Gut microbiota and differential genes-maintained homeostasis is key to maintaining health of individuals with Yang-deficiency constitution

doi:10.19852/j.cnki.jtcm.20211012.001

Journal of Traditional Chinese Medicine ›› 2022, Vol. 42 ›› Issue (1): 96-101.DOI: 10.19852/j.cnki.jtcm.20211012.001

• Research Articles • Previous Articles Next Articles

Gut microbiota and differential genes-maintained homeostasis is key to maintaining health of individuals with Yang-deficiency constitution

Huixiang ZHANG¹, Limei WANG², Jipeng GUO⁵, Jiai WANG⁶, Qianqian ZHANG⁷, Yutao WANG⁷, Xun LIU⁷, Lihuan ZHANG², Lanlan SHI⁸, Hongxiang WU⁴(), Xue CAO³()

1 Institute of Neuroscience, Basic Medical College, Kunming Medical University, Kunming 650500, China
2 Department of Laboratory Animal Science, Kunming Medical University, Kunming 650500, China
3 Department of Laboratory Animal Science, Kunming Medical University, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650500, China
4 Faculty of Rehabilitation Medicine, Kunming Medical University, Kunming 650500, China
5 School of Electrical and Information Technology, Yunnan Minzu University, Kunming 650500, China
6 School of Medicine, Kunming University, Kunming 650214, China
7 Basic Medical College, Kunming Medical University, Kunming 650500, China
8 Department of Anatomy, Histology and Embryology, Basic Medical College, Kunming Medical University, Kunming 650500, China

Received:2021-02-01 Accepted:2021-05-08 Online:2022-02-15 Published:2021-12-12
Contact: Hongxiang WU,Xue CAO
About author:Associate Prof. WU Hongxiang, Kunming Medical University, Kunming 650500, China. w.hq11111@163.com
Associate Prof. CAO Xue, Kunming Medical University, Kunming 650500, China. dir1865@163.com;
Supported by:
Applied Basic Research Foundation of Yunnan Province(202101AY070001-050);Applied Basic Research Foundation of Yunnan Province(2019FE001-026);Open Foundation of State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University(2019KF003);National Natural Science Foundation of China(81860255);National Natural Science Foundation of China(81760869);Scientific Research Foundation of Yunnan Provincial Department of Education(2018JS159)

Abstract

Abstract:

OBJECTIVE: Yang-deficiency constitution (YADC) is a common unbalanced constitution that predisposes individuals to certain diseases. However, not all people with YADC manifest develop diseases. This calls for delineation of the underlying molecular mechanisms. Previous studies suggested that the gut microbiota and gene differential expression should be considered.

METHODS: In the present study, we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution (BC) counterparts, based on 16S rRNA gene sequence analysis. Furthermore, YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis, functional clustering and pathway enrichment analyses.

RESULTS: The levels of harmful gut microbiota (Prevotellaceae, LDA score > 4.0, P = 0.0141) and beneficial gut microbiota (Ruminococcaceae, LDA score > 4.0, P = 0.0025, Faecalibacterium, LDA score > 4.0, P = 0.0484) were both elevated in healthy YADC individuals. Also, we found that the specific metabolic pathway with 2, 6-Dichloro-p-hydroquinone 1, 2-Dioxygenase (PcpA) as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon substances.

CONCLUSIONS: Both beneficial and harmful factors had been detected in healthy YADC individuals, functionally, they may have triggered homeostasis to maintain the health of individuals with YADC. The homeostasis may be maintained by beneficial and harmful factors from gut flora and genes. Future studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.

Key words: Yang deficiency, physical constitution theory, health promotion, gastrointestinal microbiome, genes, hydrocarbons, aromatic, homeostasis

Huixiang ZHANG, Limei WANG, Jipeng GUO, Jiai WANG, Qianqian ZHANG, Yutao WANG, Xun LIU, Lihuan ZHANG, Lanlan SHI, Hongxiang WU, Xue CAO. Gut microbiota and differential genes-maintained homeostasis is key to maintaining health of individuals with Yang-deficiency constitution[J]. Journal of Traditional Chinese Medicine, 2022, 42(1): 96-101.

Figures/Tables 3

Figure 1 The intestinal flora and genes related to YADC are different from those of BC, which may be related to the disease susceptibility of YADC A: principal coordinate analysis (PCoA) of bacterial communities based on weighted UniFrac distances between all samples; B, C: the most differential abundant bacterial taxa between YADC and BC identified by LEfSe method (B) and MetaStats analysis (C). aP < 0.05, bP < 0.01; D: gene function comparison of gut microbiota between YADC and BC; E: metabolic pathways comparison of gut microbiota between YADC and BC. The thin and thick red lines represent the relative abundance of KOs was higher in YADC and BC (P < 0.05), respectively. The yellow lines present KOs especially presenting in YADC. The yellow line shown by the blue circle on the left is the special metabolic pathway, centered around PcpA in YADC, and the right circle is an enlarged view; F: the catabolic pathway in which PcpA participated in the degradation of pentachlorophenol. The red * indicates that the substance has a toxic effect, and the reaction in the red box is the step catalysed by PcpA; G: intersection analysis of differentially expressed genes. YADC: Yang-deficiency constitution; BC: balanced constitution; PCP: pentachloropheno; PcpB: pentachlorophenol hydroxylase; TCBQ: tetrachlorobenzoquinone PcpD TCBQ reductase; TCHQ: tetrachlorohydroquinone; PcpC: TCHQ dehalogenase; 2, 6-DCHQ: 2, 6-dichlorohydroquinone; PcpA: 2, 6-DCHQ dioxygenase; GSH: glutathione, PcpE: maleylacetate reductase.

Table 1 Partial differential gene enrichment pathways

Category		Term	P value
Partial enrichment pathways	MF	GO: 0004364~glutathione transferase activity	< 0.05
	MF	GO: 0050840~extracellular matrix binding	< 0.05
	KEGG	hsa05323: rheumatoid arthritis	< 0.05
	KEGG	hsa04668: TNF signaling pathway	< 0.05
	BP	GO: 0045892~negative regulation of transcription, DNA-templated	< 0.01
	BP	GO: 0060087~relaxation of vascular smooth muscle	< 0.01
Pathways related to microorganisms	KEGG	hsa05134: legionellosis	< 0.05
	KEGG	hsa05164: influenza A	< 0.05
	BP	GO: 0019732~antifungal humoral response	< 0.05
	BP	GO: 0044130~negative regulation of growth of symbiont in host	< 0.05

Table 2 Variation in the relative abundance of differential gut microbiota in diseases to which YADC are susceptibility

Differential flora	Function	The changing trend	Reference
f_Ruminococcaceae↑	Benefit	Heart failure ↓, gastric cancer↓, coronary artery disease↓	26, 30, 31
g_Faecalibacterium↑	Benefit	Heart failure↓, gastric cancer↓, coronary artery disease↓, type 2 diabetes↓,	26, 30-32
f_Prevotellaceae↑	Harmful	Gastric cancer↑, lung cancer↑, breast cancer↑	26, 33, 34

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