Potential mechanisms and research progress of animal-assisted interventions for autism spectrum disorder

Table 2 Potential mechanisms of animal-assisted intervention in improving autism spectrum disorder: Evidence sources and classification

Mechanistic dimension	Specific pathway	Evidence type	Key findings and corresponding effects	Ref.
Neurobiological mechanisms	HPA axis regulation (cortisol reduction)	Direct evidence	AAI (e.g., equine-assisted and dog-assisted interventions) significantly reduces salivary cortisol levels in individuals with ASD and improves stress and irritability symptoms	[18,99,105,121]
	Oxytocin system activation	Theoretical inference	Based on changes in oxytocin-related hormonal responses and social reward functions, AAI is proposed to enhance social motivation and prosocial behaviors through oxytocin system activation	[14,18,99,125-127]
	Prefrontal cortex and social brain network remodeling	Direct evidence	Neuroimaging and EEG studies indicate that dog-assisted therapy and social training increase prefrontal activation and improve α/δ-band connectivity	[48,128,131,132]
	Synaptic remodeling and mirror neuron system activation	Theoretical inference	Dynamic behaviors of live animals may activate the mirror neuron system; exercise-based AAI may enhance the BDNF/mTOR pathway, promoting synaptic remodeling and action understanding	[15,30,135,142,143,145]
Physiological, immune, and metabolic mechanisms	Autonomic nervous system regulation (HRV enhancement)	Direct evidence	Horse riding and interaction with live dogs significantly increase HRV sample entropy, enhance parasympathetic activity, and stabilize emotional states	[19,39,44,45,76]
	Chronic neuroinflammation and cytokine regulation	Theoretical inference	Based on Th1/Th17 polarization and abnormal pro-inflammatory cytokines (IL-6, TNF-α) in ASD, AAI is proposed to suppress inflammatory responses through environmental enrichment effects	[135,142,149,152,156,158,161]
	Mitochondrial function and metabolic homeostasis restoration	Theoretical inference	Based on mitochondrial stress and abnormal lactate metabolism in ASD, combined with exercise-related effects, AAI may indirectly promote mitochondrial biogenesis and energy metabolic balance	[67,142,159-162,165]
Psychological and behavioral mechanisms	Establishment of safety and anxiety reduction	Direct evidence	Therapy dogs and horses provide non-judgmental companionship and deep-pressure tactile stimulation, rapidly reducing emotional stress, fear, and anxiety	[1,18,24,28,76,78,99,168]
	Enhancement of social motivation and active social engagement	Direct evidence	Animals act as “social catalysts”, significantly increasing spontaneous eye contact, verbal/non-verbal communication, and social initiation in children with ASD	[19,22,100,109,143,116,170]
	Behavioral synchrony and positive behavior shaping	Direct evidence	AAI improves motor and verbal synchrony between individuals with ASD and animals/therapists, reducing irritability, hyperactivity, and repetitive behaviors	[25,30,31,49,58,105,113]
	Consolidation of emotional regulation and self-control	Direct evidence	AAI enhances self-control and self-soothing abilities, reduces emotional outbursts, and a 16-week equine intervention significantly improves self-control scores	[1,18,24,64,88,99,107,176]
Sensorimotor integration mechanisms	Vestibular and proprioceptive input (equine-assisted intervention)	Direct evidence	Three-dimensional rhythmic movement from horses provides continuous vestibular and proprioceptive stimulation, significantly improving BOT-2 scores, balance, gross and fine motor skills, and postural control	[3,15,37,39,40,61,67,166,181,182]
	Multimodal sensory input and sensory integration	Direct evidence	Deep-pressure tactile stimulation from dogs and tactile/acoustic stimulation from dolphins improve multisensory integration and enhance adaptive responses to environmental stimuli	[10,14,18,19,30,48,135]

HPA: Hypothalamic-pituitary-adrenal; AAI: Animal-assisted intervention; ASD: Autism spectrum disorder; EEG: Electroencephalogram; mTOR: Mammalian target of rapamycin; BDNF: Brain-derived neurotrophic factor; HRV: Heart rate variability; IL: Interleukin; TNF-α: Tumor necrosis factor-α; BOT-2: Bruininks-Oseretsky Test-2^nd Edition.