Integrated Traditional Chinese Medicine Improves Functional Outcome in Acute Ischemic Stroke: From Clinic to Mechanism Exploration With Gut Microbiota

Abstract

As a life-threatening disease, stroke is the leading cause of death and also induces adult disability worldwide. To investigate the efficacy of the integrated traditional Chinese medicine (ITCM) on the therapeutic effects of acute ischemic stroke (AIS) patients, we enrolled 26 patients in the ITCM [Tanhuo decoction (THD) + Western medicine (WM)] group and 23 in the WM group. Thirty healthy people were also included in the healthy control (HC) group. ITCM achieved better functional outcomes than WM, including significant reduction of the phlegm-heat syndrome and neurological impairment, and improvement of ability. These facts were observed in different pretreatment gut enterotypes. In this paper, we collected the stool samples of all participants and analyzed the 16S rRNA sequence data of the gut microbiota. We identified two enterotypes (Type-A and Type-B) of the gut microbial community in AIS samples before treatment. Compared to Type-B, Type-A was characterized by a high proportion of Bacteroides, relatively high diversity, and severe functional damage. In the ITCM treatment group, we observed better clinical efficacy and positive alterations in microbial diversity and beneficial bacterial abundance, and the effect of approaching healthy people’s gut microbiota, regardless of gut enterotypes identified in pretreatment. Furthermore, we detected several gut microbiota as potential therapeutic targets of ITCM treatment by analyzing the correlations between bacterial abundance alterations and functional outcomes, where Dorea with the strongest correlation was known to produce anti-inflammatory metabolite and negatively linked to trimethylamine-N-oxide (TMAO), a biomarker of AIS. This study analyzed clinical and gut microbial data and revealed the possibility of a broad application independent of the enterotypes, as well as the therapeutic targets of the ITCM in treating AIS patients with phlegm-heat syndrome.

The Association between Circulating 25‐Hydroxyvitamin D and Carotid Intima‐Media Thickness Is Mediated by Gut Microbiota and Fecal and Serum Metabolites in Adults

“…[ 34 ] Moreover, the genus Dorea was inversely correlated to atherosclerosis in mice [ 35 ] and the concentration of trimethylamine N‐oxide [TMAO] in acute ischemic stroke patients. [ 36 ] However, Erysipelotrichaceae at the family level were potentially pathogenic bacteria because its some specific taxa were correlated to dyslipidemia [ 37 ] and inflammation. [ 38 ] Therefore, in line with the majority of previous studies, our findings supported that 25(OH)D has the potential to lower the progression of subclinical atherosclerosis via modulating the gut microbiota.…”

Gut microbiota, a hidden protagonist of traditional Chinese medicine for acute ischemic stroke

“…Chinese herbs maintain a healthy gut environment by promoting bowel movement and stimulating bowel movements. For example, Xinglou Chengqi Decoction (XCD) and Tanhuo decoction (THD) are both effective in improving gut dysfunction caused by AIS, reducing symptoms such as bad breath, thick tongue, bloating, dry stools or poor bowel movements ( Chen et al, 2020 ; Wang et al, 2021 ; Guo et al, 2022 ). The gut motility-promoting effect of Chinese herbs may be related to their stimulation of the release of intestinal neurotransmitters.…”

“…Several studies have found that Chinese herbs can upregulate SCFA levels to improve the prognosis of AIS by correcting disorders of the gut microbiota. THD makes SCFA-producing flora such as Blautia, Coprococcus, Streptococcus, Dorea, Streptococcus, Bifidobacterium, and Lactobacillus more accessible to healthy people ( Guo et al, 2022 ). XCD can upregulate Verrucomicrobia and Akkermansia abundance to increase the levels of enteric butyric acid ( Gao et al, 2021 ).…”

“…Lipopolysaccharide (LPS) has been found to promote neuroinflammation in the brain through direct and indirect pathways ( Lukiw et al, 2018 ). THD significantly reduces the number of LPS-producing intestinal flora, such as Mycobacterium avium , in the gut, thereby reducing the level of LPS biosynthesis ( Guo et al, 2022 ). It was found that the reduction in AIS-induced neuronal apoptosis by Chinese herbs may be related to the regulation of the gut microbiota.…”

Effect of Jin three needles combined with Tong Qiao and blood activation Tang on neurological function, coagulation function and serum level in stroke patients

“…Stimulation of specific acupoints along the collaterals may help control the meridian qi (or vital energy), dredge the meridians, and restore the body Yin-Yang balance. [9,10] Jin three needles, a characteristic acupuncture therapy in the Lingnan area, is widely used in clinical practice, particularly for encephalopathy. [11] The pathogenesis of stroke is considered to be an imbalance of Yin and Yang, inversion of Qi and blood, and obstruction of the viscera and qi.…”