Recent investigations have highlighted the dysbiosis of the skin microbiome in leprosy patients. All of those studies are conducted in Brazil and India. From a 16S rRNA gene dataset, we provide the first description of Indonesian leprous skin lesions both before treatment, during treatment, during treatment with reversal reaction, and release from treatment compared to healthy individuals.
Leprous skin lesions revealed five dominant phyla represented by Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, and Cyanobacteria. The same first four phyla were consistent with the previous studies on the skin microbiome of leprosy patients in Brazil and India.7,8,9 However, the fifth phyla (Cyanobacteria) has not been mentioned in the previous studies of skin microbiome in leprous skin lesions. Cyanobacteria (blue-green algae) are common inhabitants of water (fresh, brackish, and marine) and terrestrial environments throughout the world. This phylum produces a broad spectrum of secondary metabolites– biologically active products, which could be toxic (cyanotoxins). The cutaneous adverse effects of cyanobacteria and their cyanotoxins are often underdiagnosed. Cyanobacteria has been reported can cause an irritant and allergic contact dermatitis and also generalized urticarial rash.19 However, until recently the relationship between Cyanobacteria and leprosy is still unknown.
In this study, the result of Proteobacteria which was slightly overrepresented in leprosy patients and Actinobacteria which was underrepresented in leprosy patients compared to healthy individuals were consistent with the previous studies by Silva et al. in 2015. In this study, Firmicutes was overrepresented in leprosy patients and Bacteroidetes was underrepresented in leprosy patients compared to healthy individuals. These findings were different with previous studies by Silva et al. in 2015 and 2018, and also Bayal in 2019. The differences in the results of these studies are thought to be due to differences in the anatomical locations of the study samples. In this study, all samples were taken from the back, because all leprosy patients had skin lesions on the back, whereas in the study conducted by Silva et al.7,8 samples were taken from the volar forearm. In addition, other factors that can affect the microbiome such as gender, age, diet, ethnicity, climate, and geographic location can also cause differences in the results of this study.8,12−14
Staphylococcus and Acinetobacter were the highest abundance genera in leprous skin lesions. These results were different from a previous study conducted by Silva et al.7 in 2015 in Brazil, which was Bacillus genera was the highest genera found in the leprous skin lesions. From the results of a study conducted by Bayal et al.9 it was found that the group of leprosy patients during treatment in Hyderabad and Miraj areas of India had a significantly different skin microbiome. Based on a study conducted by Blaser et al.20 in the United States and Venezuela in 2012 which compared the skin microbiome on the forearm between a population of healthy individuals in the United States and Venezuela. It was found that there were differences in the skin microbiome of the two populations. The difference in results between this study and that of Silva et al. and Bayal et al. presumably because the skin microbiome can be influenced by ethnicity, lifestyle, and/or geographic location.8,12−14
Propionibacterium and Corynebacterium genera were diminished in leprous skin lesions compared to healthy individuals. Similar results were shown in previous study conducted by Silva et al.7 Propionibacterium and Corynebacterium were the dominant genera in healthy skin.21,22 Both of these genera have a protective function in the skin of healthy individuals.7 One of the species of the genus Propionibacterium, namely Propionibacterium acnes can inhibit the growth of pathogenic bacteria, such as Staphylococcus aureus and Streptococcus pyogenes through the formation of free fatty acids and propionic acid, as well as the secretion of bacteriocins, such as thiopeptide.13 Therefore, the decreased number of Propionibacterium and Corynebacterium genera in the leprous skin lesions are thought to be due to interference with the skin's protective function.7
Leprosy reactions can occur due to changes in the immune system in leprosy patients.23 In reversal reaction, the role of T helper (Th)1 is more dominant than Th2. The existence of dysregulation of the immune system such as increased Th1 activity can cause changes in the composition of the microbiota and otherwise.24 Based on the results of this study, there were differences in the order of the microbiota phylum (Firmicutes and Actinobacteria) and genera (Micrococcus and Propionibacterium) composition in leprosy patients during treatment with and without reversal reaction. This result indicate the possibility of reversal reaction influence on microbiome composition. To the best of our knowledge, this was the first report of the skin microbiome in leprosy with reversal reaction..
The top five species in all of groups in this study were Acinetobacter johnsonii, Micrococcus luteus, Moraxella atlantae, Pseudomonas stutzeri, and Ensifer adhaerens, with the first four species were enriched in leprosy patients, while Ensifer adhaerens was diminished in leprosy patients when compared with healthy individuals. Acinetobacter johnsonii, Micrococcus luteus, Moraxella atlantae, and Pseudomonas stutzeri have been reported previously as a pathogen bacteria that can cause some diseases, such as meningitis (Acinetobacter johnsonii, Micrococcus luteus, Pseudomonas stutzeri), bacteriemia in adenocarcinoma patient (Moraxella atlantae), and ecthyma gangrenosum (Pseudomonas stutzeri).25–28 Factors that cause the four species mentioned above are found to be more in the leprous skin lesions than healthy individuals is not known, but it is possibly due to autonomic nerve damage in leprous skin lesions which causes dry skin and impaired protective role of the skin.1 In contrast to the four previous species, Ensifer adhaerens was higher in healthy individuals compared to leprous skin lesions. Ensifer adhaerens is a Gram-negative bacteria from soil and has lysis properties for other Gram-positive and negative bacteria.29 The presence of this species on human skin has not been previously reported.
Mycobacterium leprae was not found in this study, which was same as the previous study.7,8 It is possibly because of the skin swab as a sampling procedure, since this bacteria is an obligate intracellular pathogen of macrophages.1,2,8
Based on this study, there were 22 genera and 25 species of microbiota, which were only found in the leprous skin lesions. These genera and species are not commonly found on human skin. According to those circumstances, these thought to be a potential pathogen, and its existence is probably caused by an impaired skin barrier of protective function in leprosy patients.
The alpha diversity in the leprous skin lesions in this study was lower than that of healthy individuals. These results were similar to previous study conducted by Silva et al.8 in 2018 in Brazil and Bayal et al.9 in 2019 in India. Studies on alpha diversity in skin microbiome have been conducted in several other skin diseases, such as atopic dermatitis and psoriasis. Therefore, it was known that the diversity of the microbiome was found to be lower in these two diseases than in healthy individuals.30,31 In atopic dermatitis, the decrease in the diversity of the microbiome is related to the degree of disease severity and increased colonization of pathogenic bacteria, such as Staphylococcus aureus.32 This proves that some diseases can reduce the diversity of the skin microbiome including in leprosy.