TO THE EDITOR
Perianal disease encompasses a spectrum of debilitating conditions that affect the perianal region, including hemorrhoids, fistulas, abscesses, anal fissures, perianal manifestations of Crohn’s disease, pilonidal sinuses, rectal prolapse, anal warts, perianal dermatitis, and rare conditions, such as perianal Paget’s disease and anal stricture. Notably, perianal fistulas and abscesses are common complications of Crohn’s disease. It is estimated that 1 in 5 individuals with Crohn’s disease will develop some form of perianal disease within the first 10 years of diagnosis, with most cases eventually requiring surgical intervention[1].
The impact of these conditions extends beyond physical symptoms, involving not only pain and fecal incontinence, but also significant social stigma and a substantial reduction in health-related quality of life (HR-QoL)[2], often necessitating surgery. However, post-surgical recovery is influenced by more than just biological factors[3]. Emerging research highlights the critical role of psychoneuroimmunoendocrine (PNIE) pathways in regulating recovery outcomes[4].
A key mediator in these pathways is the gut microbiota, a complex and dynamic community of micro-organisms that plays a vital role in maintaining immune balance. The gut microbiota influences emotional and psychological states[5], as well as post-surgical outcomes[6]. Recognizing the connection between the brain, gut microbiota, and wound healing offers an opportunity to address both mental and physical health in postoperative care. This underscores the potential benefits of modulating the microbiota and incorporating mental health screening as part of a comprehensive approach to enhancing recovery outcomes.
In this letter, we aim to broaden the understanding of how illness perception and negative emotional states affect post-surgical recovery. We discuss the findings of Hou et al[7] in their study, “Correlation Linking Illness Perception, Negative Emotions, and the Post-Operative Recovery Effect in Patients with Perianal Disease,” which offers key insights into the interaction between psychological factors and physical healing in patients with perianal disease.
PNIE pathways and the gut microbiota
The PNIE pathways demonstrate how the mind, brain, immune system, and hormones collectively regulate the body’s responses to stress, inflammation, and healing. Within this network, the gut microbiota plays a crucial role in maintaining physiological balance. Increasing evidence highlights its influence beyond immune function, particularly in neuropsychiatric conditions, cognitive processes, behavior, and emotional regulation.
Recent research has established strong links between the gut microbiota and conditions, such as anxiety, depression, and stress-related disorders[8]. These connections are mediated by microbiota-produced metabolites and neurotransmitters that interact with the central nervous system via the gut–brain axis[9,10], influencing both emotional and physiological responses to recovery.
Gut microbiota’s role in wound healing and inflammation
The gut microbiota is crucial for regulating immune responses and promoting tissue repair, both of which are essential for postoperative recovery. An imbalance in gut bacteria (dysbiosis) has been linked to impaired immune function and increased systemic inflammation, which can delay wound healing[11,12].
For patients with perianal disease, who already face a heightened risk of post-surgical complications, maintaining a healthy gut microbiota is even more critical. Dysbiosis, exacerbated by surgical stress, antibiotics, and dietary changes, can impair the immune system’s ability to control inflammation, prolonging recovery, and increasing the risk of infection.
Although the link between the gut microbiota and anorectal diseases is still under-researched, emerging evidence underscores the microbiota’s influence on immune modulation and tissue repair[13]. The gut–skin axis, a communication network between the gut and skin, further supports this connection, with the mechanisms of communication described in detail elsewhere[14].
In addition to the gut microbiota, the wound microbiota[15] and mental health also play key roles in recovery. Dysbiosis affects both physical and psychological wellbeing via the gut–brain axis, contributing to conditions, such as anxiety and depression, which in turn, further exacerbate dysbiosis, potentially compromising immune function and healing. Therefore, optimizing gut health and mental health is essential to improve recovery outcomes, particularly after surgery.
ILLNESS PERCEPTION AND PSYCHOLOGICAL FACTORS AFFECTING RECOVERY
Traditionally, recovery has been viewed through a purely biological lens, with psychological factors considered to impact health only indirectly, primarily through behavior. However, research suggests that individual perception can directly influence physiological outcomes.
An outstanding study by Aungle and Langer[16] demonstrated that wound healing can be influenced by an individual’s perception of time. Remarkably, wounds healed faster when individuals felt more time had passed, and slower when they perceived less time, despite the actual time elapsed remaining constant. This challenges conventional medical understanding and underscores how psychological states—such as individual illness perception and recovery—can tangibly affect biological processes like healing.
Illness perception itself can significantly influence pain, HR-QoL, and overall health outcomes[17], with some studies noting differences between sexes[18]. Patients who perceive their illness more negatively tend to experience slower recovery or worse outcomes, even when medical severity is the same. This highlights the critical role of psychological factors—such as patients’ attitudes, beliefs, and perceptions about their illness, family support, and their relationship with healthcare providers—in shaping treatment adherence and influencing physiological recovery[19].
Effective management of perianal disease requires a holistic approach that incorporates psychological and social dimensions of care. Addressing patients’ perceptions and attitudes toward their illness, along with comprehensive education, is essential. Equally important is the need for targeted medical training to reduce the stigma surrounding perianal conditions. By fostering a more empathetic and supportive healthcare environment, these interventions can mitigate negative emotions, enhance adherence to postoperative care, and ultimately lead to better long-term recovery outcomes.
NEGATIVE EMOTIONS AND MICROBIOTA: IMPACT ON POSTOPERATIVE RECOVERY
The gut microbiota is closely linked to emotions, producing metabolites that influence anxiety, depression, and other negative feelings. Ke et al[5] found that negative emotions were associated with higher levels of specific gut bacteria, such as Firmicutes bacterium CAG 94 and Ruminococcaceae, while positive emotions corresponded to lower levels.
Studies have identified distinct microbial clusters, known as enterotypes, which differ in their relative levels of bacterial families, such as Bacteroides, Prevotella, and Ruminococcus. These enterotypes have been linked to specific emotional responses and neural connectivity patterns in brain regions responsible for emotional regulation, attention, and sensory processing. For example, individuals with a “Prevotella-high” enterotype tend to exhibit heightened affective responses, while other microbial profiles have been associated with both positive and negative emotional states[20]. This emphasizes the broader influence of the gut microbiota on mental health and behavior, potentially shaping individual responses to illness.
Chronic stress and negative emotions activate the hypothalamic-pituitary-adrenal (HPA) axis, raising cortisol levels and causing stress-induced dysbiosis. This dysbiosis worsens emotional states and impairs immune function, delaying wound healing and increasing infection risk. In postoperative recovery, especially for patients with perianal disease, this creates a cycle where emotional and microbial health are both crucial for optimal healing.
This connection between negative emotions and the gut microbiota highlights the potential role of diet and lifestyle interventions, probiotics[21,22], psychobiotics[23,24], and other microbiota-modulating therapies[25] in wound healing. Although scientific evidence is still emerging, it is likely that in the coming years, we will see increasing research and application in this area.
IMPLICATIONS FOR POSTOPERATIVE CARE
Understanding the interplay between PNIE pathways, the gut microbiota, and illness perception offers a new perspective on postoperative care for patients with perianal disease. A holistic approach that addresses both psychological and microbial health could significantly improve recovery outcomes.
Psychological interventions, including clinical hypnosis, cognitive-behavioral therapy (CBT), mindfulness practices, and psychodynamic or interpersonal therapies, play a critical role in enhancing postoperative recovery by modulating brain function and the microbiota–gut–brain axis[26,27]. Clinical hypnosis and neurofeedback improve emotional regulation by alleviating stress, pain, and anxiety. Mindfulness practices, including meditation and breath-focused exercises, foster psychological flexibility and promote acceptance, helping patients manage distress and discomfort. CBT facilitates adaptive coping through the restructuring of constructs and maladaptive thought patterns, while acceptance and commitment therapy strengthens emotional resilience by aligning behavior with personal values and recovery goals. Psychodynamic, interpersonal, and “third wave” therapies address underlying psychological and relational issues, supporting emotional adjustment and sustained mental wellbeing throughout the recovery process[28]. Beyond psychological improvements, these interventions induce meaningful neurostructural changes that can enhance cognitive and emotional regulation. Research demonstrates increased connectivity between prefrontal and limbic regions, enhanced hippocampal volume, and improved modulation of the amygdala and anterior cingulate cortex. These neuroplastic adaptations bolster the brain’s ability to regulate emotions, control stress responses, modulate pain, and reduce inflammation, playing a critical role in optimizing long-term recovery and postoperative outcomes[29,30].
Digital mental health interventions can complement these strategies by offering scalable, accessible, and personalized support for recovery. Mobile apps, teletherapy, and online platforms enable continuous access to therapeutic tools, providing real-time monitoring of emotions and behaviors, and tracking recovery progress[31]. Noninvasive brain stimulation targets dysfunctional neural circuits, facilitating durable neuroplastic adaptations[30]. Lastly, identifying patients who may benefit from the use of antidepressants, antipsychotics, mood stabilizers, and other neuromodulators is also key, as these can reduce inflammatory states, potentially improving postoperative outcomes and overall health[32].
Patients with perianal disease can benefit from personalized strategies that balance microbiome health and emotional wellbeing. As research on the gut–brain axis progresses, integrating microbiota-targeted therapies with psychological interventions presents promising opportunities for improving recovery, as highlighted by Panduro et al[33].
The modulation of the microbiota through lifestyle interventions, psychotherapy, prebiotics, probiotics, synbiotics, postbiotics, psychobiotics[34], and fecal microbiota transplantation[35], along with emerging approaches, such as live biotherapeutic products and phage therapy, opens new and promising avenues for both research and clinical innovation. The integration of multiomics[36] will facilitate a deeper understanding of the intricate relationships between the microbiome, physiological processes, and emotional states, paving the way for transformative discoveries. As artificial intelligence continues to evolve, we will gain deeper insights into its potential applications in the understanding and management of emotions, neuropsychiatric disorders[37], and perianal diseases[38,39].
The study by Hou et al[7] highlights the strong link between the psychological factors of illness perception, anxiety, and depression, and post-surgical recovery in patients with perianal disease. Despite the significant impact of emotional distress on recovery, it often goes unaddressed in this patient population. In addition to the potential benefits of gut microbiota modulation, psychological interventions have been shown to influence brain function and microbial composition. By reducing inflammation, promoting beta-endorphin release[40], and regulating HPA axis activation, these therapies can help disrupt the cycle of emotional distress and dysbiosis, ultimately enhancing both mental and physical wellbeing[41], with the potential to significantly improve post-surgical recovery in patients with perianal disease.
Finally, cultural differences must be carefully considered, as they significantly influence the stigma, psychological burden, and clinical trajectory of perianal diseases. In many Western societies, improved access to medical information and increased mental health advocacy have fostered early intervention and greater social acceptance. In contrast, some Eastern cultures regard discussions about these conditions as socially inappropriate, reinforcing privacy norms that delay diagnosis, exacerbate disease progression, and amplify mental health challenges.
A more comprehensive understanding of these cultural dynamics is essential to develop personalized, patient-centered care strategies. However, current research on these sociocultural factors is limited, hindering efforts to effectively address such disparities. Culturally sensitive healthcare approaches, tailored to the distinct needs and beliefs of diverse populations, are vital to improve clinical outcomes and advance equity in healthcare delivery.
CONCLUSION
The relationship between illness perception, negative emotions, and postoperative recovery in patients with perianal disease is deeply interconnected through PNIE pathways and the gut microbiota. Negative emotions and maladaptive illness perceptions can disrupt the gut–brain axis, leading to dysbiosis, inflammation, and delayed healing. A comprehensive approach that integrates psychological support with gut microbiota modulation offers a promising avenue to enhance recovery and overall outcomes. Future research should further investigate this integrative model to optimize postoperative care and improve the quality of life in patients with perianal disease.
ACKNOWLEDGEMENTS
We extend our gratitude to Gusti Gould for enhancing the English quality of this manuscript.
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: Mexican Association of Neurogastroenterology and Motility; Mexican Association of Gastroenterology.
Specialty type: Psychiatry
Country of origin: Mexico
Peer-review report’s classification
Scientific Quality: Grade C
Novelty: Grade C
Creativity or Innovation: Grade B
Scientific Significance: Grade B
P-Reviewer: Bi B S-Editor: Qu XL L-Editor: Filipodia P-Editor: Zhao S
