Mechanism and intervention of mucosal immune regulation based on "lung and large intestine being interior-exteriorly related" theory of traditional Chinese medicine / 浙江大学学报·医学版

The "lung and large intestine being interior-exteriorly related" is one of the classical theories in traditional Chinese medicine, which indicates a close correlation between the lung and large intestine in physiology and pathology, and plays a pivotal role in guiding the treatment of the lung and bowel diseases. Modern medicine has revealed some connections between the lung and large intestine in tissue origin and mucosal immunity, and preliminarily illuminated the material basis and possible regulatory mechanism of the theory. Recently, this theory has been applied to guide the treatment of refractory lung and intestine diseases such as COVID-19 and ulcerative colitis and has obtained reliable efficacy. Existing research results show that the anatomical homogeneity of lung and large intestine promotes the correlation between lung-bowel mucosal immunity, and mucosal immunity and migration and homing of innate lymphocytes are one of the physiological and pathological mechanisms for lung and large intestine to share. Under the guidance of this theory, Chinese medicines with heat-clearing and detoxifying or tonic effects are commonly used in the treatment of the lung and intestinal diseases by regulating lung-bowel mucosal immunity and they can be candidate drugs to treat lung/intestinal diseases simultaneously. However, the existing studies on immune regulation are mainly focused on the expression levels of sIgA and cytokines, as well as the changes in the number of immune cells such as innate lymphocytes and B lymphocytes. While the following aspects need further investigation: the airway/intestinal mucous hypersecretion, the functional changes of pulmonary and intestinal mucosal barrier immune cells, the dynamic process of lung/intestinal mucosal immune interaction, the intervention effect of local pulmonary/intestinal microecology, the correlation and biological basis between the heat-clearing and detoxifying effect and the tonic effect, and its regulation of pulmonary/intestinal mucosal immunity. In this paper, we try to analyze the internal relationship between lung and intestine related diseases from the point of view of the common mucosal immune system of lung and intestine, and summarize the characteristics and rules of traditional Chinese medicine compound and its active ingredients, which have regulatory effect on lung and intestine mucosal immune system, so as to further explain the theoretical connotation of "lung and large intestine being interior-exteriorly related" and provide reference for the research and development of drugs for related diseases.

Characteristics of Gastric Microecosystem Composition and Potential Pathogens / 胃肠病学

Gastric microecosystem is composed of all the microbes and the microenvironment in the stomach. A complicated web of interactions, including interactions between Helicobacter pylori and other gastric bacteria, bacteria and bacteria, and bacteria and mucosal immune system is involved in the homeostasis of the gastric microecosystem. Maintaining the balance of microecosystem in the stomach can promote human health, while imbalanced gastric microecosystem can lead to a variety of diseases. The advances in study on characteristics of composition and function of gastric microecosystem and potential pathogens were summarized in this article to provide an insight into the pathogenesis of chronic gastritis.

Expression and Significance of Duodenal Eosinophils in Patients with Functional Dyspepsia / 胃肠病学

Functional dyspepsia( FD)is a group of clinical syndromes presented as upper abdominal pain,epigastric burning sensation,postprandial fullness,satiety and other symptoms,but lack of organic disease causing these symptoms. Eosinophils( EOS)in gastrointestinal tract play an important role in preventing pathogen invasion and maintaining intestinal epithelial homeostasis. In recent years,many studies have shown a significant increase of duodenal EOS in patients with FD. This article reviewed the expression and significance of duodenal EOS in patients with FD.

Irritable Bowel Syndrome in Inflammatory Bowel Disease

Clinicians are frequently challenged to interpret gastrointestinal symptoms in patients with inflammatory disease (IBD). Irritable bowel syndrome (IBS)-like symptoms are common in patients with IBD and the underlying mechanism is likely to be active or occult inflammation of the bowel rather than co-existing IBS. Biopsychosocial construct and mucosal inflammation, stress, alteration of the hypothalamic-pituitary-adrenal axis, and autonomic dysregulation are contributing factors to IBD-IBS. In particular, low-grade inflammation and immune activation are recent topics regarding the underlying mechanism. Some authors have claimed that inflammation could be a common pathophysiologic factor, in which IBS and IBD might represent the two ends of a wide spectrum of chronic inflammatory conditions. Mast cells, enteroendocrine cells, T cells, and B cells are main effector cells in immune responses. Differentiating IBS symptoms from exacerbation of IBD is important, thus preventing the use of excessive IBD medications, with the potential side effects, or narcotics. Medical treatments with anti-diarrheals, anti-spasmodics, anti-depressants, and anxiolytics can be helpful. However, abuse can lead to medication-dependency and bring about side effects. A healthy, balanced lifestyle, including diet and exercise, should be endorsed.

From Cytokines to Toll-Like Receptors and Beyond - Current Knowledge and Future Research Needs in Irritable Bowel Syndrome

The irritable bowel syndrome (IBS) is a complex disorder in which psychosocial, cultural and biological factors, interact. Recent knowledge in the pathophysiology of IBS, seem to combine issues such as a low grade inflammation or immune activation and dysbiosis that can trigger or exacerbate IBS. On the other hand, stress mediated through the hypothalamic-pituitary-adrenal axis can produce motility abnormalities that can modify the microbiota as well, with the subsequent immune activation in the mucosa and stimulation of nerve terminals, generating symptoms of IBS. Also, we speculate that, stress, dysbiosis or an underlying genetic predisposition, may increase the epithelial permeability leading to a contact between pathogens-associated molecular patterns and toll-like receptors in the deeper layers of the gut, developing a host immunity response and IBS generation. We believe that the role of toll-like receptors in IBS and elucidating the communication processes between the immune and the nervous system, warrant future research.

Modulation of protective immunity against herpes simplex virus via mucosal genetic co-transfer of DNA vaccine with beta2-adrenergic agonist

Cholera toxin, which has been frequently used as mucosal adjuvant, leads to an irreversible activation of adenylyl cyclase, thereby accumulating cAMP in target cells. Here, it was assumed that beta2-adrenergic agonist salbutamol may have modulatory functions of immunity induced by DNA vaccine, since beta2-adrenergic agonists induce a temporary cAMP accumulation. To test this assumption, the present study evaluated the modulatory functions of salbutamol co-administered with DNA vaccine expressing gB of herpes simplex virus (HSV) via intranasal (i.n.) route. We found that the i.n. co-administration of salbutamol enhanced gB-specific IgG and IgA responses in both systemic and mucosal tissues, but optimal dosages of co-administered salbutamol were required to induce maximal immune responses. Moreover, the mucosal co-delivery of salbutamol with HSV DNA vaccine induced Th2-biased immunity against HSV antigen, as evidenced by IgG isotypes and Th1/Th2-type cytokine production. The enhanced immune responses caused by co-administration of salbutamol provided effective and rapid responses to HSV mucosal challenge, thereby conferring prolonged survival and reduced inflammation against viral infection. Therefore, these results suggest that salbutamol may be an attractive adjuvant for mucosal genetic transfer of DNA vaccine.

Presença de Candida nas mucosas vaginal e bucal e sua relação com IgA salivar / Relationship between Candida in vaginal and oral mucosae and salivary IgA

OBJETIVO: correlacionar a presença de leveduras do gênero Candida na cavidade bucal e vaginal de mulheres com e sem candidíase vulvovaginal (CVV) com os níveis de IgA secretora (IgAs) presentes na saliva. MÉTODOS: cinqüenta e uma mulheres foram incluídas; 13 apresentaram CVV e 38 formaram o Grupo Controle. De cada paciente, foram coletados 2,0 mL de saliva sem estimulação e secreção vaginal com o auxílio de swab, que foi imerso a seguir em 2,0 mL de solução fisiológica. As amostras foram semeadas em ágar Sabouraud dextrose com cloranfenicol para isolamento e contagem de colônias, e os isolados foram identificadas fenotipicamente. Na saliva de ambos os grupos foi quantificada IgA pela técnica ELISA. RESULTADOS: nas 13 pacientes com diagnóstico clínico e micológico de CVV, a média de unidades formadoras de colônias de Candida por mililitro de secreção vaginal (ufc/mL) foi de 52.723 e 23,8 por cento dos pacientes apresentaram colonização na mucosa bucal com menor quantidade de ufc/mL (6.030). Os níveis de IgAs na saliva foram mais baixos no grupo com CVV (média de densidade: 0,3) quando comparados aos níveis de IgA do Grupo Controle (média de DO: 0,6). Onze pacientes (37 por cento) do Grupo Controle apresentaram colonização por Candida na cavidade bucal, com média de ufc/mL mais baixa quando comparada ao grupo com CVV. O Grupo Controle também apresentou menor quantidade de ufc/mL (1.973) na cavidade vaginal quando comparado com o Grupo CVV (52.942). CONCLUSÕES: os resultados demonstraram que os pacientes com diagnóstico clínico de candidíase vulvovaginal apresentaram maior quantidade de Candida, tanto na cavidade vaginal quanto na bucal, e apresentaram menores níveis de IgA anti-Candida na saliva.

PURPOSE: to correlate the presence of yeast from the Candida genus in the oral and vaginal cavity of women with and without vulvovaginal candidiasis (VVC), with secretor IgA levels (IgAs) present in the saliva. METHODS: among the 51 women included, 13 presented VVC and 38 were the Control Group. An amount of 2.0 mL of saliva without stimulation was collected from each patient, plus vaginal secretion using a swab, which was then immersed in 2.0 mL of physiological solution. Samples were inseminated in Sabouraud dextrose agar with chloramphenicol for isolation and counting of colonies, and the isolated ones, phenotypically identified. IgA has been quantified in the saliva of the women from both groups, by the ELISA technique. RESULTS: in the 13 patients with clinical and mycological diagnosis of VVC, the mean of Candida colony producing unities by milliliter of vaginal secretion (cpu/mL) was 52,723, and 23.8 percent of the patients presented colonization in the oral mucosa with lower amount of cup/mL (6,030). The levels of IgAs in saliva were lower in the group with VVC (DO mean: 0.3), as compared to the IgA levels of the Control Group (DO mean: 0.6). Eleven patients (37 percent) from the Control Group presented Candida colonization in the oral cavity, with a lower cup/mL mean, when compared to the VVC Group. The Control Group also presented a lower amount of cpu/mL (1,973) in the vaginal cavity, when compared to the VVC Group (52,942). CONCLUSIONS: these results have demonstrated that patients with clinical diagnosis of vaginal candidiasis presented a higher amount of Candida both in the vaginal and in the oral cavity, and presented lower levels of anti-Candida IgA in the saliva.