Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

I also conclude that this told us nothing that will help stroke survivors. 

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

Denise Battaglini^1,2, Pedro Moreno Pimentel-Coelho³, Chiara Robba¹, Claudia C. dos Santos⁴, Fernanda Ferreira Cruz^5,6, Paolo Pelosi^1,2 and Patricia Rieken Macedo Rocco^5,6*

• ¹Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy
• ²Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
• ³Laboratório de Neurobiologia Comparada e do Desenvolvimento, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
• ⁴Keenan and Li Ka Shing Knowledge Institute, University Health Toronto—St. Michael's Hospital, Toronto, ON, Canada
• ⁵Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
• ⁶Rio de Janeiro Network on Neuroinflammation, Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil

The microbiota–gut–brain axis is considered a central regulator of the immune system after acute ischemic stroke (AIS), with a potential role in determining outcome. Several pathways are involved in the evolution of gut microbiota dysbiosis after AIS. Brain–gut and gut–brain signaling pathways involve bidirectional communication between the hypothalamic–pituitary–adrenal axis, the autonomic nervous system, the enteric nervous system, and the immune cells of the gut. Alterations in gut microbiome can be a risk factor and may also lead to AIS. Both risk factors for AIS and gut-microbiome composition are influenced by similar factors, including diabetes, hypertension, hyperlipidemia, obesity, and vascular dysfunction. Furthermore, the systemic inflammatory response after AIS may yield liver, renal, respiratory, gastrointestinal, and cardiovascular impairment, including the multiple organ dysfunction syndrome. This review focus on biochemical, immunological, and neuroanatomical modulation of gut microbiota and its possible systemic harmful effects after AIS, as well as the role of ischemic stroke on microbiota composition. Finally, we highlight the role of gut microbiota as a potential novel therapeutic target in acute ischemic stroke.

Introduction

Acute ischemic stroke (AIS) is the second leading cause of death worldwide, accounting for up to 25% of global lifetime risk (1). Great effort has been invested into identifying risk factors, elucidating pathogenesis, and discovering implications for outcomes (2). Post-AIS infection has been identified as a key cause of death and prolonged hospitalization after stroke (3). Recent advances have demonstrated, for instance, that peripheral adaptive immunity is activated and recruited into the brain within the first few hours/days after AIS (4), and that its cells might regulate and be regulated by the gut microbiota (5). A microbiota is defined as an ecological unit composed of microorganisms within a specific (micro) environment, while the microbiome is the genetic material of these microorganisms (6). Dysbiosis is defined as a microbial imbalance in composition and function of the microbiota, occurring in several animal models of AIS which demonstrates that gut microbiota can regulate the neuroinflammatory response, influencing brain recovery (7). Several studies have focused on the relationship between the intestinal microbiome and AIS, confirming the existence of a bidirectional microbiota–gut–brain axis (8). In fact, alterations in gut microbiome can be a risk factor for AIS, and vice-versa; AIS may lead to changes in gut microbiome, impacting on peripheral organs and leading to severe liver, renal, respiratory, gastrointestinal and cardiovascular impairment, including the multiple organ dysfunction syndrome (MODS) (9). The aim of this review is to highlight the pathophysiology potentially involved in gut microbiota modulation after AIS, and its implication for therapy and outcome.

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Conclusions

Translational microbiome research against the enhanced systemic inflammatory immune and neuroendocrine responses and on the impact of modulation of the environment, diet, and drugs on the so-called halobiont in AIS patients are limited. Since only few of these studies have demonstrated that antibiotic treatment, probiotics, exercise, or environmental changes could be essential for microbiota and outcome modulation, microbiota dysregulation after AIS remains a challenging target for new therapies.