Uddanam Kidney Nephropathy Under the Light of Metagenomics Perspective
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In this work, we proposed a research hypothesis which mainly focuses on the role of gut microbiota, in relation with chronic kidney disease, existing in the village of Uddanam belonging to the State of Andhra Pradesh, India. Earlier studies conducted on various physical and chemical parameters, such as food, water, soil and pesticides, could not find the exact cause of the aetiology of the disease. As there were no physical and chemical causative factors identified, this disease was hence named as mysterious Uddanam kidney nephropathy of unknown origins. There are few scientific pieces of evidence available in the literature, which suggests the role of gut microbiome dysbiosis and its impact on kidney disease. Such kinds of scientific studies which deal with the analysis of microbial communities of the gut region and identification of dysbiosis were not performed in the case of Uddanam kidney nephropathy. Thus, through this paper, we propose a hypothesis to analyse and establish the relationship between the gut dysbiosis and renal failure by performing the metagenomics study between the patients and the normal individuals. To the best of our knowledge, there are no reports available to date on the dysbiosis of the gut microbiome and its impact on Uddanam nephropathy and hence this research hypothesis is thus proposed.
KeywordsUddanam region Kidney nephropathy Aetiology Andhra Pradesh India Metagenomics
The Uddanam region is geographically located in the south-eastern part of Srikakulam District of the Andhra Pradesh State in India. Recently, the Uddanam region has become very popular for its “Chronic kidney disease of unknown origin”. As of the year 2015–2016, it was estimated that about 34,000 people had this disease and about 4500 people died [1, 2]. The scientific literature and evidence related to this disease aetiology are very limited. To understand the aetiology of this chronic kidney disease (CKD), the physical and chemical causative factors such as soil, water, food, heat stress, pesticides and environmental samples were analysed by different research groups, but failed to provide the clues about the exact causative factors [2, 3, 4, 5, 6]. It was observed that the majority of people who are affected by this kidney disease in the Uddanam region are agriculture labourers . In the year 2013, this CKD of the Uddanam region was named as Uddanam Nephropathy at the International Congress of Nephrology, China.
In the past, there are few studies which have reported about the relationship between the alteration of the gut microbiome and renal failure [7, 8, 9, 10, 11, 12, 13, 14, 15]. On the other hand, there are also few reports describe about the CKDs but does not establish any kind of relationship between physical, chemical and metabolic factors, responsible for the renal failure. Such type of CKDs were named as chronic kidney disease with an unknown origin (CKD-u) . Uddanam kidney disease is also one of the CKDs which was considered as CKD-u . As the analysis performed on the physical and chemical factors could not provide any clues about the exact cause of this CKD. In this report, we propose a hypothesis which may elucidate the relationship between alteration of the gut microbiome (Biological factor) and Uddanam CKD by the use of the concepts of metagenomics and its data analysis.
To proceed with the study, selection of correct participants and a collection of samples (blood and stools) have to be carried out according to the guidelines followed in the earlier reports [17, 18]. For applying the metagenomics approach, collection of fresh stools, their storage, DNA isolation, sequencing, pre-processing of the obtained data, assignment of operational taxonomic units, calculations of the abundance of bacterial families and their distributions between the patients and control samples have to be performed similarly as described in the previous reports .
By performing the comparative analysis on the metagenome data of the patients and control samples, we may clearly identify the dysbiosis between the patients and the normal individuals.
The basic assumption of our hypothesis is that in general at the time of birth human babies are sterile, without any contamination . Later, the newborn is contaminated by bacteria due to the contact of the newborn with the vaginal fluids at the time of delivery. From that point of contact, the bacteria start colonising in different parts of the human body, such as the gastrointestinal tract (GIT) and mouth, and give rise to unique microbial communities . The GIT of a healthy human being is mainly composed of more gram-negative bacteroidetes and low-GC firmicutes . This “healthy gut microbiota” coevolves with the humans for their beneficial coexistence. In harsh conditions, when the healthy microbiome is exposed to various harsh environmental factors which include diet, toxins, drugs and also pathogens, then there is a change/alteration in composition and structure of healthy microbiota, termed as dysbiosis [7, 21].
Dysbiosis was proven to be one of the important causative factors for diseases such as obesity, type 2 diabetes, bowel disease, cardiovascular disease, cancer and asthma [20, 22, 23, 24, 25, 26, 27, 28, 29]. Now a days, there are an increasing number of evidences recorded, which state that due to dysbiosis there might be the progression of CKD and CKD-related problems [30, 31]. It was found that due to gut dysbiosis, the concentrations of the endotoxins are increased due to the processes such as fermentation carried out by pathogenic bacteria in the gut region . As a result of such activities, the products which are formed due to these activities like endotoxins such as phenols, indoles and amines cross the intestinal barrier, and then mix with the bloodstream . As there is an increase in the concentrations of some of the uremic toxins, it may lead to less production of reno-protective metabolites, which generally protect the kidneys . Moreover, it was also reported that alteration in the composition of gut microbiome may lead to the circulation of high levels of lipopolysaccharides, which may further lead not only to immune de-regulation, but also may cause complete renal failure . On the other hand, there are several reports suggesting the role of genetic polymorphisms in the genes APOL1 and MYH9 and their role in CKD. From the literature survey, we observed that the genes APOL1 and MYH9 co-segregate with each other . However, it was proposed that the gene APOL1 is more intensely associated with CKD than the MYH9 gene [36, 37]. But to the best of our knowledge, these are reported from the different parts of the world, especially by analysing the data obtained from the populations of African, African-Americans, Brazilians and European-Americans [35, 38, 39, 40]. However, there are no reports existing in the literature describing the role of APOL1 or MYH9 genes or their genetic polymorphisms in CKD of Indian population [41, 42]. Thus, as there are strong evidence describing the negative correlation between the APOL1 and MYH9 gene involvement in CKD in Indian population, characterising the gut microbiome and identification of the dysbiosis in the microbial content would be a better option, since there is a strong positive correlation established between the gut dysbiosis and CKD from earlier studies.
In the case of Uddanam nephropathy, there are no studies reported to the date about the bacterial composition of healthy GIT and altered GIT of CKD patients (dysbiosis). Moreover, there is no documented evidence available about the comparison of normal healthy GIT microbiota and CKD-affected ones. After careful examination of the published literature, this hypothesis is proposed in the form of this report. This report is the first of its kind to provide research idea for the scientific community to resolve the kidney disease of Uddanam by the use of metagenomics and to elucidate the dysbiosis factors existing between the healthy and the patients. This will ultimately help the many individuals suffering from this disease.
The corresponding author thanks the Institute of Bioinformatics and Computational Biology (IBCB), Visakhapatnam, Andhra Pradesh, India, for its help in securing the news for local incidences of this study. The corresponding is also thankful for Chaitanya Bharathi Institute of Technology (CBIT), Gandipet, Hyderabad, Telangana for providing the facilities to communicate this manuscript.
Research in YA lab is funded by the Department of Biotechnology (Ministry of Science & Technology, Government of India) and Indian Council of Medical Research.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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