Exploring the Associations of Gut Microbiota with Inflammatory and the Early Hematoma Expansion in Intracerebral Hemorrhage: from Change to Potential Therapeutic Objectives

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2025 Feb 18

PMID 39963412

Authors

Haixiao Jiang

Wei Zeng

Fei Zhu

Xiaoli Zhang

Demao Cao

Aijun Peng

Hongsheng Wang

Affiliations

Soon will be listed here.

Abstract

Background: Although a great deal of research has explored the possibility of a systemic inflammatory response and dysbiosis of the gut microbiota after an intracerebral hemorrhage (ICH), the relationships between gut microbiota and blood inflammatory indicators as well as their role in the hematoma expansion following an early-stage mild-to-moderate ICH (emICH) remain unknown. This study analyzes these changes and associations in order to predict and prevent hematoma expansion after emICH.

Methods: The study included 100 participants, with 70 individuals diagnosed with emICH (30 with hematoma expansion and 40 without hematoma expansion, referred to as the HE and NE groups) and 30 healthy controls matched in terms of age and gender (HC). We used 16S rRNA gene sequencing to explore the gut microbial structure and its underlying associations with blood inflammatory parameters in the HE group.

Results: Our findings showed a significant decrease in the diversity and even distribution of microorganisms in the HE group when compared to the HC and NE groups. The composition of the gut microbiota experienced notable alterations in the emICH group, especially in HE. These changes included a rise in the number of gram-negative pro-inflammatory bacteria and a decline in the level of probiotics. Furthermore, we observed strong positive connections between bacteria enriched in the HE group and levels of systemic inflammation. Several microbial biomarkers (e.g. , and ) were revealed in disparateiating HE from HC and NE. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) exposed disturbances in essential physiological pathways, especially those related to inflammation (such as the Toll-like receptor signaling pathway), in the HE group.

Conclusions: Our exploration indicated that individuals with emICH, especially those with HE, demonstrate notably different host-microbe interactions when compared to healthy individuals. We deduced that emICH could rapidly trigger the dysbiosis of intestinal flora, and the disturbed microbiota could, in turn, exacerbate inflammatory response and increase the risk of hematoma expansion. Our comprehensive research revealed the potential of intestinal flora as a potent diagnostic tool, emphasizing its significance as a preventive target for HE.

References

Streit F, Prandovszky E, Send T, Zillich L, Frank J, Sabunciyan S . Microbiome profiles are associated with cognitive functioning in 45-month-old children. Brain Behav Immun. 2021; 98:151-160. DOI: 10.1016/j.bbi.2021.08.001. View

Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C . Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2016; 49:60-68. DOI: 10.1016/j.neurobiolaging.2016.08.019. View

Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M . KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2020; 49(D1):D545-D551. PMC: 7779016. DOI: 10.1093/nar/gkaa970. View

Li M, Su J, Wu J, Zhao D, Huang M, Lu Y . The Prebiotic Activity of a Novel Polysaccharide Extracted from by Fecal Fermentation . Foods. 2023; 12(24). PMC: 10743195. DOI: 10.3390/foods12244406. View

Xu K, Gao X, Xia G, Chen M, Zeng N, Wang S . Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn. Gut. 2021; . DOI: 10.1136/gutjnl-2020-323263. View

Rognes T, Flouri T, Nichols B, Quince C, Mahe F . VSEARCH: a versatile open source tool for metagenomics. PeerJ. 2016; 4:e2584. PMC: 5075697. DOI: 10.7717/peerj.2584. View

Di Lorenzo F, Duda K, Lanzetta R, Silipo A, De Castro C, Molinaro A . A Journey from Structure to Function of Bacterial Lipopolysaccharides. Chem Rev. 2021; 122(20):15767-15821. DOI: 10.1021/acs.chemrev.0c01321. View

Fonseca S, Costa F, Seabra M, Dias R, Soares A, Dias C . Systemic inflammation status at admission affects the outcome of intracerebral hemorrhage by increasing perihematomal edema but not the hematoma growth. Acta Neurol Belg. 2020; 121(3):649-659. DOI: 10.1007/s13760-019-01269-2. View

Loan J, Salman R, McColl B, Hardingham G . Activation of Nrf2 to Optimise Immune Responses to Intracerebral Haemorrhage. Biomolecules. 2022; 12(10). PMC: 9599325. DOI: 10.3390/biom12101438. View

10.

Lian Z, Xu Y, Wang C, Chen Y, Yuan L, Liu Z . Gut microbiota-derived melatonin from Puerariae Lobatae Radix-resistant starch supplementation attenuates ischemic stroke injury via a positive microbial co-occurrence pattern. Pharmacol Res. 2023; 190:106714. DOI: 10.1016/j.phrs.2023.106714. View

11.

Shi Y, Zhang L, Do K, Peterson C, Jenq R . aPCoA: covariate adjusted principal coordinates analysis. Bioinformatics. 2020; 36(13):4099-4101. PMC: 7332564. DOI: 10.1093/bioinformatics/btaa276. View

12.

Li H, Xie J, Guo X, Yang G, Cai B, Liu J . spp. and their metabolite lactate protect against acute pancreatitis via inhibition of pancreatic and systemic inflammatory responses. Gut Microbes. 2022; 14(1):2127456. PMC: 9542615. DOI: 10.1080/19490976.2022.2127456. View

13.

Yi Y, Shen L, Shi W, Xia F, Zhang H, Wang Y . Gut Microbiome Components Predict Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Prospective, Longitudinal Study. Clin Cancer Res. 2020; 27(5):1329-1340. DOI: 10.1158/1078-0432.CCR-20-3445. View

14.

Erawijantari P, Mizutani S, Shiroma H, Shiba S, Nakajima T, Sakamoto T . Influence of gastrectomy for gastric cancer treatment on faecal microbiome and metabolome profiles. Gut. 2020; 69(8):1404-1415. PMC: 7398469. DOI: 10.1136/gutjnl-2019-319188. View

15.

Li L, Poon M, Samarasekera N, Perry L, Moullaali T, Rodrigues M . Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021; 20(6):437-447. PMC: 8134058. DOI: 10.1016/S1474-4422(21)00075-2. View

16.

Lusk J, Covington A, Liu L, Weikel D, Li Y, Sekar P . Hyperglycemia, Ischemic Lesions, and Functional Outcomes After Intracerebral Hemorrhage. J Am Heart Assoc. 2023; 12(13):e028632. PMC: 10356065. DOI: 10.1161/JAHA.122.028632. View

17.

Hall A, Yassour M, Sauk J, Garner A, Jiang X, Arthur T . A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med. 2017; 9(1):103. PMC: 5704459. DOI: 10.1186/s13073-017-0490-5. View

18.

Liu F, Li J, Guan Y, Lou Y, Chen H, Xu M . Dysbiosis of the Gut Microbiome is associated with Tumor Biomarkers in Lung Cancer. Int J Biol Sci. 2019; 15(11):2381-2392. PMC: 6775324. DOI: 10.7150/ijbs.35980. View

19.

Wang T, Town T, Alexopoulou L, Anderson J, Fikrig E, Flavell R . Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med. 2004; 10(12):1366-73. DOI: 10.1038/nm1140. View

20.

Yang Y, Misra B, Liang L, Bi D, Weng W, Wu W . Integrated microbiome and metabolome analysis reveals a novel interplay between commensal bacteria and metabolites in colorectal cancer. Theranostics. 2019; 9(14):4101-4114. PMC: 6592169. DOI: 10.7150/thno.35186. View