Research on the influence of traditional Chinese medicine therapy on the intestinal flora in obese patients

Pei-Yao Li,Wen-Wen Zhao,Chun-Hua Zhang,Hui-Xin Ding,Ling Wang,Heng Yang,Chun-Guang Yu,

1College of Nursing,Beijing University of Traditional Chinese Medicine,Beijing,China.

Abstract In recent years,the prevalence of obesity has been increasing year by year,leading to a rise in serious complications.The pathogenesis of obesity is complicated in which the intestinal flora plays an important role.Intestinal micro ecology is composed of large and complex intestinal flora that participate in important physiological functions such as metabolism,energy conversion,maintaining intestinal mucosal defense function,and promoting immune system development and maturation and other important physiological functions; furthermore,they are influenced by the host’s genetic background,diet,and other factors.Therefore,intestinal microflora has potential as a new field of drug therapy.At present,it is found that traditional Chinese medicine therapy may prevent and treat obesity by interfering with the intestinal flora,which is expected to become one of the main treatment methods for obese patients.However,its mechanism of action remains unclear.The balance of intestinal flora can be adjusted by acupuncture,massage,and acupoint application.By analyzing the mechanism of obesity caused by intestinal micro ecology and the impact of obesity on the host’s intestinal micro ecological environment,this paper discusses the influence of oral Chinese medicine,acupuncture,massage,acupoint sticking,and other traditional Chinese medicine therapies on the intestinal microflora in obese patients and provides a scientific basis for its clinical application.

Keywords: Intestinal microflora,Obesity,Traditional Chinese medicine,Dysbacteriosis

Introduction

In recent years,the prevalence of obesity has been increasing year by year.The World Obesity Federation emphasizes obesity should be considered a chronic,recurrent,and progressive disease [1].It can lead to glycolipid metabolism disorder,diabetes,hyperlipidemia,hypertension,cardiovascular disease,metabolic syndrome,cancer,and other diseases,seriously threatening human health.The prevalence of obesity in the United States has reached 30% [2].By 2030,there are expected to be 500 million obese people worldwide [3].

The etiology of obesity is complex,and modern medicine believes that obesity is related to the host's genetically determined eating habits and the interaction of intestinal flora [4-5].Among them,the imbalance of intestinal flora is an important factor inducing obesity,which affects the regulation of energy intake and fat storage.Through adjusting diet,exercise,lifestyle,behavior,emotional state,oral medication,probiotics,and weight loss surgery,the body intestinal flora disorder can improve,playing a certain role in weight loss.Metformin can not only improve the body weight and obesity index of high-fat diet-induced obese rats,but also reverse the changes in intestinal flora caused by the high-fat diet in mice,which significantly reduces the diversity of the intestinal flora [6].After weight loss surgery,the intestinal flora changes and metabolic indices were significantly improved [7].

Traditional Chinese medicine (TCM) suggests that adiposity is caused by an improper diet and sugar overload.At present,the theory of treatment from the spleen is generally accepted,and it is believed that obesity is mostly related to damp,phlegm,and deficiency.Therefore,invigorating the spleen and stomach and dislodging the dampness and phlegm are the basic principle of obesity prevention [8,9].TCM plays a unique role in the treatment and prevention of obesity.A previous study found that combining obesity intervention measures with regulation of the intestinal flora can improve and prevent obesity.Therefore,lifestyle intervention combined with TCM therapy has become one of the main treatment methods for obese patients [10].

This study summarizes and analyzes the characteristic therapy of "invigorating the spleen and dampness" in TCM.It includes internal treatment with oral Chinese medicine and external treatment with acupuncture,moxibustion,acupoint sticking,and acupoint embedding.In order to provide a scientific basis for the clinical application of TCM in the treatment of obesity,the role of traditional medicine in the treatment of obesity was discussed from the perspective of affecting the intestinal flora and improving intestinal micro ecology.

The mechanism of intestinal micro ecology causing obesity

Mediation of the development of low-grade inflammation

There are many reasons that obesity could lead to a chronic low-level inflammatory state such as bacterial translocation,increase in lipopolysaccharide (LPS) and free fatty acid levels,and oxidation stress of the endoplasmic reticulum,among others.All of these lead to chronic low-level inflammation in the obese body,which is also an important link between obesity and metabolic disorders [11].In normal physiological conditions,the intestinal epithelium acts as a continuous barrier preventing the invasion of bacteria and toxins.Changes in intestinal flora caused by obesity can damage the gastrointestinal barrier,activating the gastrointestinal immune system and leading to bacterial translocation,thus changing the host metabolism.Studies have shown that intestinal flora regulates intestinal permeability through two factors,glucagon-like peptide-2 and endocannabinoids,of which endocannabinoids are related to inflammation mediated by the intestinal flora [12,13].Endogenous cannabinoids can regulate appetite centers in different regions of the hypothalamus,control food intake and metabolism,and regulate intestinal barrier function,enhancing intestinal permeability,leading to lipopolysaccharide entering the blood and systemic inflammation,thus aggravating obesity [14].

Regulation of intestinal hormone secretion

The increased production of short chain fatty acids (SCFAs) in obese individuals can activate their receptors,Gpr41 and Gpr43,causing increased release of peptide YY.SCFAs inhibit the decomposition of lipids and stimulate the secretion of leptin by adipose tissue.Perryet al.have shown that when eating a high-fat diet,the intestinal flora of animals can produce acetic acid.Acetic acid short-chain fatty acids have the ability to activate the parasympathetic nervous system,which increases hunger hormones and insulin secretion stimulated by glucose,leading to increased appetite,food intake,and body mass; fatty liver; and insulin resistance; as a consequence,obesity,insulin resistance,and metabolic syndrome can develop [15].Therefore,as an energy source for the intestinal flora,SCFAs plays an important role in the generation and development of obesity.

Fasting-induced adipose factor (FIAF)

FIAF regulates the oxidation of fatty acids in the muscle and adipose tissue,inhibits protein lipase activity,and reduces fat storage.An increase in the levels of stachylobacter stachyloides could inhibit adipocyte FIAF,reduce activity of the adenylate-activated protein kinase,and increase triglyceride accumulation.In healthy animals,FIAF can be regulated by the intestinal flora; through inhibition of the expression of FIAF,lipoprotein lipase expression is increased,and lipid deposition is reduced [16].

Role in the metabolism of 5-hydroxytryptamine (5-HT)

5-HT,also known as serotonin,is a neurotransmitter that has especially high contents in the cerebral cortex and synapses and is involved in a variety of physiological functions of regulation.It mainly regulates cardiovascular activity,body temperature,emotional activity,and gastrointestinal function.By regulating the level of 5-HT,it can reduce food intake,control appetite,and increase energy consumption,allowing weight loss to be achieved.Yanoet al.showed that microorganisms produced by fixed bacteria in the intestine are transmitted to endocrine cells in the intestine.Endocrine cells increase the level of Tph1,which regulates 5-HT levels and promotes the synthesis of 5-HT [17].Intestinal flora disorder leads to 5-HT synthesis disorder,increased energy intake,energy imbalance,and obesity.

Regulation of the intestinal bile acid pool

Bile acids are produced by the liver and secreted from the gallbladder to the duodenum.Bile acids activate metabolic signals of the host mainly by binding to nuclear receptors on the cell surface.Bile salt hydrolases,produced by the intestinal flora,dissociate bile acids into bile acid salts as signal molecules; activate Vitamin D,TGR5,and other receptors and cellular signal pathways; and regulate the blood glucose levels and synthesis of fatty acids [18].Following consumption of a high-fat diet,bile acid salt levels increase,destroying the structure of intestinal flora and increasing the firmicutes / bacteroidetes ratio,resulting in obesity.Therefore,intestinal bacteria can regulate the intestinal bile acid pool in multiple ways,affecting the process of fat absorption,oxidation,synthesis,transport,and storage.

Effect of obesity on intestinal micro ecological environment of host

The intestinal flora interacts with the host and environment to influence the host’s biology.At the same time,the host’s dietary behavior,degree of obesity,and lifestyle can exert complex and fine regulation on the intestinal micro ecological environment and intestinal flora.The central nervous system affects the formation and function of adipose cells,and regulates the composition and function of intestinal flora by integrating intestinal flora,endothelial system,adipose tissue,and other relevant signals,and then influences the formation and function of adipose cells through the feeding center and other channels.Mozeset al.fed neonatal mice a high-fat diet and found that the number of lactobacillus increased and bacteroid-like bacteria decreased in the intestinal flora with obesity.The study showed that the diet of neonatal mice affected intestinal function and the composition of the intestinal flora regulating and maintaining the progression of obesity [19].

Obesity alters the body's sensitivity to neuropeptide Y (NPY) and affects intestinal motility.NPY is an appetite-stimulating regulatory factor that plays an important role in the hypothalamus appetite regulatory network and can regulate energy balance.Central NPY inhibits the lipolysis of white adipocytes and heat production of brown adipocytes through antagonistic sympathetic nervous system activity,and can also directly act on peripheral NPY receptors to promote lipogenesis,ultimately leading to obesity [20,21].Therefore,NPY has become a target in the treatment of obesity due to its role in promoting obesity.

In addition,the widespread use of antibiotics and probiotics affects the intestinal micro ecological environment [22].In particular,the abuse of antibiotics in children is more likely to lead to obesity,resulting in changes in the micro ecosystem.However,whether this situation is related to the type and dose of antibiotics requires further study.Probiotics are microorganisms that are beneficial to humans and animals,such as bifidobacteria,lactobacillus,Clostridium tyroate,lactobacillus acidophilus,yeast,etc.By regulating human intestinal flora,the balance of intestinal flora can be maintained.Prebiotics is a dietary supplements that selectively stimulate the growth and activity of bacteria in one or a small number of colonies to have a beneficial effect on the host and thereby improve the host's health.At present,the combination of the two is used in clinical practice to reduce the intake of heat energy,reduce the deposition of fat,and increase the sense of satiety and energy consumption to achieve good therapeutic effects.

The imbalance of intestinal flora in obese pregnant women is likely to lead to the imbalance of intestinal flora in infants.The developmental origin of health and disease indicates the relationship between malnutrition during pregnancy and fetal growth and development as well as the development of long-term chronic diseases after birth.Abnormal intestinal flora and metabolism of obese pregnant women can change the intrauterine nutrition and metabolic environment of the fetus,and increase the risk of diabetes in adulthood,however,the source of microflora of placenta and amniotic fluid during pregnancy,and lack of information about the impact of intestinal flora disorders on maternal and fetal metabolism [23].

The body influences intestinal flora by regulating the synthesis of unsaturated fatty acids.Unsaturated fatty acids can maintain the relative fluidity of cell membrane to ensure the normal physiological function of cells,and can also make cholesterol esterification,decrease the level of blood cholesterol and triglycerides.The human body influences the changes of nutritional status and environmental conditions by regulating the synthesis of unsaturated acids.

Effects of TCM therapy on intestinal micro ecology on obesity

Internal TCM treatments

Liu YFet al.believe that the effective components of TCM are complex in structure and exist in different states after entering the gastrointestinal tract [24].Most of the effective components of TCM are metabolized by specific bacterial groups or enzymes in the body,thus playing a preventive and therapeutic role in the body.Si FGet al.reviewed 200 reports on the diagnosis and treatment of obesity by TCM in the last 30 years [25].The main syndrome types of obesity can be summarized as follows: spleen deficiency and damp weight type,accumulation of damp and heat type,and phlegm-blood stasis syndrome type,among others.The statistical analysis of prescription and TCM showed that common drugs for deficiency were Cangzhu (Rhizoma Atractylodis) and Heshouwu (Radix Polygoni Multiflori); for clearing damp and promoting diuresis,commonly used drugs are Fuling (Poria) and Zexie (Rhizoma Alismatis); for promoting blood circulation to remove blood stasis,commonly used drugs are Danshen (Radix Salviae Miltiorrhizae) and Yujin (Radix Curcumae); common medicines for clearing heat are Juemingzi (Semen Cassiae) and Huanglian (Rhizoma Coptidis); and common drugs for regulating Qi are Chenpi (Pericarpium Citri Reticulatae) and Zhishi (Fructus Aurantii Immaturus).It can be seen from this that the common treatments for obesity are tonifying Qi,resolving dampness,expectorant,tonifying spleen,soothing the liver,harmonizing stomach,and tonifying the kidney.Among them,the most important method is tonifying the spleen and resolving dampness.Li JWet al.observed that taking the Wenyangyiqihuoxue prescription [Paofupian (Radix Aconiti Lateralis Preparata),Renshen (Radix Ginseng),Zhigancao (Radix et Rhizoma),Baizhu (Rhizoma Atractylodis Macrocephalae),Fuling (Poria),Zhike (Fructus Aurantii),Chishao (Radix Paeoniae Rubra),Shanyurou (Fructus Corni),Chaihu (Radix Bupleuri),Guizhi (Radix Bupleuri),Ganjiang (Rhizoma Zingiberis),Danshen (Radix Salviae Miltiorrhizae)] could significantly improve the symptoms of obese patients,effectively reduce insulin resistance,regulate blood lipid metabolism,and adjust the imbalance in intestinal flora [26].Feng Bet al.make administered mice the Jianpitiaogan decoction [Huangqi (Radix Astragali seu Hedysari),Chaihu (Radix Bupleuri),Fuling (Poria),Baishao (Radix Paeoniae Alba),Yimi (Coix Seed),Danshen (Radix Salviae Miltiorrhizae),Peilan (Herba Eupatorii),Juemingzi (Semen Cassiae),Zexie (Rhizoma Alismatis),Shengdahuang (Radix et Rhizoma Rhei),Shanzha (Fructus Crataegi)] decoction orally; they found this decoction could tonify the spleen,regulate the liver,and remove turbidity evil [27].Zhang CHet al.studied Gegenqinlian decoction,a TCM compound.It was found that Gegenqinlian decoction could significantly regulate the structure of the intestinal flora and improve the glucose and lipid metabolism of mice.Furthermore,its antagonistic effect on insulin may be related to the improvement in related inflammatory factors and regulation of intestinal flora structures [28].

Some monomers of TCM also have significant effects of hyperglycemia,improving insulin resistance and regulating the balance of the intestinal flora,with high safety and minor toxic and adverse effects,such as berberine (Berberine hydrochloride),phloridzine,and other monomers of TCM.In addition,relevant experts in the TCM single prescription weight loss mechanism were consulted.Peng XC believes that the effect of cinnamon essential oil on clostridium IV clusters and bacteroides type 2 main flora in the intestinal tract may be one of the mechanisms of cinnamon's action on obesity and diabetes [29].

External treatment of TCM

The treatment of obesity by external therapy of TCM is guided by a holistic view of treatment based on syndrome differentiation.The combination of prevention and treatment can enhance the immune function of the body and improve the functional state of the body.It is widely used in clinical practices,such as acupuncture,moxibustion,massage,acupoint sticking,and acupoint embedding,and has good developmental prospects [30].

Kong YQet al.used cupping combined with auricular point [Liangqiu (ST34),Gongsun (SP4),Zusanli (ST36),Fenglong (ST40),Shangjuxu (ST37),Xiajuxu (ST39),Sanyinjiao (SP6),Yinlingquan (SP9),Guanyuan (CV4),Zhongwan (CV12),Daheng (SP15),Neiguan (PC6),Tianshu (ST25),Pishu (BL20),Shenshu (BL23),etc.] sticking to treat obese individuals and observed changes in the number of escherichia coli and bacteroid-like bacteria in the intestinal flora before and after treatment.They found that cupping therapy combined with auricular point sticking therapy has a better therapeutic effect on simple obesity and has a certain regulating effect on the intestinal flora of obese people [31].Li Pet al.showed that abdominal massage combined with massage [Quchi (LI11),Tianshu (ST25),Yinlingquan (SP9),Fenglong (ST40),Taichong (LR3),Guilai (ST29),Xiawan (CV10),Zhongji (CV3)] in the liver meridian had a significant therapeutic effect on simple obesity [32].Studies have shown that massage combined with acupuncture [main acupoints: Daheng (SP15),Tianshu (ST25),Qihai (CV6),Zhongwan (CV12),Xiawan (CV10),Guanyuan (CV4),Zusanli (ST36),Sanyinjiao (SP6),Fenglong (ST40),etc.] can improve appetite,promote gastrointestinal peristalsis,and regulate intestinal flora [33].Fu JMet al.used acupoint embedding and cupping [Dachangshu (BL25),Tianshu (ST25),Shangjuxu (ST37),etc.] for patients with spleen deficiency and dampness resistance obesity; after treatment,body weight,body fat percentage,BMI,waist circumference,and other indicators were all lower [34].Mao DDet al.conducted meridian scraping on patients [35].The primary selection was to scrape the Shangwan (CV13) acupoint downward to Zhongwan (CV12) and Xiawan (CV10),Qihai (CV6) acupoint downward to scrape the Guanyuan (CV4) and Zhongji (CV3) acupoints; limb scraping of the upper limb hand taiyin lung meridian; and lower limb scraping of the foot yangming stomach meridian and foot taiyin spleen meridian.This was shown to promote metabolism,spleen and dampness,and clear turbidity.External TCM therapy can be used alone or in combination to regulate the intestinal flora,adjusting the dynamic balance of intestinal micro ecology,regulating the spleen and stomach,increasing metabolism,and achieving the effect of weight loss.It is an ecologically friendly and healthy way of achieving weight loss.

Conclusion

In summary,the intestinal microenvironment contains the biggest symbiotic microbial gene pool of the body.The development and progression of obesity has been closely connected with intestinal microecology.The deficiency syndrome of the spleen was related to alteration in the intestinal flora; however,further exploration is necessary in order to find relevant objective species indicators [36].Characteristic TCM therapies including acupuncture,moxibustion,and cupping,have preventive and treatment effects on obesity.By regulating the balance of the intestinal micro ecosystem,it plays a role in maintaining the normal state of the human intestinal flora.