Alterations of the GH/IGF-I Axis and Gut Microbiome after Traumatic Brain Injury: A New Clinical Syndrome?

Abstract

Context Pituitary dysfunction with abnormal GH secretion and neurocognitive deficits are common consequences of traumatic brain injury (TBI). Recognizing the comorbidity of these symptoms is of clinical importance; however, efficacious treatment is currently lacking. Evidence Acquisition A review of studies in PubMed published between January 1980 to March 2020 and ongoing clinical trials was conducted using the search terms “growth hormone,” “traumatic brain injury,” and “gut microbiome.” Evidence Synthesis Increasing evidence have implicated the effects of TBI in promoting an interplay of ischemia, cytotoxicity and inflammation that renders a subset of patients to develop post-injury hypopituitarism, severe fatigue, impaired cognition and behavioral processes. Recent data have suggested an association between abnormal GH secretion and altered gut microbiome in TBI patients, thus prompting the description of a hypothesized new clinical syndrome called “Brain Injury Associated Fatigue and Altered Cognition” (BIAFAC). Notably, these patients demonstrate distinct characteristics to those with GH deficiency from other non-TBI causes in that their symptom complex improves significantly with recombinant human GH treatment, but does not reverse the underlying mechanistic cause as symptoms typically recur upon treatment cessation. Conclusion The reviewed data describes the importance of alterations of the GH/IGF-I axis and gut microbiome after brain injury and its influence in promoting neurocognitive and behavioral deficits in a bi-directional relationship, and highlight a new clinical syndrome that may exist in a subset of TBI patients in whom recombinant human GH therapy could significantly improve symptomatology. More studies are needed to further characterize this clinical syndrome.

Gut microbiome depletion and repetitive mild traumatic brain injury differentially modify bone development in male and female adolescent rats

“…This is consistent with another study that found a reduction in bone formation rate and a reduction in bone mass following RmTBI in 10-week-old female mice ( Kesavan et al, 2017 ). Dysregulated bone development following RmTBI occurs in response to disruptions in the GH/IGF-1 axis ( Kesavan et al, 2017 ; Yuen et al, 2020 ). IGF-1 which acts downstream of GH, is responsible for the anabolic processes of growth and development throughout life ( Wrigley et al, 2017 ), particularly longitudinal bone growth ( Olson et al, 2011 ).…”

Nutrition in the Neurocritical Care Unit: a New Frontier

“…The dysbiosis worsens and shifts toward more pathogenic microbiota with longer ICU duration [80][81][82][83]. This has also been demonstrated in neurocritical care populations, including animal and human models of TBI and spinal cord injury [84][85][86]. It has been suggested that serial changes in the ratios of beneficial species of Firmicutes/Bacteroidetes can potentially predict patient outcomes [80].…”

Integrated Proteome and Phosphoproteome Analyses Reveal Early- and Late-Stage Protein Networks of Traumatic Brain Injury

“…Regulation of IGF transport and uptake-related proteins were the most important interacting protein classes that were presented both in group 1d/C and 7d/C of DEPs (Supplementary Figure S4), suggesting it may serve as a therapeutic target for early injury and late restoration. Recent research shows that growth hormone (GH) and IGF de ciency after TBI may inhibit the recovery of the axon and neurons, and thus GH/IGF-I system would be bene t for the therapy of TBI [17][18][19] .…”