The biological rationale for combining abdominal and transcranial photobiomodulation rests on the fact that near-infrared light in the 1064-nm range penetrates tissue more deeply than shorter wavelengths, reaching both cortical neurons through the skull and abdominal organs through the intervening layers of skin, fat, and muscle. At the cellular level, the primary photoacceptor for this light is cytochrome c oxidase, the terminal enzyme of the mitochondrial electron transport chain. When photons of appropriate wavelength are absorbed by this enzyme, the proposed effect is a reduction in the inhibitory state of the complex, allowing electron transport to proceed more efficiently. This can increase adenosine triphosphate production, modulate the release of reactive oxygen species at low signaling levels, and trigger downstream changes in gene expression, nitric oxide signaling, and cellular stress responses. Because mitochondria are abundant in metabolically active tissues, including neurons, enteric glia, and the epithelial lining of the gastrointestinal tract, the same physical mechanism can plausibly operate at both anatomical sites targeted in this protocol.

The gut-brain axis provides a conceptual bridge between these two stimulation sites. The enteric nervous system contains hundreds of millions of neurons embedded in the intestinal wall, and it communicates bidirectionally with the central nervous system through the vagus nerve, the sympathetic and parasympathetic pathways, circulating hormones, and immune mediators. Microbial metabolites, particularly short-chain fatty acids such as butyrate, propionate, and acetate, are known to influence this axis by strengthening epithelial barrier function, modulating immune cell differentiation, and crossing the blood-brain barrier to affect neuronal metabolism. The taxa observed in the post-intervention sample, including Faecalibacterium, Bifidobacterium, Bacteroides, and Akkermansia, are all associated with aspects of this metabolic and immunological dialogue. Faecalibacterium, for example, is one of the most abundant butyrate producers in the healthy human gut, and reduced abundance of this genus has been reported in inflammatory and neurobehavioral conditions. Bifidobacterium species are associated with mucosal adhesion and immune modulation, while Akkermansia muciniphila is a mucin-degrading organism linked to barrier integrity and metabolic health.

The shift from a baseline sample dominated by unclassified sequences to a post-intervention sample with a well-resolved taxonomic profile is itself a notable observation. In 16S rRNA amplicon sequencing, the fraction of reads that cannot be assigned to a known taxon depends on the quality of the sequencing run, the reference database used, and the actual composition of the sample. A baseline dominated by unclassified reads can reflect technical limitations, but it can also reflect a microbial community composed of organisms poorly represented in reference databases, or a community whose DNA was degraded by prolonged intestinal transit, as occurs in chronic constipation. When stool transit slows, the microbial community is exposed to altered pH, altered oxygen tension, and altered substrate availability, all of which can shift the balance toward taxa that thrive under these conditions. The improvement in bowel regularity reported by caregivers during the intervention may therefore have contributed to the change in taxonomic resolution, either as a mediator of the microbial shift or as a parallel consequence of the same underlying physiological change.

The constipation itself deserves attention as a potential driver of the baseline microbial profile. Chronic constipation is associated with prolonged colonic transit time, increased water absorption, and a shift in the dominant fermentation patterns within the gut lumen. Studies of constipated individuals have reported reduced abundance of butyrate-producing taxa and increased representation of taxa associated with protein fermentation, which produces metabolites such as ammonia, branched-chain fatty acids, and indoles that can be irritating to the epithelium. If the PBM protocol improved motility through any mechanism, whether through direct effects on enteric neurons, effects on smooth muscle energy metabolism, or effects on autonomic tone via the prefrontal cortex, the resulting change in transit could have reshaped the microbial ecology independently of any direct photobiomodulation effect on the microbes themselves. This distinction between direct and indirect mechanisms is one of the central interpretive challenges in this case report.

The transcranial component of the protocol introduces additional mechanistic possibilities. The right prefrontal cortex, the target used here, has been studied in the context of autonomic regulation, and stimulation of this region has been associated with changes in heart rate variability, vagal tone, and sympathetic-parasympathetic balance. The vagus nerve provides a direct anatomical connection between the brainstem and the gastrointestinal tract, and it also carries afferent signals from the gut to the brain. Vagal signaling is known to influence gut motility, secretion, and immune function, and it has been implicated in the communication between the microbiome and the central nervous system. If transcranial PBM modulated prefrontal activity in a way that altered autonomic output to the gut, this could have influenced intestinal transit, mucosal blood flow, and the local inflammatory environment, all of which are relevant to microbial community composition.

The medication context of this patient is also relevant to the interpretation of the microbiome findings. Risperidone, an antipsychotic, is known to affect gastrointestinal motility and has been associated with changes in metabolic parameters. Oxcarbazepine, an anticonvulsant, can affect hepatic metabolism and may have indirect effects on the gut environment. Guanfacine, an alpha-2 adrenergic agonist, affects sympathetic tone and can influence gastrointestinal function. Because these medications were held constant throughout the 90-day protocol, they do not explain the temporal change in the microbiome, but they do contribute to the baseline microbial state and may have shaped which taxa were present or absent at the start of the intervention. The absence of probiotic use during the protocol is a useful detail, as it reduces the likelihood that the observed changes were driven by exogenous microbial introduction.

The choice of 1064 nanometers as the wavelength for this protocol is grounded in the optical properties of biological tissue. This wavelength falls within what is sometimes called the optical window, a range in which absorption by water, hemoglobin, and melanin is relatively low, allowing deeper tissue penetration than shorter visible wavelengths. At the same time, 1064 nanometers is within the absorption spectrum of cytochrome c oxidase, making it effective for the proposed mitochondrial mechanism. The irradiance used, 54 milliwatts per square centimeter, is within the range commonly used in clinical and experimental PBM studies, and the total dose delivered in each session, approximately 32 joules per square centimeter over 10 minutes at each site, falls within parameters that have been reported as safe in prior investigations.

The observation that the intervention was well tolerated without reported adverse effects is consistent with the broader safety profile of PBM in the literature. Near-infrared light at these parameters does not cause thermal damage at the doses used, and the non-ionizing nature of the light means that it does not carry the risks associated with ionizing radiation. However, the absence of adverse effects in a single patient over 90 days does not establish safety for all populations, particularly for pediatric patients with complex neurodevelopmental and genetic conditions. The presence of a rare TUBB2A variant in this patient raises questions about whether her neurodevelopmental phenotype and her microbial ecology might both be influenced by underlying genetic factors that are independent of the intervention.

The field of microbiome research has increasingly recognized that single time-point comparisons are vulnerable to the substantial day-to-day variability that exists in gut microbial communities. Factors such as sleep, stress, physical activity, hydration, and even the time of day of sample collection can influence the relative abundance of specific taxa. Without repeated baseline sampling, it is impossible to know whether the baseline sample in this case was representative of the patient’s typical microbial state or whether it was an atypical snapshot. Similarly, without longitudinal follow-up after the intervention, it is unknown whether the post-intervention profile would persist, revert, or continue to evolve. These limitations are acknowledged by the authors and are important for calibrating expectations about what this case report can and cannot demonstrate.

The systems biology framing of this report is worth considering in a broader context. Rather than isolating a single mechanism, the systems approach acknowledges that PBM may simultaneously influence mitochondrial function, vascular dynamics, inflammatory signaling, autonomic regulation, and microbial ecology, and that these pathways interact in ways that cannot be fully disentangled by studying any one of them in isolation. The gut microbiome is not merely a passive target of such interventions but may itself be an active participant in the systemic response, producing metabolites and signaling molecules that feed back into host physiology. This perspective suggests that future studies should measure multiple domains simultaneously, including microbial composition, metabolomic profiles, inflammatory markers, autonomic metrics, and behavioral outcomes, to begin to map the network of interactions that may underlie the clinical observations described here.

The specific taxa observed in the post-intervention sample invite comparison with findings from other studies of neurobehavioral conditions. Reduced Faecalibacterium abundance has been reported in some studies of autism spectrum disorder, as has altered Bacteroides representation. Increased Akkermansia has been associated with improved mucosal integrity in some contexts, though its role is context-dependent and can vary with overall community structure. The presence of Collinsella, which has been associated with pro-inflammatory activity in some studies, and Sarcina, which is less commonly discussed in the context of the human gut, illustrates the complexity of interpreting individual taxa without considering the full community context. The transparent reporting of taxa with uncertain significance is a methodological strength, as it avoids the selective emphasis on favorable findings that can occur in single-case reports.

Looking forward, the most informative next steps would involve controlled studies with multiple participants, repeated sampling at multiple time points before, during, and after the intervention, and integration of microbiome data with metabolomic, immunological, and behavioral measures. Such studies would help distinguish whether the microbial changes observed here are a direct consequence of photobiomodulation, an indirect consequence of improved gastrointestinal function, or a combination of both. They would also help determine whether specific microbial signatures predict or correlate with specific behavioral outcomes, which would be a step toward identifying the mechanisms that connect light-based interventions to neurobehavioral regulation through the gut-brain axis.

Subject of Research: Effects of combined abdominal and transcranial photobiomodulation on the fecal microbiome in a child with autism spectrum disorder

Article Title: Combined abdominal and transcranial photobiomodulation is associated with fecal microbiome restructuring: a systems microbiology pre-post case report

Article References: Combined abdominal and transcranial photobiomodulation is associated with fecal microbiome restructuring: a systems microbiology pre-post case report. (n.d.). https://doi.org/10.3389/fsysb.2026.1920618

Image Credits: AI Generated

DOI: 10.3389/fsysb.2026.1920618

Keywords: photobiomodulation, gut-brain axis, fecal microbiome, autism spectrum disorder, 16S rRNA sequencing, near-infrared light, short-chain fatty acids, constipation, case report, microbiome, Combined, abdominal