Gut microbiota composition reflects disease progression, severity and outcome, and dysfunctional immune responses in patients with hypertensive intracerebral hemorrhage

Abstract

ObjectiveIn this study, we aimed to explore the alterations in gut microbiota composition and cytokine responses related to disease progression, severity, and outcomes in patients with hypertensive intracerebral hemorrhage (ICH).MethodsFecal microbiota communities of 64 patients with ICH, 46 coronary heart disease controls, and 23 healthy controls were measured by sequencing the V3-V4 region of the 16S ribosomal RNA (16S rRNA) gene. Serum concentrations of a broad spectrum of cytokines were examined by liquid chips and ELISA. Relationships between clinical phenotypes, microbiotas, and cytokine responses were analyzed in the group with ICH and stroke-associated pneumonia (SAP), the major complication of ICH.ResultsIn comparison with the control groups, the gut microbiota of the patients with ICH had increased microbial richness and diversity, an expanded spectrum of facultative anaerobes and opportunistic pathogens, and depletion of anaerobes. Enterococcus enrichment and Prevotella depletion were more significant in the ICH group and were associated with the severity and functional outcome of ICH. Furthermore, Enterococcus enrichment and Prevotella depletion were also noted in the SAP group in contrast to the non-SAP group. Enterococci were also promising factors in the prognosis of ICH. The onset of ICH induced massive, rapid activation of the peripheral immune system. There were 12 cytokines (Eotaxin, GM-CSF, IL-8, IL-9, IL-10, IL-12p70, IL-15, IL-23, IL-1RA, IP-10, RANTES, and TNF-α) changed significantly with prolongation of ICH, and the Th2 responses correlated with the 90-day outcomes. Cytokines TNF-α, IP-10, IL-1RA, IL-8, IL-18, and MIP-1β in SAP group significantly differed from non-SAP group. Among these cytokines, only IP-10 levels decreased in the SAP group. Enterococcus was positively associated with IL-1RA and negatively associated with IP-10, while Prevotella was inversely associated in both the ICH and SAP groups.ConclusionThis study revealed that gut dysbiosis with enriched Enterococcus and depleted Prevotella increased the risk of ICH and subsequently SAP. The altered gut microbiota composition and serum cytokine profiles are potential biomarkers that reflect the inciting physiologic insult/stress involved with ICH.

Gastrointestinal Dysbiosis in Neuro-Critically Ill Patients: A Systematic Review of Case-Control Studies

“…This is opposite to the findings by Luo et al indicating Prevotella is reduced in patients with ICH. In Alzheimer's disease, there was a lower number of Firmicutes and Bifidobacterium and a higher abundance of Bacteroidetes similar to the changes in the brain tumor group in a study by Li et al [12,13].…”

“…[ Out of 774 neurocritical patients, 57.76% were males, followed by 42.24% females. Affected patients and healthy controls with their mean ages were defined in some studies (Table 3) [11][12][13][14][15]. To find the relationship between the intestinal microbiota, cytokines, and clinical severity in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.…”

“…Two studies have documented the effects of cerebrovascular disorders on microbiota dysbiosis, while the other two studies have correlated brain tumors and encephalitis with dysbiosis. The total number of patients in these studies was N = 774 (Table 2) [11][12][13][14][15].…”

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

“…Among them, Verrucomivrobiales (phylum Verrucomicrobiota) was identified to play an important role in distinguishing IPH patients [41]. Additionally, it was found that when the gut microbiota of rats with hemorrhagic transformation was introduced in the intestinal tract of normal rats, the susceptibility of the latter to hemorrhagic transformation increased [42]. In addition, Luo et al reported that the relative abundances of Enterococcus, Parabacteroides, Lachnoclostridium, Acidaminococcus and Streptococcus were higher in ICH patients than in healthy controls, while the relative abundances of Prevotella and Faecalibacterium were lower in ICH patients than in healthy controls.…”

“…Stroke patients had lower levels of SCFAs-producing bacteria and SCFAs. For example, during middle cerebral artery occlusion, mice had lower levels of SCFAs, especially butyrate and valeric acid [42]. The capacity of carbohydrate and amino acid metabolism is increased in the gut bacteria of IPH patients.…”