Ischemic stroke and concomitant gastrointestinal complications- a fatal combination for patient recovery

Abstract

Stroke is primarily a neurodegenerative disease but can also severely impact the functions of other vital organs and deteriorate disease outcomes. A malfunction of the gastrointestinal tract (GIT), commonly observed in stroke patients, is often characterized by severe bowel obstruction, intestinal microbiota changes and inflammation. Over-activated immune cells after stroke are the major contributors to endorse intestinal inflammation and may induce damage to single-layer epithelial cell barriers. The post-stroke leakage of intestinal barriers may allow the translocation and dissemination of resident microflora to systemic organs and cause sepsis. This overshooting systemic immune reaction fuels ongoing inflammation in the degenerating brain and slows recovery. Currently, the therapeutic options to treat these GIT-associated anomalies are very limited and further research is required to develop novel treatments. In this mini-review, we first discuss the current knowledge from clinical studies and experimental stroke models that provide strong evidence of the existence of post-stroke GIT complications. Then, we review the literature regarding novel therapeutic approaches that might help to maintain GIT homeostasis and improve neurological outcomes in stroke patients.

The Role of Gut Microbiota in Cerebrovascular Disease and Related Dementia

“…An increase in gut permeability may lead to bacterial translocation, promoting the passage of bacteria and of excessive microbial metabolites into blood which may reach peripheral tissues such as liver, spleen, kidney, and lung. In fact, bacterial translocation has been observed after stroke and it is believed to contribute to post-stroke infections (Caso et al, 2009;Stanley et al, 2016;Tuz, Hasenberg, Hermann, Gunzer, & Singh, 2022;Wen et al, 2019). But even in the absence of translocation, the leaky gut may result in an increase of microbial metabolites in the blood such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), indoles, kynurenines, and different neurotransmitters which cannot be efficiently removed by the liver and then might directly affect the CNS.…”

“…Gastrointestinal dysfunction such as nausea, dysphagia and defecatory problems are also common symptoms in different neurodegenerative disorders like Parkinson's disease (PD) and multiple sclerosis (MS), (Morais et al, 2021). Post-stroke intestinal ileus is one of the complications observed in stroke patients (Tuz et al, 2022). A recent study provided genetic insight into the gut-brain relationship, implicating shared but non-causal genetic susceptibility of disorders affecting GIT with AD's risk (Adewuyi, O'Brien, Nyholt, Porter, & Laws, 2022).…”

“…Extensive brain injury impairs gastrointestinal function: Several studies have demonstrated gastrointestinal disturbances in stroke patients such as dysphagia, gastrointestinal bleeding, or constipation (Tuz et al, 2022). A common post-stroke complication affecting the gut, which is a major contributor to stroke outcome, disability, and mortality, is the so-called paralytic intestinal ileus or post-stroke ileus, which is characterized by abdominal distension and absent bowel sounds causing a reduced gastrointestinal motility, associated with overgrowth of intestinal bacteria and subsequent dysbiosis.…”

Connecting the Dots: The Interplay Between Stroke and the Gut-Brain Axis

“…Dysphagia, or difficulty in swallowing, is a common stroke complication that can lead to pneumonia and other adverse outcomes [ 12 ]. Furthermore, stroke can cause changes in gut motility and microbiota composition, which can contribute to complications like infections and malnutrition after stroke [ 13 ]. The gut-brain axis is believed to play a critical role in stroke pathophysiology, and hence targeting it may represent a potential therapeutic approach to reduce the morbidity and mortality associated with stroke [ 14 ].…”

The interaction between intestinal microenvironment and stroke

“…It has been established that after a stroke, up to 50% of patients develop gastrointestinal complications, including intestinal motility disorders, dysphagia, fecal incontinence, leaky gut, intestinal bleeding, and even enterogenic sepsis 5,6 . Stroke patients with gastrointestinal complications often have poor prognoses, increased mortality, and worsening neurological function 7,8 . The past decade has witnessed significant inroads achieved in the development of genomics, metabolomics, and proteomics, enabling research on the connection between the gut and stroke.…”