Another area of gut-lung axis research involves microbial-derived metabolites, such as short chain fatty acids (SCFAs). SCFAs are direct by-products of bacterial fermentation of carbohydrates and are key energy sources for many host tissues and gut bacterial species [
51]. There are three major SCFAs, acetate, propionate, and butyrate, which are present in a molar ratio of 60:20:20, respectively [
51]. These metabolites are known to modify gene expression through inhibition of histone deacetylases (HDACs), cytokine and chemokine production, and cell differentiation, proliferation, and apoptosis [
52]. With regard to immune tolerance and inflammatory mechanisms, butyrate and propionate induce extrathymic T-regulatory (T-reg) generation through direct interactions with T cells and indirect interactions through DCs, potentially through the inhibition of HDACs [
53]. Clostridial species are prominent SCFA producers, and butyrate production by these particular bacteria was associated with the generation of peripheral T-reg cells in the colon [
54]. In a HDM-mouse model of experimental asthma, both acetate and propionate were capable of reducing cellular infiltration into the airways after HDM exposure [
55]. Systemic propionate treatment modified bone marrow hematopoiesis and enhanced the generation of DC and macrophage precursors and subsequent recruitment of DCs less effective in promoting Th-2 cell polarization in the lungs [
55]. In a later study using the same asthma mouse model, maternal intake of acetate was shown to reduce allergic airways disease in the adult offspring of mice [
56]. Notably, both these studies initially assessed the role of a high fiber diet on the production of SCFAs and colonization of intestinal bacteria—highlighting the influence of diet, mediated by gut microbial changes, on the development of the immune system [
55,
56]. The latter study, however, emphasizes intrauterine effects on the infant immune system, mediated by maternal diet, suggesting the need to consider prenatal prevention strategies using these gut microbial metabolites [
56].