Inter-Organ Relationships among Gut, Lung and Skin beyond the Pathogenesis of Allergies: Relevance to the Zang-Fu Theory in Chinese Medicine

Research on allergy has recently uncovered an apparent co-occurrence of allergies in skin and the lungs, a phenomenon that has been coined “atopic march”. A positive correlation has been found between gut microbiota at birth and the development of asthma and skin eczema later in life. Chinese medicine has long described a functional relationship between the large intestine and the lungs, and between the lungs and skin. In this short article, we examined the evidence in support of these inter-organ physiological/pathological relationships. In addition to the clinical observation of the relationship between the composition of gut microbiota at birth and the development of asthma later in childhood, gut microorganisms have also been shown to exert a protective effect on bacteria-induced pneumonia in experimental animals. Genetic predisposition was also found to play an important role in the co-existence of certain diseases of lung and skin. Despite the fact that the mechanism(s) underlying the connection of immune systems between two organs (such as the large intestine and the lungs) is still not clearly understood, it is the first time to correlate the relationship among gut, lung and skin based on recent clinical studies in relation to the Zang-Fu Theory in Chinese medicine. Future investigation of the gut-lung and lung-skin axes in terms of physiological/pathological relationships may help to provide a greater understanding of the pathogenesis of allergies, possibly establishing relevance to the Zang-Fu Theory in Chinese medicine.

Network Biological Modeling:A Novel Approach to Interpret the Traditional Chinese Medicine Theory of Exterior-Interior Correlation Between the Lung and Large Intestine

Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.

The influence of intestine-based treatment using Xuan Bai Cheng Qi Tang on the concentration of trace elements in the main organs of COPD rats

Objective:To test two theories from traditional Chinese medicine:'exterior -interior relationship between the lung and large intestine' and 'treating from the intestine principle for lung disorders'.The influence of intestine-based treatment using Xuan Bai Cheng Qi Tang (XBCQT) on the concentration of three trace elements-copper (Cu),zinc (Zn),and manganese (Mn)-was observed in the tissues of the lung,small intestine,large intestine,and stomach of rats suffering from chronic obstructive pulmonary disease (COPD).Methods:Thirty-five male Wistar rats were divided randomly and equally into five groups:control;model;Fei treatment (A);Chang treatment (B);and Fei-Chang treatment (C).A rat model of COPD was prepared by tracheal injection of lipopolysaccharide plus exposure to cigarette smoke.Treatments with medicinal herbs started day-22 of administration and exposure to cigarette smoke for 7 days.The control group and model group were administered physiologic (0.9%) saline solution via the stomach.After 7 days of intervention,the tissues of the lung,small intestine,large intestine,and stomach were removed.Inductively coupled plasma-atomic emission spectroscopy was used to detect the levels of Cu,Zn,and Mn in those tissues.Results:Compared with the control group,the Cu concentration in the tissues of the small intestine,large intestine,and stomach increased significantly in the model group (P <.05);the Mn concentration in the tissues of the lung,large intestine,and stomach increased significantly in the model group (P <.05);the Zn concentration in the tissues of the lung and large intestine decreased significantly in the model group (P <.05).In comparison of the model group:the Cu concentration in the tissues of the lung and large intestine decreased significantly in the B group (P <.05);the Mn concentration in the tissues of the lung,small intestine,and large intestine decreased significantly in the B group (P <.05);the Zn concentration in the tissues of the lung,small intestine,and large intestine increased significantly in the B group (P <.05).For the A group versus C group comparison,the Zn concentration in the tissues of the small intestine and stomach increased significantly in the latter (P <.05).Conclusion:This study showed that 'treating from the intestine' using Xuan Bai Cheng Qi Tang and its modified formulae can regulate the concentration of trace elements in the main organs of COPD rats.This may be one of the mechanisms for intestine-based treatment for COPD.

Infrared Thermal Imaging-Based Research on the Intermediate Structures of the Lung and Large Intestine Exterior-Interior Relationship in Asthma Patients

Objective: By observing body surface temperature variation of the intermediate structures of the Lung(Fei) and Large Intestine(Dachang) exterior-interior relationship in asthmatic patients, to investigate the pathological response on the pathway of channels and to substantiate the objective existence of the intermediary structures. Methods: The study included 60 subjects meeting the bronchial asthma inclusion criteria(experimental group) and 60 healthy subjects(normal control group). ATIR-M301 infrared thermal imaging device was used for detecting body surface temperature of the subjects and collecting the infrared thermal images. The temperature values of the intermediate structures of Lung and Large Intestine exterior-interior relationship [throat, Quepen, elbow, nose, Lieque(LU 7), Pianli(LI 6)], control areas(0.2 cm lateral to the above structures) and Yintang(EX-HN 3) were measured on the infrared thermal image by infrared imaging system. Then, the above temperature values were compared and analyzed within and between two groups. Results: There were insignificant differences between the temperature on the left and right sides of the intermediate structures(Quepen, elbow, LU 7, LI 6) in normal control group(P>0.05). Except for that of Quepen, there were insignificant differences between the temperature of the intermediate structures and their corresponding control areas in normal control group(P>0.05). In the experimental group, the temperature on the left and right sides of the intermediate structures(Quepen, elbow, LU 7, LI 6) showed statistically significant differences(P<0.05 or P<0.01); the temperature difference between intermediate structure(throat, Quepen, elbow, nose, LI 6) and their respective control areas were also significant(P<0.05 or P<0.01). The temperature of the intermediate structures(throat, Quepen, elbow, LU7, LI 6) between the experimental group and normal control group showed significant differences(P<0.05 or P<0.01). Conclusions: This study is an initial step to validate the objective existence of Lung and Large Intestine exterior-interior relationship intermediate structures, as described in the Chinese classical medical literatures, through the functional imaging angle. The intermediate structures are the pathological reaction areas of the bronchial asthmatic patients.

The Association between Pulmonary Function Impairment and Colon Inflammation in Ulcerative Colitis Patients： A Scientific Basis for Exterior-Interior Correlation between Lung and Large Intestine

Objective： To investigate the involvement of pulmonary function impairment in ulcerative colitis（UC）, and explore a scientific basis for the Chinese medicine（CM） theory of exterior-interior correlation between Lung（Fei） and Large intestine（Dachang）. Methods： Totally 120 patients with a diagnosis of UC were recruited and the demographics, clinical data, and blood samples were collected. C-reactive protein（CRP） and erythrocyte sedimentation rate（ESR） concentrations were measured. Every patient accepted pulmonary function test and took chest radiograph（CXR）. Results： Pulmonary function abnormalities were present in 72 of 120 patients. The median（interquartile range） vital capacity（VC）, forced vital capacity（FVC）, forced expiratory volume in 1 s（FEV_1）, carbon monoxide diffusion capacity（DL_∞） of lung, total lung capacity（TLC） and functional residual volume（FRV） were decreased in distal UC and pancolitis compared with ulcerative prochitis（P〈0.0005）. Male patients had increased VC, FEV_1/FVC, and residual volume（RV）/TLC compared with female（P〈0.0005）, but decreased DLCO and carbon monoxide iffusion capacity（KCO） of lung/alveolar ventilation（P〈0.0005）. Age was strongly correlated with RV（Spearman rank correlation coefficient（rs）=–0.57, P〈0.0001）, and RV/TLC（rs=0.48, P〈0.0001）. Age was also correlated with FEV_1/FVC（rs=–0.29, P=0.001）, forced expiratory flow in 75% vital capacity（FEF75%, rs=–0.20, P=0.03）, DLCO（rs=–0.21, P=0.02）, TLC（rs=–0.25, P=0.006）, and FRV（rs=–0.28, P=0.002）. The course of disease was correlated with FEF75%（rs=–0.18, P=0.049） and KCO（rs=–0.19, P=0.036）. Chest radiograph abnormalities were presented in 38 of 120. Pulmonary symptoms were presented in 10 of 120. Other extraintestinal complications were presented in 21 of 120. Conclusions： Pulmonary function impairment was more frequently than other extraintestinal complications in UC patients, which may be affected by sex, age, extent and course of disease. These results may be a scientific basis for the theory of exterior-interior correlation between Lung and Large intestine.

The TCM Pattern of the Six-Zang and Six-Fu Organs Can Be Simplified into the Pattern of Five-Zang and One-Fu Organs

Objective: To simplify the TCM pattern of the zang-fu organs. Methods: A database of zang-fu syndromes was established. The relationship between the zang-fu syndromes was analyzed by means of frequency analysis, association rule, and ф-coefficient correlation. Results: The six zang-fu organs of the heart, liver, spleen, lung, kidney, and stomach prove to be the main components of the zang-fu pattern. The large intestine, small intestine, gallbladder, bladder, triple energizer, and pericardium have strong association and positive correlation with the above-mentioned six zang-fu organs, and their clinical symptoms can all be included into the symptoms of these six zang-fu organs. Conclusion: The traditional TCM pattern of six-zang and six-fu can be simplified into five-zang and one-fu.