The Association Between Serum Ferritin and The Gut Microbiome in Patients with Active Tuberculosis Disease in South India
Background: Tuberculosis is one among the primary top ten causes of death and is the leading cause of a single infectious agent. Tuberculosis is a consequence of a rather particular immune failure against M. tuberculosis. Thus, evaluating the role of essential factors including serum ferritin and the gut microbiome in modulating the host immune system is vital in providing a better understanding of the complexity of the TB disease process. To our knowledge, no studies have been conducted to evaluate the role of serum ferritin to the gut microbiome in TB disease. The objective of this study was to characterize the composition and diversity of the gut microbiome by the level of serum ferritin in patients with new Active Tuberculosis Disease (ATBD). Methods: In this cross-sectional study, all participants (n=32) were adult patients with new ATBD who attended an outpatient hospital, Arogyavaram Medical Centre (AMC), in Madanapalle, South India. Active pulmonary Tuberculosis disease was confirmed by Xpert MTB/RIF. Serum ferritin levels in this population were evaluated by Chemiluminescence immunoassay (ng/mL) and categorized as normal (15-250 ng/mL) or high (>250 (ng/mL), and by tertile in this population. Rectal swab samples were collected for DNA extraction, amplification and 16s rRNA sequencing (V3-V4 region; Illumina Miseq). Quantitative Insights into Microbial Ecology (V1.9.0) and GreenGenes 13.8 were used in taxonomy assignment of sequences and analysis sequenced data. Results: The median of serum ferritin was 350.1 ng/mL (IQR, 179.1-719.15). About 68.75% participants had elevated serum ferritin. The gut microbiome predominantly belonged to five phyla (median (IQR): Firmicutes (46.1% (36.5-51.6)), Bacteroidetes (32.4% (24.5-40.4)), Proteobacteria (9.3% (6.1-28.1)), Actinobacteria (2.1% (1.3-4.2)), and Fusobacteria (0.3% (0.0-3.8). At the genus level, sequences predominantly were: Prevotella (11.7% (4.0-24.3)), Bacteroides (5.0% (1.2-14.3)), Faecalibacterium (4.8% (1.5-6.5)), 1-68 (0.2% (0.0-2.0)), Phorphyromonas (0.4% (0.0-2.2)), and WAL_1855D (0.2% (0.0-1.7). The relative abundance of phylum and genus did not differ significantly by the level of serum ferritin (Normal or High, tertiles, p>0.05). Alpha diversity (Chao1, Observed-species, Shannon, Simpson) also did not differ by the serum ferritin level (p>0.05). The Firmicutes phylum and Prevotella genus were found to be negatively associated with serum ferritin (p<0.05). Bacteroides genus was observed to be positively associated with serum ferritin (p<0.05). Conclusions: The changes of the composition of the gut microbiome such as changes of relative abundance of Firmicutes phylum, Prevotella and Bacteroides genera could have related to serum ferritin as a part of the immune response against M. tuberculosis. The findings from our study might as well related to the characteristic of Prevotella and Bacteroides that unable to synthesize heme and have the essential requirement of a high amount of iron and its precursors for growth. Further longitudinal studies with multiple time points and larger sample sizes are required to evaluate the role of serum ferritin to the gut microbiome of tuberculosis-infected patients.
Ferritin; Iron; Gut Microbiome; tuberculosis; Nutrition
Strupp, Barbara Jean
Master of Science
dissertation or thesis