Gastrointestinal dysfunction and autism: caution with misdiagnoses as many mysteries remain to be unraveled!

Introduction

Autism spectrum disorder (ASD) is a nebulous neurodevelopmental disorder that involves deficits in communication skills and social interaction impariment as well as incessant, ritualistic interests and aberrational activities (1), (2). Complicating this complex clinical picture are strong genetic components as well as a variety of co-morbid conditions that may be observed, including aggression, mood disorders, anxiety disorders, attention deficit hyperactivity disorder, and medical disorders such as epilepsy, eczema, headaches, sleep disorders, and gastrointestinal (GI) disorders (1), (2), (3). This treatise considers the potential link between GI disorders and autism that can include abnormal eating patterns.

GI disorders and ASD

GI symptoms and disorders may occur in persons with ASD and some research suggests an increase in these conditions in those with ASD (4), (5), (6).

Such conditions/symptoms include gastroesophageal reflux, abdominal pain, abdominal distension, constipation (fecal incontinence), diarrhea, and gastroenteritis (4), (5), (6), (7), (8). Research, however, has not clearly established whether the prevalence of these conditions is actually increased over that found in the general population (9), (10), (11), (12). Problems in communication can complicate attempts for diagnosis as well as treatment and some research reveals an increase in the reporting of GI symptoms (versus disorders) including diarrhea, constipation, and flatulence (3), (12). The issue of faddiness (i.e. being very fussy about food) is reflective of the ASD diagnosis and not a specific GI symptom or disorder per se (12).

Some research links augmentation in GI disorders with increase in severity of autism, while other studies link GI disorders with an increase in sleep disorders seen in autism as well as a link between food intolerance (non-IgE-mediated food allergy) and GI disturbances (6), (13), (14), (15). A salient study suggests the clustering of GI dysfunction, anxiety, and autonomic dysfunction in some children with ASD (16).

Gut-brain link and ASD

A gut-brain axis defect has been proposed but not proved, in which GI dyfunction may add to ASD pathogenesis and/or symptoms; GI problems may also add to such problems as metabolic abnormalities, hypersertonemia, and/or immunological abnormalites (17). Though some suggest a “leaky gut” in persons with autism, research does not show any differences in intestinal function (i.e. disaccharidase activity, intestinal inflammation, intestinal permeability) between those with and without autism (18).

Secretin is a peptide hormone produced in the S cells of the duodenum that regulates secretions in abdominal organs (i.e. liver, pancreas, and stomach); some research has proposed that secretin may be involved in such a link (19). It has been proposed that some types of GI dysfunction (i.e. disaccharide malabsorption, reflux esophagitis) intensify emotional features of ASD and may be linked with increased pancreaticobilary secretion after secretin is given intravenously (19). Studies, however, have generally not identified improvement in ASD features with secretin administration (20), (21).

Abnormalities in the GI microbiota have been proposed to lead to ASD behavioral features due to the effect of GI production and absorption of various deleterious toxins (22). The microbiota-gut-brain axis is involved in various key biological mechanisms, including the neuroimmne, neuroendocrine, and autonomic nervous systems (23). Abnormalities in this axis may be induced by bacterial infection or prolonged use of antibiotics (23). Improvement in this axis may abate the negative features of ASD and thus, studies are looking at modulators of this axis that include probiotics, special diets, helminthes, and others (23). Some research suggests that use of probiotics may have beneficial effects on persons with ASD, although use of special diets (i.e. casein-free diet, gluten-free diet, supplementation with magnesium or B₆) has not consistently produced efficacious results in ASD symptoms nor have they been proved to be either an elixir or a fetish for ASD (21), (24).

Research continues into a potential gut-brain axis link in ASD (25), (26). Immune dysfunction leading to GI symptoms in persons with ASD remains under study and this includes increased immune respone to dietary proteins and increased production of the proinflammatory agent cytokine (27), (28). Infection is proposed to occur in the pregnant female with toxic effects on the offspring’s central nervous system via an immune system-GI organ connection involving neuropeptide abnormality and other toxic factors (29).

Failure to thrive and ASD

An important and often missed link of gastroenterological problems with ASD persons is the existence of feeding difficulties and failure to thrive (FTT) in infancy that may develop well before the diagnosis of ASD is made. This is a critically important issue because the average age of ASD diagnosis is 5.7 years, though parents may be concerned in this regard as early as 18 months or 24 months of age (30), (31). Indeed, precedent publications are seen describing infants who developed early FTT in infancy with feeding eccentricities and abnormal growth and were eventually diagnosed with ASD (32). Feeding aberations in infants with autism may arise from deficits in various systems in the infant that involve complex emotional, sensory, and cognitive functioning (32).

Cognizant clinicians must exercise extreme caution in not issuing destructive, desultory, diagnostic dictums that arbitrarily assign egregious etiologic “blame” in infants having non-organic FTT because of the complexities and unknown aspects of attachment insecurity, “obiter dictum” infantile anorexia, psychosomatic factors, and abnormal growth status (32), (33), (34), (35), (36). Parental assignment of child abuse charges must be assiduously applied in such situations and only suggested after a thorough evaluation of the infant, including consideration of neurodevelopmental disorders such as ASD (1), (37), (38).

Infants with feeding difficulties, growth abnormalities, and/or overt FTT should be comprehensively and frequently examined for neurodevelopmental disorders such as ASD. These young persons should be examined for early warning signs of autism, such as failing to respond to sounds during the first 2 months after birth, failing to show reciprocal behavior with parents by 4 months of age, failing to initiate interactions that include smiling and imitating behaviors with parents by 9 months of age, and/or evidence of impaired joint attention (2), (39). One of the earliest signs of autism in infancy is abnormal joint attention, in which the infant will not attend to the same object in the milieu that is being attended to by the parent (2), (40). Joint attention is an early social-communicative ability that allows the young child and adult to share attention on interesting objects or events using gestures and gaze (40).

Parents should not be blamed for their child having FTT that eventually is shown to be part of ASD. They should not be involved with child protective services if their infant has FTT and the medical team involved in the infant’s care is not able to identify a cause and misses early signs of ASD or fails to tentatively consider such a diagnosis. They should not have to be extirpately exonerated later after irrevocable parental anger has developed and when the ASD diagnosis is explicily evident to all, as the fallacious faux pas of child neglect should not have been made at all. Mothers were falsely cited as the cause of autism by extenuating experts in the 20th century with the “cold mothers” theory of autism that fueled and inveigled a bête noire attack on vaccinations (41). This anachronistic assault on parents should not re-occur in a damaging déjà vu incubus for mothers in the 21st century, as clinicians and society must be careful when the limits of science are reached, or when subtle features of disease are jauntily missed and iatric, impervious arrogance is fraught with forensic fiascos.

Summary

Ancora imparo (Yet, I am still learning)

Michelangelo di Lodovico Buonarroti Simoni (1475–1564)

Autism is a complex neurodevelopmental disorder with underlying etiologic bases involving genetic, neuroimmunologic, neuroendocrine, and autonomic nervous system complexities (12), (21), (23). Studies continue regarding the concept of the microbiota-gut-brain axis and how it may be utilized to assuage the aversive aspects of ASD (23), (25), (26), (42).

A variety of GI disorders may occur in persons with ASD and though some literature suggests an augmentation of GI disorders in these persons, research has not clearly shown this to be the case in contrast to those without ASD (9), (10), (11), (12), (43). Some behaviors in children with ASD may be suggestive of GI issues and these behaviors include abnormal eating habits in younger or older children, abnormal sleeping patterns, and increased aggression/oppositional behavior (44). Abnormal eating habits that may occur include extreme food selectivity and food neophobia (45).

Eccentric eating habits may begin in infancy long before a diagnosis of ASD is made. Circumspect clinicians must be cautious not to exigently engage in wrongful or poorly advised diagnoses of cursory conjecture in the absence of clear evidence of the cause of the dysfunctional eating patterns. Parents should not be contumely chastised with coercive charges of child neglect or child abuse when complacent clinicians encounter an infant with FTT from unknow origins. FTT can occur in infants long before clear evidence arises to provide a decisive, didactic diagnosis of ASD.