, may turn to therapies that are not based
in the realm of conventional medical or psychological practice, but
this matter is quite complex and ndings should not be generalized
[91]. e most eective treatment is a combination of specialized
and supportive educational programming, communication training,
social skills support and behavioural intervention [92]. Treatments
do not address the core symptoms of the disorder and there are no
medications that cure ASD, but it can help provide some control
over aggression, mood problems, rigid behaviour, and attention
decits. Associated problems such as seizures, disrupted sleep
patterns, gastrointestinal problems or dietary imbalances should
have medical care and oen use complementary and alternative
medicine [93,94]. e use of more than one antipsychotic medication
in the treatment of child and adolescent psychiatric conditions has
increased over the last decade which is concerning, considering
the risks of adverse eects associated with these medications [95].
Complementary and Alternative Medical (CAM) treatments are
commonly used for children with ASD including mind and body
practices, energy medicine, biomedical treatments and natural
products [96]. ASD being multifactorial demands collaborative
intervention of health professionals. Gluten- and casein-free diet in
children showed little evidence of benecial eects for the symptoms
of ASD [97]. Mushroom nutrition may come into play in the
association between dietary factors and microbiota composition as
mushrooms we have shown to increase Lipoxin A4 and having a
high content in superoxide dismutase that can cross the blood brain
barrier [98]. e most commonly used mushrooms as potent health-
boosters include Chaga (Inonotus obliquus), Reishi (Ganoderma
lucidum), Turkey Tail (Trametes versicolor, Coriolus versicolor),
Shiitake (Lentinula edodes), Lion’s Mane (Hericium erinaceus), and
Cordyceps (Cordyceps sinensis). e connection between mushroom
nutrition and immune system is well recognised [99], however the
true integration of research between mushroom nutrition, animal
energy status and immune function is still far from clear. ere
are multiple recognised clinical and immune modulating uses of
mushrooms due to their content in β-glucans [30,100]. Mushrooms
contain immunostimulants (β-glucans, lipopolysaccharide, and
polyinosinic: polycytidylic acid) that can strengthen and increase
immune system activity. Some contain immunomodulators that
can adjust the level of function in the individual’s immune system
[101] and their eects on various cancers have been well documented
[102] while the folate in mushrooms plays an important role in DNA
synthesis and repair [103]. If a person is fungiphobic, mushrooms
are not a path of nutritional recovery for ASD. For people with ASD
specic mushrooms (Reishi, Maitake, Shiitake, and Cordyceps) may
have specic eects on health, well-being, behaviour and tness.
Cordyceps, a combination from a caterpillar and a fungus, is not a
mushroom but a parasitic fungus infecting insects at dierent phases
of their evolution and it is being cultivated for its outstanding health
benets. Cordycepin, rich in some 20 nucleosides and their related
compounds, aects the synergistic actions of immune cells and
increases the cytokine network contributing to the increase of cell
receptors and control of cellular and humoral acquired immunity
[104,105]. For children with ASD who enjoy eating common
mushrooms (white button, shiitake, and oyster), there is a matter
of chance for repairing functional activities. People on the autism
spectrum can over-respond too many challenges such as toxins and
allergens, and under-react to a seemingly harmless foreign substance
such as viruses, yeast, and intracellular bacteria. ese responses
require a specic type of immune system response, which can be
Figure 2: Fruiting body and mycelium of Pleurotus giganteous (left) and
Hericium erinaceus (right).
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eective using mushrooms to successfully induct the 2 cells which
secrete cytokines [106,107].
Autism, Neuroimmunity and Environmental
Factors
Autism is a severe neurological condition and one of the most
mysterious and challenging lifelong developmental disability of
present medicine. Contrary to popular opinion, autism is not just
the congenital condition once assumed to be and results from the
combination of genetic and environmental factors being preventable,
and even treatable, once understood the underlying causes [108,109].
Parental age, perinatal risks, medication, smoking and alcohol abuse,
nutrition deciencies, some vaccinations, teratogenic compounds,
toxic exposures, and even extreme psychosocial factors may
constitute risk factors for adverse outcomes. Several other factors may
reduce the risk of a child to develop ASD such an adequate vitamin
D during pregnancy and lactation, avoidance of environmental
toxins (e.g. heavy metals, pesticides, alcohol) [110]. Several herbal
medicine products were found positive on ADHD (attention decit-
hyperactivity disorder) cases and the most promised were mushrooms
and a plant named Bacopa monnieri which may be a helpful natural
remedy for autism [111,112]. e culinary medicinal fungus lion’s
mane Hericium erinaceus (Figure 2) showed some scientic reason
to believe that could be of some marginal help on these. Other
studies have documented that this mushroom and oyster mushroom
(Pleurotus giganteous) could be of benet to symptoms relating to
anxiety and depression, which may relate to both autism and ADHD.
Daily consumption of these mushrooms may keep people away
from several life-threatening disorders. However still needs further
scientic validation to consider these mushrooms as useful in the
prevention or treatment of dementia and cognitive dysfunction
[113,114]. Cordyceps (Cordyceps militaris) (Figure 3) is considered
to be neuroprotective to the highest degree. No direct research has
been undertaken to manifest a solid link between cordyceps and
ADHD or autism, though the makings of a link are already clear
[115,116]. Globally, more than 300 million people of all ages suer
from depression, resulting from a complex interaction of social,
psychological and biological factors. erefore, there is an interest in
nding a safer compound with robust and rapid antidepressant eect
namely on mild cases and for children and adolescents. Cordyceps
promotes strong anti-depressant potential [117], which could be an
ally to those with autism and which may benet ADHD [118,119].
Reishi (Ganoderma lucidum) mushroom could also be supportive
to both ADHD and autism. Some studies suggest it could have anti-
depressant-like eects and neuroprotective activity [120] but extracts
of G. lucidum should be used with caution as there appears to be
potential for toxicity [121]. erefore, researchers suggest that reishi
should be administered in combination with traditional treatment
rather than replacing it [122]. Psilocybin, the psychoactive compound
in magic mushrooms, is proving a prodigious treatment for anxiety,
depression, addiction, and one study even found it might lead to
neurogenesis, or the regrowth of brain cells, acting as serotonin
agonists [123]. But there are only few small studies indicating
that psilocybin could produce great results and pharmaceutical
companies are not interested in researching an inexpensive substance
[124]. Safety is clearly one issue that is important to discuss when
contemplating the use of psychedelic drugs as medical or therapeutic
treatments [125,126].
Children and Ecosystems
e interaction between three sources of information, genetic,
past experience and present environment, from conception onwards,
governs the physical and emotional state of humans, the homeostasis
of the natural human systems [127]. Decient nutrition and an
imbalanced inner ecosystem is most plausible connected to autism.
For example, zinc plays a role on neuronal depolarization at synapses
and its deciency or disrupted zinc dynamics might be linked to
individuals with ASDs [128]. Enabling an ecient child’s immune
system and ability to metabolise nutrients and remain free of toxins,
is a condition from birth. Subsequently, aer a typical programme
of vaccination, the child’s levels of mercury and aluminium from
vaccine adjuvants crosses increase and may cause the child’s brain
and nervous systems not to function as they should [129]. Two
subtypes of ASD, with or without gastrointestinal disorders, have been
identied, possibly reecting dierent grades of inammation and
mucus production, which has impact on the implementation of diet
or dietary supplements dierent for the subtypes [130]. To balance
the inner ecosystem may improve autism showing that diet is indeed
key to treat autism and its milder forms in the subtype with bowel
dysfunctions, and this balance may be achieved by adding probiotics-
rich diets (fermented foods and beverages) or prebiotics (mushroom
bres). ese fermented foods and mushrooms build strong, healthy
immune and digestive systems. Soon aer incorporating some
of these into their diets, autistic children show improvements on
digesting high-quality lipids rich in raw, unsaturated fatty acids
essential to healing [131]. Epidemiological evidence shows also a clear
association between gut problems and skin disorders [132] although
autism’s co-morbidity with hypomelanosis is justied by genetic
and epigenetic variants that protect against vitamin-D deciency.
Children with reduction or absence of the pigment melanin have
increased autism risk because parents tend to reduce sun exposure
being aware of photosensitivity and skin-cancer [133]. Most research
comprises epidemiological studies detailing age of parents, use of
antidepressants, mothers with diabetes and other situations which
do not demonstrate cause and eect and originate conicting
conclusions. Some studies suggest that taking vitamin D and vitamin
B9 (folate), supplements during pregnancy can decrease the baby’s
autism risk. But the evidence is not denitive [134]. Folate and folic
acid are dierent since folic acid is a synthetic form of vitamin B9 and
the majority of folic acid is not converted to the active form of vitamin.
e un-metabolized folic acid may build up and be associated with
Figure 3: Image of Cordyceps sinensis (a genus of Ascomycete fungi).
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several health problems. It is dicult to link autism to environmental
ecosystem and besides pollutants and chemicals anything altering the
likelihood of having a condition and not encoded in an individual’s
DNA is a risk factor. Folate has a crucial role in cell growth and the
formation of DNA. Periconceptional folic acid intake may reduce
ASD risk in those with high prenatal air pollution exposure [135].
Vitamin-D enhancement may aid treatment and prevention of
autism in children however; intervention must start long before on
nutritional status of mothers before and during pregnancy, thereby
allowing changes to be performed. e mechanisms of how these
processes occur are not fully understood [136,137].
Concluding Remarks
Nature functions in an innitely more complex manner than
we can understand using our simplied models of reality. e
impact of dietary intake on the gut microbiota composition was not
systematically investigated although alterations in its prole have
been conrmed in children with ASD [138-140]. Each person with
ASD is unique, and intervention plans must be individualized based
on the needs of the individual and family. Recommended services
should be based on proven interventions with a strong evidence
base emphasizing a holistic approach to health maintenance. Dietary
therapy is insucient to eectively treat autism, but it can be used as
a complement to medical and psychological interventions. e use of
some mushrooms may reduce the severity of issues springing from
autism or ADHD, however, being a delicate collection or network
of causes, lifestyle is very important and mushrooms may have only
peripheral benet. Some treatments have been unsuccessful, some
have undesirable side eects, and others require more research.
Conict of Interest
e authors declare that the work was conducted in the absence
of any commercial or nancial relationships that could be construed
as a potential conict of interest. No research involving humans or
animals, therefore informed consent not necessary and all ethical
issues were taken into consideration.
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... Mushrooms-based dietary biotech products with different formulation have also been demonstrated to be neuroprotective (Barros et al. 2008;Palacios et al. 2011;P h a ne ta l . , 2014a, b, 2015, 2017Cornelius et al. 2013;Wang et al. 2014;Bandara et al. 2015;Friedman 2015;Zhang et al. 2016aZhang et al. , b, 2017Brandalise et al. 2017;Solayman et al. 2017;Lemieszek et al. 2018;Rossi et al. 2018;Yin et al. 2018;Bell et al. 2019;Dhakal et al. 2019;Jang et al. 2019;Ho et al. 2020;Lucius 2020). ...
... For many years, natural products derived from medicinal plants, fruits, and vegetables have been regarded as primary resources for the discovery of potential therapeutic agents. They have been effective as anti-PD agents due to their neuroprotective properties, antioxidative and anti-inflammatory activities, as well as inhibitory effects regarding iron accumulation, protein misfolding, maintenance of proteasomal degradation, and mitochondrial homeostasis (Solayman et al. 2017;Rossi et al. 2018;Yin et al. 2018;Bell et al. 2019;Dhakal et al. 2019;Jang et al. 2019;Ho et al. 2020). ...
... Autistic patients may benefit from a balanced diet rich with antioxidants, improvement of gut microbiota, and immunity. Mushroom-derived dietary supplementation may decrease gastrointestinal inflammation and improve health conditions in patients (Bell et al. 2019). ...
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Diversity of wild and cultivated macrofungi as edible and medicinal mushrooms has long been known by humans as a source of valuable food and medicines used by tradipraticians. In the fungal kingdom, macrofungi taxonomically belong to two phyla, the Basidiomycota (class Agaricomycetes) and Ascomycota (class Pezizomycetes). Macrofungi have been used in traditional Asian and European Medicines, and based on 90,000 known worldwide distributed mushroom species, are considered an important resource for modern clinical and pharmacological research. They are regarded as a source of high- and low-molecular-weight bioactive compounds (alkaloids, lipids, phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) with more than 130 therapeutic effects (anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, etc.). There is also scientific evidence of using macrofungi as neuroprotectants, that is, Agaricus blazei (= Agaricus subrufescens), Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Pleurotus ostreatus, and Trametes versicolor. However, their neuroprotective effects have not been fully explored. This review discusses recent advances in research on the neuroprotective potential of macrofungi and perspectives for their application as neuroprotectants in biomedicine to prevent, support, or cure neurodegenerative disorders.
... Mushrooms-based dietary biotech products with different formulation have also been demonstrated to be neuroprotective (Barros et al. 2008;Palacios et al. 2011;P h a ne ta l . , 2014a, b, 2015, 2017Cornelius et al. 2013;Wang et al. 2014;Bandara et al. 2015;Friedman 2015;Zhang et al. 2016aZhang et al. , b, 2017Brandalise et al. 2017;Solayman et al. 2017;Lemieszek et al. 2018;Rossi et al. 2018;Yin et al. 2018;Bell et al. 2019;Dhakal et al. 2019;Jang et al. 2019;Ho et al. 2020;Lucius 2020). ...
... For many years, natural products derived from medicinal plants, fruits, and vegetables have been regarded as primary resources for the discovery of potential therapeutic agents. They have been effective as anti-PD agents due to their neuroprotective properties, antioxidative and anti-inflammatory activities, as well as inhibitory effects regarding iron accumulation, protein misfolding, maintenance of proteasomal degradation, and mitochondrial homeostasis (Solayman et al. 2017;Rossi et al. 2018;Yin et al. 2018;Bell et al. 2019;Dhakal et al. 2019;Jang et al. 2019;Ho et al. 2020). ...
... Autistic patients may benefit from a balanced diet rich with antioxidants, improvement of gut microbiota, and immunity. Mushroom-derived dietary supplementation may decrease gastrointestinal inflammation and improve health conditions in patients (Bell et al. 2019). ...
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Badalyan S.M. et Rapior S. The neurotrophic and neuroprotective potential of macrofungi. In: Medicinal Herbs and Fungi – Neurotoxicity vs. Neuroprotection. Agrawal D.C. et Dhanasekaran M. (Eds). Publisher Springer. Chapter 2: 37-78 (2021). doi:10.1007/978-981-33-4141-8_2 ____ Diversity of wild and cultivated macrofungi as edible and medicinal mushrooms has long been known by humans as a source of valuable food and medicines used by tradipraticians. In the fungal kingdom, macrofungi taxonomically belong to two phyla, the Basidiomycota (class Agaricomycetes) and Ascomycota (class Pezizomycetes). Macrofungi have been used in traditional Asian and European Medicines, and based on 90,000 known worldwide distributed mushroom species, are considered an important resource for modern clinical and pharmacological research. They are regarded as a source of high- and low-molecular-weight bioactive compounds (alkaloids, lipids, phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) with more than 130 therapeutic effects (anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, etc.). There is also scientific evidence of using macrofungi as neuroprotectants, that is, Agaricus blazei (= Agaricus subrufescens), Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Pleurotus ostreatus, and Trametes versicolor. However, their neuroprotective effects have not been fully explored. This review discusses recent advances in research on the neuroprotective potential of macrofungi and perspectives for their application as neuroprotectants in biomedicine to prevent, support, or cure neurodegenerative disorders. Corresponding authors: s.badalyan@ysu.am, sylvie.rapior@umontpellier.fr
... The first FDA-approved psychedelic treatment, controlled substance esketamine, from hallucinogenic mushrooms is considered a major "breakthrough for depression." Edible mushrooms (e.g., Chaga-Inonotus obliquus, Reishi-Ganoderma lucidum, Turkey Tail-Coriolus versicolor, and Shiitake-Lentinula edodes) are rich in ketamine and ergothioneine and have been successfully used on mental health highlighting the potential clinical and public health importance of mushroom consumption as a means of reducing depression and preventing other diseases (180,181). ...
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The potential of edible mushrooms as an unexploited treasure trove, although rarely included in known food guidelines, is highlighted. Their role in shielding people against the side effects of an unhealthy stylish diet is reviewed. Mushrooms complement the human diet with various bioactive molecules not identified or deficient in foodstuffs of plant and animal sources, being considered a functional food for the prevention of several human diseases. Mushrooms have been widely used as medicinal products for more than 2,000 years, but globally the potential field of use of wild mushrooms has been untapped. There is a broad range of edible mushrooms which remain poorly identified or even unreported which is a valuable pool as sources of bioactive compounds for biopharma utilization and new dietary supplements. Some unique elements of mushrooms and their role in preventative healthcare are emphasized, through their positive impact on the immune system. The potential of mushrooms as antiviral, anti-inflammatory, anti-neoplastic, and other health concerns is discussed. Mushrooms incorporate top sources of non-digestible oligosaccharides, and ergothioneine, which humans are unable to synthesize, the later a unique antioxidant, cytoprotective, and anti-inflammatory element, with therapeutic potential, approved by world food agencies. The prebiotic activity of mushrooms beneficially affects gut homeostasis performance and the balance of gut microbiota is enhanced. Several recent studies on neurological impact and contribution to the growth of nerve and brain cells are mentioned. Indeed, mushrooms as functional foods' nutraceuticals are presently regarded as next-generation foods, supporting health and wellness, and are promising prophylactic or therapeutic agents.
... The most commonly used mushrooms as potent health-boosters, which may bring some hope to autistic children and families, include Chaga (Inonotus obliquus), Reishi (Ganoderma lucidum), Turkey Tail (Coriolus versicolor), Shiitake (Lentinula edodes), Lion's Mane (Hericium erinaceus), Cordyceps (Cordyceps militaris), and oyster mushroom (Pleurotus giganteous). They have shown beneficial to symptoms relating to anxiety and depression, which are related to both autism and attention deficit-hyperactivity disorder (ADHD) [211]. ...
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The defining characteristics of the traditional Sub-Saharan Africa (SSA) cuisine have been the richness in indigenous foods and ingredients, herbs and spices, fermented foods and beverages, and healthy and whole ingredients used. It is crucial to safeguard the recognized benefits of mainstream traditional foods and ingredients, which gradually eroded in the last decades. Notwithstanding poverty, chronic hunger, malnutrition, and undernourishment in the region, traditional eating habits have been related to positive health outcomes and sustainability. The research prevailed dealing with food availability and access rather than the health, nutrition, and diet quality dimensions of food security based on what people consume per country and on the missing data related to nutrient composition of indigenous foods. As countries become more economically developed, they shift to “modern” occidental foods rich in saturated fats, salt, sugar, fizzy beverages, and sweeteners. As a result, there are increased incidences of previously unreported ailments due to an unbalanced diet. Protein-rich foods in dietary guidelines enhance only those of animal or plant sources, while rich protein sources such as mushrooms have been absent in these charts, even in developed countries. This article considers the valorization of traditional African foodstuffs and ingredients, enhancing the importance of establishing food-based dietary guidelines per country. The crux of this review highlights the potential of mushrooms, namely some underutilized in the SSA, which is the continent’s little exploited gold mine as one of the greatest untapped resources for feeding and providing income for Africa’s growing population, which could play a role in shielding Sub-Saharan Africans against the side effects of an unhealthy stylish diet.
... Autism Spectrum Disorder (ASD) is a disorder still very poorly understood, caused by genetic or environmental factors, first recognized in early childhood in the form of a multi organ system disability caused by impaired neurogenesis and apoptosis, impaired synaptogenesis and synaptic pruning or imbalanced excitatory-inhibition system [240]. [243]. ...
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In Sub-Saharan Africa, despite poverty, chronic hunger and food insecurity, traditional eating has been related to positive health outcomes and sustainability. There is little health research on diet quality based on what African people consume. The defining characteristics of the traditional African cuisine are the richness in herbs and spices, fermented foods and beverages, and healthy and whole ingredients used. However, as countries in this region become more economically developed, there is a shift to “modern” occidental foods rich in saturated fats, sugar and sweeteners. As a result, there are increased incidences of previously unreported ailments due to unbalanced diet. The regular practice of infinite international aid to the region to curb food insecurity has been unsustainable, ineffective and with no end in sight. Local increase in production and productivity is imperative. Protein rich foods in dietary guidelines enhance only those of animal or plant sources while rich protein sources such of mushroom, has been absent in these charts. This article considers the valorisation of traditional African foods and the importance of establishing an African Food-Based Dietary Guidelines (AFBDGs), an unprecedented Food Pyramid, along with the added emphasis on the potential of African mushrooms, which may play a role in shielding Sub-Saharan Africans against the side-effects of a western stylish diet and promote health. It enhances the preventive role of mushrooms in viral diseases and other disorders.
... According to Table 1, the species of HE and GL are most often mentioned to contain bioactive components with a role in normalizing HD effects. Oxidative stress, the common cause of neurodegenerative dysfunction, is controlled by complementary methods that include medicinal plants and mushrooms [123]. In this sense, the microbiota is a key element that modulates the anti-inflammatory response through (control) cytokines' production. ...
Article
Neurodegenerative diseases (NDs) represent a common neurological pathology that determines a progressive deterioration of the brain or the nervous system. For treating NDs, comprehensive and alternative medicines have attracted scientific researchers' attention recently. Edible mushrooms are essential for preventing several age-based neuronal dysfunctions such as Parkinson's and Alzheimer's diseases. Mushroom such as Grifola frondosa, Lignosus rhinocerotis, Hericium erinaceus, may improve cognitive functions. It has also been reported that edible mushrooms (basidiocarps/mycelia extracts or isolated bioactive compounds) may reduce beta-amyloid-induced neurotoxicity. Medicinal mushrooms are being used for novel and natural compounds that help modulate immune responses and possess anti-cancer, anti-microbial, and anti-oxidant properties. Compounds such as polyphenols, terpenoids, alkaloids, sesquiterpenes, polysaccharides, and metal chelating agents are validated in different ND treatments. This review aims to assess mushrooms' role and their biomolecules utilization for treating different kinds of NDs. The action mechanisms, presented here, including reducing oxidative stress, neuroinflammation, and modulation of acetylcholinesterase activity, protecting neurons or stimulation, and regulating neurotrophins synthesis. We also provide background about neurodegenerative diseases and in-silico techniques of the drug research. High costs associated with experiments and current ethical law imply efficient alternatives with limited cost value. In silico approaches provide an alternative method with low cost that has been successfully implemented to cure ND disorders in recent days. We also describe the applications of computational procedures such as molecular docking, virtual high-throughput screening, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design. They were reported against various targets in NDs.
... Agaricomycetes mushrooms (phylum Basidiomycota) are rich sources of bioactive compounds (alkaloids, phenolics, polyketides, polysaccharides, proteins, ribosomal and non-ribosomal peptides, steroids, terpenoids, etc.) possessing more than 130 therapeutic effects (analgesic, antibacterial, antifungal, anti-inflammatory, antioxidant, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, mitogenic/regenerative, etc.) [1][2][3][4][5][6][7]. They have also been reported as neuroprotective and anti-depressive agents [8][9][10][11][12][13][14]. New screening strategies based on innovative genetic approaches have identified novel mushroom metabolites-derived products widely applicable in biomedicine [15]. ...
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Badalyan S.M. et Rapior S. Agaricomycetes medicinal mushrooms with potential potential neuroprotective activity growing in rmenia. Proceedings of the Yerevan State University, Chemistry and Biology, 54 (3), 196-203 (2020). hal-03090953 _____ The Agaricomycetes mushrooms (phylum Basidiomycota) are recognised sources of valuable food and medicines. They are producers of bioactive compounds (phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) possessing around 130 therapeutic effects (antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, etc.). Mushrooms are also reported as potential neurotrophic and neuroprotective agents. Seventeen edible and inedible agaricomycetous species from different taxonomic and ecological groups have been reported in Armenia to possess neuroprotective activity. Evaluation resource value and biotechnological potential of Armenian agaricomycetous mushrooms will assist further development of novel myco-pharmaceuticals to prevent and mitigate different disorders, including neurodegenerative.
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New research points to a possible link between autism spectrum disorder (ASD) and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites, or leaky gut in autistic people are described. Various altered metabolite levels were observed in the blood and urine of autistic children, many of which were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides (LPS). A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients, triggering new body responses or an altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in cells, altered tight junctions in the blood-brain barrier and structural changes in the cortex, hippocampus, amygdala and cerebellum were also detected. Moreover, this paper suggests that ASD is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between ASD and gut microbiota is not yet well established, the consumption of specific probiotics may represent a side-effect free tool to re-establish gut homeostasis and promote gut health. The diagnostic and therapeutic value of bacterial-derived compounds as new possible biomarkers, associated with perturbation in the phenylalanine metabolism, as well as potential therapeutic strategies will be discussed.
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There are two main paradigms for brain-related science, with different implications for brain-focused intervention or advancement. The paradigm of homeostasis (“stability through constancy,” Walter Cannon), originating from laboratory-based experimental physiology pioneered by Claude Bernard, shows that living systems tend to maintain system functionality in the direction of constancy (or similitude). The aim of physiology is to elucidate the factors that maintain homeostasis, and therapeutics aim to correct abnormal factor functions. The homeostasis paradigm does not formally recognize influences outside its controlled experimental frames and it is variable in its modeling of neural contributions. The paradigm of allostatic orchestration (PAO) extends the principle of allostasis (“stability through change”) as originally put forth by Peter Sterling. The PAO originates from an evolutionary perspective and recognizes that biological set points change in anticipation of changing environments. The brain is the organ of central command, orchestrating cross-system operations to support optimal behavior at the level of the whole organism. Alternative views of blood pressure regulation and posttraumatic stress disorder (PTSD) illustrate differences between the paradigms. For the PAO, complexities of top-down neural effects and environmental context are foundational (not to be “factored out”), and anticipatory regulation is the principle of their interface. The allostatic state represents the integrated totality of brain-body interactions. Health itself is an allostatic state of optimal anticipatory oscillation, hypothesized to relate to the state of criticality, a mathematical point of poise between phases, on the border between order and disorder (or the “edge of chaos”). Diseases are allostatic states of impaired anticipatory oscillations, demonstrated as rigidifications of set points across the brain and body (disease comorbidity). Conciliation of the paradigms is possible, with “reactive homeostasis” resolved as an illusion stemming from the anticipation of environmental monotony. Considerations are presented with respect to implications of the two paradigms for brain-focused intervention or advancement; the hypothesis that the state of criticality is a vehicle for evolutionary processes; concordance with a philosophy of freedom based on ethical individualism as well as self-creativity, non-obsolescence, empowerment, and citizenship; and concluding reflections on the science and ethics of the placebo, and the potential for virtuous cycles of brain-Anthropocene interactions.
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A complex bidirectional communication system exists between the gastrointestinal tract and the brain. Initially termed the "gut-brain axis" it is now renamed the "microbiota-gut-brain axis" considering the pivotal role of gut microbiota in maintaining local and systemic homeostasis. Different cellular and molecular pathways act along this axis and strong attention is paid to neuroactive molecules (neurotransmitters, i.e., noradrenaline, dopamine, serotonin, gamma aminobutyric acid and glutamate and metabolites, i.e., tryptophan metabolites), sustaining a possible interkingdom communication system between eukaryota and prokaryota. This review provides a description of the most up-to-date evidence on glutamate as a neurotransmitter/neuromodulator in this bidirectional communication axis. Modulation of glutamatergic receptor activity along the microbiota-gut-brain axis may influence gut (i.e., taste, visceral sensitivity and motility) and brain functions (stress response, mood and behavior) and alterations of glutamatergic transmission may participate to the pathogenesis of local and brain disorders. In this latter context, we will focus on two major gut disorders, such as irritable bowel syndrome and inflammatory bowel disease, both characterized by psychiatric co-morbidity. Research in this area opens the possibility to target glutamatergic neurotransmission, either pharmacologically or by the use of probiotics producing neuroactive molecules, as a therapeutic approach for the treatment of gastrointestinal and related psychiatric disorders.
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Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.
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Hippocrates statement that "All disease begins in the gut" continues to be up to date more than 2000 years later. Growing number of scientific reports focus on the important role of intestinal microorganisms for modulation of many systems and human behavior. As a key component of the gut brain, gut microbiota influences the development and maturation of the hypothalamic-pituitary-adrenal axis, affects the development and function of the immune system, regulates the blood-brain barrier, modulates the synthesis and recognition of neurotransmitters, regulates neurogenesis, formation of myelination and supports the development and function of the brain. Disruption of gut-brain axis function is associated with alterations in the stress response and might contribute to neuropsychiatric diseases as depression, autistic spectrum disorders, rapid eye movement sleep behavior disorder, Parkinson disease, Alzheimer disease and other mental conditions. Studies in animal models are crucial for guiding research on brain-gut-microbiome axis in humans, as the impact of microbiota on specific brain regions and aspects of animal behavior will help in the selection of tasks for cognitive assessment. Exploring the interaction of gut microbes and human brain will not only allow us to better understand the pathogenesis of neuropsychiatric disorders, but will also provide us new opportunities for the design of novel immuno-or microbe-based therapies.
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The gut microbiota is extremely important for the health of the host across its lifespan.Recent studies have elucidated connections between the gut microbiota and neurological diseaseand disorders such as depression, anxiety, Alzheimer’s disease (AD), autism, and a host of otherbrain illnesses. Dysbiosis of the normal gut flora can have negative consequences for humans,especially throughout key periods during our lifespan as the gut microbes change with age in bothphenotype and number of bacterial species. Neurologic diseases, mental disorders, and euthymicstates are influenced by alterations in the metabolites produced by gut microbial milieu. Weintroduce a new concept, namely, the mycobiota and microbiota-gut-brain neuroendocrine axis anddiscuss co-metabolism with emphasis on means to influence or correct disruptions to normal gutflora throughout the lifespan from early development to old age. These changes involveinflammation and involve the permeability of barriers, such as the intestine blood barrier, the blood–brain barrier, and others. The mycobiota and microbiota–gut–brain axis offer new research horizonsand represents a great potential target for new therapeutics, including approaches based aroundinflammatory disruptive process, genetically engineered drug delivery systems, diseased cellculling “kill switches”, phage-like therapies, medicinal chemistry, or microbial parabiosis to namea few.
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The link between gut microbes and autism spectrum disorders (ASD) has been already observed in some studies, but some bacterial families/species were found to be inconsistently up or down regulated. This issue has been rarely explored in the Chinese population. In this study, we assessed whether or not gut microbiota dysbiosis was associated with children with ASD in China. We enrolled 45 children with ASD (6–9 years of age; 39 boys and 6 girls) and 45 sex- and age-matched neurotypical children. Dietary and other socio-demographic information was obtained via questionnaires. We characterized the composition of the fecal microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The ASD group showed less diversity and richness of gut microbiota than the neurotypical group, as estimated by the abundance-based coverage estimator index and the phylogenetic diversity index. The analysis of beta diversity showed an altered microbial community structure in the ASD group. After adjustment for confounders and multiple testing corrections, no significant group difference was found in the relative abundance of microbiota on the level of the phylum. At the family level, children with ASD had a lower relative abundance of Acidaminococcaceae than the healthy controls. Moreover, a decrease in the relative abundance of genera Lachnoclostridium, Tyzzerella subgroup 4, Flavonifractor, and unidentified Lachnospiraceae was observed in ASD group. This study provides further evidence of intestinal microbial dysbiosis in ASD and sheds light on the characteristics of the gut microbiome of autistic children in China.
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In recent years, there has been an emerging interest in the possible role of the gut microbiota as a co-factor in the development of autism spectrum disorders (ASDs), as many studies have highlighted the bidirectional communication between the gut and brain (the so-called “gut-brain axis”). Accumulating evidence has shown a link between alterations in the composition of the gut microbiota and both gastrointestinal and neurobehavioural symptoms in children with ASD. The aim of this narrative review was to analyse the current knowledge about dysbiosis and gastrointestinal (GI) disorders in ASD and assess the current evidence for the role of probiotics and other non-pharmacological approaches in the treatment of children with ASD. Analysis of the literature showed that gut dysbiosis in ASD has been widely demonstrated; however, there is no single distinctive profile of the composition of the microbiota in people with ASD. Gut dysbiosis could contribute to the low-grade systemic inflammatory state reported in patients with GI comorbidities. The administration of probiotics (mostly a mixture of Bifidobacteria, Streptococci and Lactobacilli) is the most promising treatment for neurobehavioural symptoms and bowel dysfunction, but clinical trials are still limited and heterogeneous. Well-designed, randomized, placebo-controlled clinical trials are required to validate the effectiveness of probiotics in the treatment of ASD and to identify the appropriate strains, dose, and timing of treatment.
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One of the most common neurodevelopmental disorders worldwide is autism spectrum disorder (ASD), which is characterized by language delay, impaired communication interactions, and repetitive patterns of behavior caused by environmental and genetic factors. This review aims to provide a comprehensive survey of recently published literature on ASD and especially novel insights into excitatory synaptic transmission. Even though numerous genes have been discovered that play roles in ASD, a good understanding of the pathophysiologic process of ASD is still lacking. The protein–protein interactions between the products of NLGN, SHANK, and NRXN synaptic genes indicate that the dysfunction in synaptic plasticity could be one reason for the development of ASD. Designing more accurate diagnostic tests for the early diagnosis of ASD would improve treatment strategies and could enhance the appropriate monitoring of prognosis. This comprehensive review describes the psychotropic and antiepileptic drugs that are currently available as effective pharmacological treatments and provides in-depth knowledge on the concepts related to clinical, diagnostic, therapeutic, and genetic perspectives of ASD. An increase in the prevalence of ASD in Gulf Cooperation Council countries is also addressed in the review. Further, the review emphasizes the need for international networking and multidimensional studies to design novel and effective treatment strategies.