Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke
ABSTRACT Type 2 diabetes (T2D) is an independent risk factor for acute ischemic stroke (AIS), but the underlying mechanisms remain elusive. Because the gut microbiota plays a causal role in both T2D and AIS, we wondered whether gut dysbiosis in T2D aggravates stroke progression. We recruited 35 T2D,...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2021-12-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msystems.01304-21 |
| _version_ | 1798031808682524672 |
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| author | Xiaojiao Chen Qiheng Wu Xuxuan Gao Huidi Wang Jiajia Zhu Genghong Xia Yan He Wei Song Kaiyu Xu |
| author_facet | Xiaojiao Chen Qiheng Wu Xuxuan Gao Huidi Wang Jiajia Zhu Genghong Xia Yan He Wei Song Kaiyu Xu |
| author_sort | Xiaojiao Chen |
| collection | DOAJ |
| description | ABSTRACT Type 2 diabetes (T2D) is an independent risk factor for acute ischemic stroke (AIS), but the underlying mechanisms remain elusive. Because the gut microbiota plays a causal role in both T2D and AIS, we wondered whether gut dysbiosis in T2D aggravates stroke progression. We recruited 35 T2D, 90 AIS, 60 AIS with T2D (AIS_T2D) patients, and 55 healthy controls and found that AIS and T2D had an additive effect on AIS_T2D patient gut dysbiosis by exhibiting the largest difference from the heathy controls. In addition, we found that the degree of gut dysbiosis associated with T2D was positively correlated with the National Institutes of Health Stroke Scale (NIHSS), modified Rankin score (mRS), and Essen stroke risk score in patients with AIS, including AIS and AIS_T2D patients. Compared with mice colonized with gut microbiota from healthy controls poststroke modeling, germfree (GF) mice colonized with gut microbiota from T2D patients showed exacerbated cerebral injury and impaired gut barrier function. Specifically, exacerbated brain injury and gut barrier dysfunction in T2D-treated GF mice were significantly associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. Our study showed that T2D and AIS have an additive effect on AIS_T2D patient gut microbiota dysbiosis. T2D-associated gut microbiota dysbiosis is associated with stroke severity in AIS patients and aggravates stroke progression in mice. IMPORTANCE We demonstrated an additive effect of type 2 diabetes (T2D) and acute ischemic stroke (AIS) on AIS with T2D (AIS_T2D) patient gut microbiota dysbiosis, and gut dysbiosis associated with T2D was positively correlated with stroke severity in AIS patients. Through animal experiments, we found that cerebral injury was exacerbated by fecal microbiota transplantation from T2D patients compared with that from healthy controls, which was associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. This study provided a novel view that links T2D and AIS through gut microbial dysbiosis. |
| first_indexed | 2024-04-11T20:03:32Z |
| format | Article |
| id | doaj.art-6a7c98faeb0848cb94fb8e6d5a267656 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-04-11T20:03:32Z |
| publishDate | 2021-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-6a7c98faeb0848cb94fb8e6d5a2676562022-12-22T04:05:27ZengAmerican Society for MicrobiologymSystems2379-50772021-12-016610.1128/msystems.01304-21Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic StrokeXiaojiao Chen0Qiheng Wu1Xuxuan Gao2Huidi Wang3Jiajia Zhu4Genghong Xia5Yan He6Wei Song7Kaiyu Xu8Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaMicrobiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaMicrobiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaMicrobiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaABSTRACT Type 2 diabetes (T2D) is an independent risk factor for acute ischemic stroke (AIS), but the underlying mechanisms remain elusive. Because the gut microbiota plays a causal role in both T2D and AIS, we wondered whether gut dysbiosis in T2D aggravates stroke progression. We recruited 35 T2D, 90 AIS, 60 AIS with T2D (AIS_T2D) patients, and 55 healthy controls and found that AIS and T2D had an additive effect on AIS_T2D patient gut dysbiosis by exhibiting the largest difference from the heathy controls. In addition, we found that the degree of gut dysbiosis associated with T2D was positively correlated with the National Institutes of Health Stroke Scale (NIHSS), modified Rankin score (mRS), and Essen stroke risk score in patients with AIS, including AIS and AIS_T2D patients. Compared with mice colonized with gut microbiota from healthy controls poststroke modeling, germfree (GF) mice colonized with gut microbiota from T2D patients showed exacerbated cerebral injury and impaired gut barrier function. Specifically, exacerbated brain injury and gut barrier dysfunction in T2D-treated GF mice were significantly associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. Our study showed that T2D and AIS have an additive effect on AIS_T2D patient gut microbiota dysbiosis. T2D-associated gut microbiota dysbiosis is associated with stroke severity in AIS patients and aggravates stroke progression in mice. IMPORTANCE We demonstrated an additive effect of type 2 diabetes (T2D) and acute ischemic stroke (AIS) on AIS with T2D (AIS_T2D) patient gut microbiota dysbiosis, and gut dysbiosis associated with T2D was positively correlated with stroke severity in AIS patients. Through animal experiments, we found that cerebral injury was exacerbated by fecal microbiota transplantation from T2D patients compared with that from healthy controls, which was associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. This study provided a novel view that links T2D and AIS through gut microbial dysbiosis.https://journals.asm.org/doi/10.1128/msystems.01304-21gut microbiotaacute ischemic stroketype 2 diabetes |
| spellingShingle | Xiaojiao Chen Qiheng Wu Xuxuan Gao Huidi Wang Jiajia Zhu Genghong Xia Yan He Wei Song Kaiyu Xu Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke mSystems gut microbiota acute ischemic stroke type 2 diabetes |
| title | Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke |
| title_full | Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke |
| title_fullStr | Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke |
| title_full_unstemmed | Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke |
| title_short | Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke |
| title_sort | gut microbial dysbiosis associated with type 2 diabetes aggravates acute ischemic stroke |
| topic | gut microbiota acute ischemic stroke type 2 diabetes |
| url | https://journals.asm.org/doi/10.1128/msystems.01304-21 |
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