Chapter Nine - Traumatic spinal cord injury and the contributions of the post-injury microbiome

Spinal cord injuries (SCI) are traumatic occurrences with an annual incidence of roughly 15,000 new cases in the United States, and almost half a million world-wide (Lee, Cripps, Fitzharris, & Wing, 2014). Due largely to injuries resultant from ground transportation incidents or falls (Lee et al., 2014), SCI leads to life-long impairment across numerous body systems. It further imposes an enormous mental, physical, and financial burden on the injured individual and their caregivers. In the US, estimates of financial costs that individuals and their caregivers will incur over the post-injury lifetime is $1.2–$5 million per person, excluding lost wages, in conjunction with significant decreases in overall quality of life (Lee et al., 2014).

Injuries themselves are highly variable in their etiology (e.g., contusion, transection, etc.) severity (e.g., depth of contusion, duration of compression/distraction, completeness of severance) and level of injury (e.g., cervical, thoracic, lumbar). These etiological factors lead to a wide range of both primary injury phenotypes and secondary sequelae. Certainly, para- and tetraplegia are visible, well-known, and debilitating indications of SCI, however dysfunction in the gastrointestinal (GI), genitourinary, and cardiac systems are also apparent both acutely and chronically following SCI (Ahuja et al., 2017; Alizadeh, Dyck, & Karimi-Abdolrezaee, 2019; Simpson et al., 2012). Further, long term effects on mood disorders and somatosensation (i.e., nociception) arise (Craig, Guest, Tran, & Middleton, 2017; Jurkiewicz, Crawley, Verrier, Fehlings, & Mikulis, 2006; Khazaeipour, Taheri-Otaghsara, & Naghdi, 2015).

Given the broad and systemic effects of SCI across physiological systems, emerging studies in the last 5–6 years have begun to examine potential contributions of the indigenous microbiome to SCI recovery. As the microbiome has established capacity to modulate inflammatory and metabolic responses (Fung, Olson, & Hsiao, 2017), two critical players in setting the tone of SCI recovery, it is likely that microbiome-dependent activities impart effects on recovery. In fact, a number of recent experimental studies establish concrete associations with microbiome-mediated contributions to recovery after SCI in rodent models.

Additionally, a wide array of intrinsic GI dysfunctions (e.g., neuropathy) are observed acutely following injury (Holmes & Blanke, 2019). We, and others, predict that these acute alterations to GI physiology drive changes to the structure of the microbiome. Across both animal models and human incidences of SCI, shifts in particular microbial taxa of the gut microbiome have been observed (Bannerman, Douchant, Sheth, & Ghasemlou, 2021; Bannerman, Douchant, Segal, et al., 2021; Bazzocchi et al., 2021, Cheng et al., 2021, Doelman et al., 2021, Du et al., 2021; Gungor et al., 2016; Jing et al., 2019; Jing, Bai, & Yu, 2021; Jing et al., 2021, Jing et al., 2022; Jogia & Ruitenberg, 2020; Kigerl et al., 2016; Kigerl, Mostacada, & Popovich, 2018; Kigerl, Zane, Adams, Sullivan, & Popovich, 2020; Li et al., 2020, Li et al., 2021; Li, Morrow, McLain, Womack, & Yarar-Fisher, 2022; Lin et al., 2020; Musleh-Vega, Ojeda, & Vidal, 2022; Myers et al., 2019; O’Connor et al., 2018; Panther, Dodd, Clark, & Lucke-Wold, 2022; Rong et al., 2021, Schmidt et al., 2020, Schmidt et al., 2021; Schmidt, Raposo, Madsen, et al., 2021; Valido et al., 2022, Wallace et al., 2019, Yu et al., 2021; Yuan, Lu, & Wu, 2021; Zhang et al., 2018, Zhang et al., 2019). This dysbiosis (a detrimental disruption to the microbiome community) has the capacity to feed into the physiological pathways that impact recovery following injury. From these emerging observational and experimental studies, a more complete picture of SCI recovery is being developed. The drastic and acute, whole-body, physiological dysfunctions that arise following SCI trigger disturbances in the intestinal environment, influencing both the composition and functionality of the microbiome. As microbiome structure and activities change, altered detrimental signals derived from this dysbiotic community differentially modulate inflammatory activation and metabolic input across all body systems, leading to effects on recovery both within and outside the spinal cord.

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