Available online 19 November 2023, 101841

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The gut microbiome has been implicated in a variety of neuropathologies with recent data suggesting direct effects of the microbiome on host metabolism, hormonal regulation, and pathophysiology. Studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, no study to date has examined the specific role of GH on the fecal microbiome (FMB) or the changes in this relationship following a traumatic brain injury (TBI). Current literature has demonstrated that TBI can lead to either temporary or sustained abnormal GH secretion (aGHS). More recent literature has suggested that gut dysbiosis may contribute to aGHS leading to long-term sequelae now known as brain injury associated fatigue and cognition (BIAFAC). The aGHS observed in some TBI patients presents with a symptom complex including profound fatigue and cognitive dysfunction that improves significantly with exogenous recombinant human GH treatment. Notably, GH treatment is not curative as fatigue and cognitive decline typically recur upon treatment cessation, indicating the need for additional studies to address the underlying mechanistic cause.

Section snippetsTraumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability affecting an estimated 64-74 million people worldwide yearly [1]. In 2016, the US Department of Defense defined TBI as “a traumatically induced structural injury and/or physiological disruption of brain function as a result of an external force that is indicated by new onset or worsening of at least one of the following clinical signs immediately following the event: alteration in mental status, loss of memory for events

Abnormal Growth Hormone Secretion (aGHS)

Hypopituitarism as a result of TBI was reported more than 65 years ago [14]. Since that time, there have been numerous studies that have reported significant numbers of patients with post-TBI anterior pituitary dysfunction affecting as many as 40-50% of those with severe TBI [15], [16]. A substantial number of studies examined anterior pituitary hormone levels acutely with a limited number reporting impacts beyond six months (acute phase) following the initial TBI [15].

While the pathophysiology

Brain Injury Associated Fatigue and Altered Cognition (BIAFAC)

BIAFAC syndrome was formally described in 2020 [24]. This syndrome describes patients with a history of TBI of all severities who develop chronic fatigue, brain fog, and sleep difficulties that persist months to years after injury [24]. Diagnostically, maximal GH secretion of <10 ng/mL in response to glucagon stimulation was consistently observed in symptomatic patients [24], hence, a peak response <10 ng/mL was used as a threshold for BIAFAC diagnosis for patients with a history of TBI and

Gut dysbiosis and the Microbiota-Gut-Brain Axis

A new and rapidly expanding field of research suggests that gut bacteria influences brain and endocrine functions via an interaction termed the microbiota-gut-brain axis [48]. This axis (Fig. 2) has been associated with a growing number of neuropathologies and is now understood to exert remarkable control over human health, mood and possibly behavior [48]. Dietary modifications, infections, injuries, and changes to the GI mucosa can shift the gut microbiome to a dysbiotic state with pronounced

Conclusions

Both acute and long-term effects of TBI are a growing public health concern worldwide. TBIs are common in athletes, military personnel as well as in the general population, and can lead to debilitating fatigue, altered cognition, and altered GH secretion as seen in BIAFAC patients. Individuals with BIAFAC find it difficult to perform their jobs or succeed in school and frequently seek alternate positions with less hours or take leaves of absence to accommodate their symptoms. Many BIAFAC

Uncited reference

[25]

Acknowledgements

The figures were created with BioRender.com. Fig. 1 was adapted from the “Anterior Pituitary Hormones” template, Fig. 4 was adapted from the “Metabolism of SCFAs” after retrieval from https://app.biorender.com/biorender-templates.

CONLICT OF INTEREST

The authors have no conflicts of interest to declare related to this publication.

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