Gut Microbiota‐Related Effects of Tanhuo Decoction in Acute Ischemic Stroke

Abstract

Acute ischemic stroke (AIS) is a major cause of acquired adult disability and death. Our previous studies proved the efficacy and effectiveness of Tanhuo decoction (THD) on AIS. However, the therapeutic mechanism remains unclear. We recruited 49 AIS patients and 30 healthy people to explore the effects of THD+basic treatment on the poststroke gut microbiota of AIS patients using 16S rRNA sequencing, in which 23 patients received basic treatment (control group) and 26 patients received THD+basic treatment (THD group). By comparing the data before and after treatments, we found the THD group acquired better outcome than the control group on both clinical outcome indices and the characteristics of gut microbiota. In addition to the mediation on short-chain fatty acid- (SCFA-) producing bacteria in two groups, treatment in the THD group significantly decreased the lipopolysaccharide- (LPS-) producing bacteria to reduce LPS biosynthesis. Besides, the complexity of the cooccurrence of gut microbiota and the competition among LPS-producing bacteria and opportunistic pathogenetic bacteria were enhanced in the THD group. Treatment in the THD group also exhibited the potential in decreasing genes on the biosynthesis of trimethylamine (TMA), the precursor of Trimethylamine N-oxide (TMAO), and increasing genes on the degradation of TMA, especially increasing trimethylamine-corrinoid protein Co-methyltransferase (mttB) which catabolizes TMA to methane. These results hinted that THD+basic treatment might exert its efficacy by mediating the gut microbiota and microbial metabolites, including LPS and TMAO that aggravate the sterile inflammation and platelet aggregation. Moreover, the well-fitting regression model results in predicting the clinical outcome with the alteration of gut microbiota proved gut microbiota as a potential indicator of AIS and provided evidence of the communication between the gut and brain of AIS patients.

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

“…In order to solve phlegm-heat syndrome, we created a Tanhuo decoction (THD) with the effects of clearing heat, removing phlegm, and eliminating turbid. The decoction is combined with WM treatment to improve both the TCM syndromes and neurological deficits (Guo et al, 2021). We also found that THD has the effects of antiinflammation, antiplatelet aggregation, and reducing fibrinogen (Song et al, 2019b).…”

“…To illustrate the underlying mechanisms of the ITCM treatment at the microbial level, we analyzed the gut microbiota data before and after treatment. Our previous study observed a better improvement of several beneficial bacteria after ITCM treatment than after WM treatment (Guo et al, 2021). In the current study, we evaluated the effects of ITCM in different gut enterotypes.…”

“…The company performed quality control of the herbs and determined the main chemicals via high-performance liquid chromatography. The decoction was prepared by Xuanwu Hospital Capital Medical University according to the standard production process (Guo et al, 2021). Patients in the ITCM group orally took one dose decoction a day, a half for the morning and a half for the evening, for 7 days.…”

“…We then annotated the ASVs using a naive Bayesian classifier method with 99% identity Greengenes rRNA database (version 13.8.99) (DeSantis et al, 2006). After that, the abundance matrices at the levels of phylum, class, order, family, and genus were created for each sample (Wang et al, 2019;Xu et al, 2020;Guo et al, 2021). The composition of gut microbiota of patients was typed into different enterotypes using the "DMM" R package (version 1.32.0) (Holmes et al, 2012).…”

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention

“…Calorie restriction also can promote ischemic stroke rehabilitation via enriching the abundance of Bifidobacterium (73). Tanhuo decoction also promoted poststroke recovery by decreasing the biosynthesis of TMA, the precursor of TMAO, and increasing the expression of trimethylamine-corrinoid protein Co-methyltransferase (mttB), which catabolizes TMA to methane (69). Additionally, Lactulose supplementation was shown to significantly improve the functional outcome of stroke, which is possibly mediated by repairing intestinal barrier injury and improving gut microbiota dysbiosis following stroke (75).…”