According to Chinese medicine theory, visceral organs can be divided into 2 categories, namely, Zang and Fu, wherein each Zang organ has its corresponding Fu organ(s). The Lung is such a Zang organ, and its Fu organ is the Large Intestine. The Zang-Fu Theory states that the Lung can be infiltrated by “evil” (i.e., pathogens) entering from the Large Intestine [7] .

In modern medicine, it has been observed that some lung diseases are pathologically related to the gut. Chronic lung disorders such as asthma and cystic fibrosis have been shown to exhibit manifestations in the gastrointestinal tract, namely, shifts in the gut microbiota composition [6] . A strong correlation was found between childhood asthma and low diversity of gut microbiota during infancy. It should be noted that the microbiota diversity is restored as early as 12 months after birth, long before asthmatic symptoms arise, suggesting the existence of a time-frame window for the pathogenesis of asthma [3] . A similar correlation was observed experimentally in mice; following a reduction in the num- ber and diversity of gut microorganisms by the administration of antibiotics at 3 weeks of age, adult mice showed exacerbated experimental allergic airway inflammation upon aero-allergen exposure [8] . Similarly, for children with cystic fibrosis, which is a genetic disorder that mainly affects the lungs, there is a large difference between their gut microbiota as compared to healthy children of the same age, with diminished levels of certain bacteria in affected children [9] .

The connection between gut microbiota and lung health is further emphasized in a study by Schuijt et al. [10] , in which mice were depleted of gut microbiota, and then infected with Streptococcus pneumoniae. A group of mice were then given a fecal microbiota transplant and compared with control mice in terms of parameters of inflammation and alveolar macrophage whole-genome responses. Results showed that fecal microbiota transplantation protected microbiota-dep- leted mice against pneumonia, as assessed by parameters relating to bacterial dissemination, inflammation, organ damage and mortality. Metabolic pathways within alveolar macrophages were significantly affected by the absence of gut microbiota, with reduced cellular responses to certain metabolites, such as lipoteichoic acid and lipopoly saccharide. Macrophages from microbiota-depleted mice also showed a reduced ability to kill bacteria (Streptococcus pneumoniae) by phagocytosis.

Taken together, these experimental results suggest a pathological inter-rela- tionship between gut microbiota and lung diseases. It is thought that the gut affects the lung’s immune system, but the mechanism is not well understood. A paper by Trompette et al. [11] found that the fatty acid moiety produced in the metabolism of dietary fibre, by gut microbiota, influences the severity of allergic inflammation in the airways. More research is still needed to further explore the mechanism underlying the effect of gut microbiota on pulmonary function and susceptibility to respiratory diseases.

The Zang-Fu Theory proposes that skin is functionally linked to the Lung, with the Lung playing a role in controlling the “gaps” or pores on the skin, thereby regulating sweating and body temperature, as well as the skin’s immune system. According to Chinese medicine theory, if a patient manifests symptoms reflecting poor respiratory function, or insufficient Lung Qi (which refers to the physiological functioning of the Lung), foreign “evil” can easily invade the body by passing through it souter surface. If Lung Qi is at an optimal level, then the skin is glossy and the complexion shiny. In this connection, Houttuynia cordata Thunb is a commonly used herb for treating both pneumonia and skin eczema [12] .

In modern medicine, an association between allergic diseases of the lungs and airways with those of the skin has been observed (see “atopic march”). However, this pathological inter-relationship can extend beyond allergies, i.e., including non-allergic diseases of these two organs.

However, it is important to first note that many pulmonary diseases, although sometimes exhibiting dermatological manifestations [13] [14] , many of them also show symptoms elsewhere in the body. For example, lung cancer has a 1% to 12% likelihood of developing skin metastases, but the neoplasia may also invade other organs in the body [13] . Similarly, Mycobacterium tuberculosis can infect organs other than the lungs, including the skin, and cause lesions [14] , displaying the possibility of relation between skin and lungs. But again, the tuberculosis bacterium can also invade other organs. Using only dermatological manifestations of non-allergic pulmonary diseases which have no high co-occurrence, especially in the case where it is not an exclusive manifestation, is not enough to form a convincing argument for a unique connection between skin and lungs.

One example of strong co-occurrence of lung and skin problems is high levels of airborne pollutants and lower skin health. Smoking and air pollution have long been known to affect the condition of the skin―for example, causing premature wrinkles, as evidenced by epidemiological studies. Huls et al. reported an association between nitrogen dioxide (NO₂) levels in the environment and the geometric mean number of cheek lentigines, or pigmented spots, commonly known as liver spots [15] . This association was observed in two different populations (Germany and China) in regions with similar UV exposures, and with individuals over 50 years of age [15] . In this regard, NO₂ exposure has been known to impair lung function and increase the risk of lung cancer [16] . However, it should be noted that the increase in the incidence of cheek lentigines was fairly small when estimated on the basis of a per unit increase in NO₂. Further studies are required to confirm these findings [17] .

In another study, Vierkotter et al. (2010) showed that cigarette smoking and ambient soot levels promoted prominently visible signs of skin aging, including pigment spots and wrinkles [18] . With this finding, they demonstrated, for the first time, that airborne particulate matter was a factor in causing extrinsic skin aging [18] .

In the foregoing discussion, it has been shown that extrinsic factors, such as air pollutants and cigarette smoke, are associated with both skin wrinkling and a decline in lung function [18] . In this regard, a study from Vierkotter et al. showed that elderly women carrying certain matrix metalloproteinase (MMP) promotor variants exhibited a higher susceptibility to skin wrinkling and decreased lung function (as assessed by the ratio of forced expiratory volume to forced volume capacity) [19] . As such, not only did they demonstrate an association between skin wrinkling and obstruction of lung function, but also a common genetic predisposition to skin and lung disorders. MMP are a group of extracellular matrix (ECM) degrading enzymes. It has been suggested that the association of smoking with lung dysfunction and skin aging is due to such MMP-induced structural changes in ECM [19] . The specific MMP promoter variants identified are designated MMP-1 and MMP-3. Interestingly, MMP-1 promoter polymorphism also appear to increase susceptibility to colorectal cancer, according to two other studies, again implicating a possible linkage between lung and gut health [20] [21] .

In research of allergic diseases, genetic and environmental factors have both been noted to strongly influence the development of atopic march [1] . The common genetic predisposition to lung and skin aging above suggests an association between lung and skin function that extends beyond those of allergic diseases. One study followed a group of infants who had acute severe bronchiolitis, and found that 50% of them developed dry skin or eczema within 12 months post-recovery from the bronchiolitis. [22] . Another study found that babies suffering from atopic dermatitis in their first 2 years of life had an increased risk of not only asthma, but other respiratory system-related diseases, as assessed by the incidence of acute otitis media (a middle ear infection), pneumonia and the use of antibiotics [23] . The association between atopic dermatitis and respiratory infections prevailed even after stratification for asthma.

The gut-skin relationship, which is not the main scope in this review, has been reported recently. In brief, O’Neill et al. have proposed a gut-skin relationship in regulating the physiological functions [24] . It has been suggested that the metabolites, hormones or neurotransmitters arising from gut microbiota may circulate in the blood and hence affect the physiological functions of the skin. Various diseases, such as inflammatory bowel disease, coeliac disease, rosacea, cutaneous paraneoplasia and Peutz-Jeghers syndrome, have shown manifestations in gut and skin, suggesting a possible pathological relationship between gut and skin. In support of this, the diversity of gut microbiota in the early life seems to possess an inverse relationship to the development of atopic eczema in the later life [25] .