In Silico Analysis of Antibiotic Resistance Genes in the Gut Microflora of Individuals from Diverse Geographies and Age-Groups

Abstract

The spread of antibiotic resistance, originating from the rampant and unrestrictive use of antibiotics in humans and livestock over the past few decades has emerged as a global health problem. This problem has been further compounded by recent reports implicating the gut microbial communities to act as reservoirs of antibiotic resistance. We have profiled the presence of probable antibiotic resistance genes in the gut flora of 275 individuals from eight different nationalities. For this purpose, available metagenomic data sets corresponding to 275 gut microbiomes were analyzed. Sequence similarity searches of the genomic fragments constituting each of these metagenomes were performed against genes conferring resistance to around 240 antibiotics. Potential antibiotic resistance genes conferring resistance against 53 different antibiotics were detected in the human gut microflora analysed in this study. In addition to several geography/country-specific patterns, four distinct clusters of gut microbiomes, referred to as ‘Resistotypes’, exhibiting similarities in their antibiotic resistance profiles, were identified. Groups of antibiotics having similarities in their resistance patterns within each of these clusters were also detected. Apart from this, mobile multi-drug resistance gene operons were detected in certain gut microbiomes. The study highlighted an alarmingly high abundance of antibiotic resistance genes in two infant gut microbiomes. The results obtained in the present study presents a holistic ‘big picture’ on the spectra of antibiotic resistance within our gut microbiota across different geographies. Such insights may help in implementation of new regulations and stringency on the existing ones.

Antibiotics and the gut microbiota

“…With an estimated 1% to 3% of the developed world undergoing antibiotic treatment on a daily basis (3), the dynamic environment of the human intestine benefits (and may suffer in some cases) from metagenome accessibility of these genes on conjugative elements, viral particles, and plasmids (46,(52)(53)(54). Interestingly, in a study of genomic variation in over 200 individuals, conjugative elements with resistance functions were found to have the highest SNP density of all annotatable genes (55).…”

Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes

“…The study also found multiple antibiotic resistance genes on contigs with integrase and transposase, indicating the possibility that these clusters are part of mobile genetic elements, such as conjugative transposons. Furthermore, 97% of the gut metagenomes harbored resistance genes to tetracycline, 95% to bacitracin, and 95% to tetracycline 59. Another metagenome analysis evaluated the gut microbiome from 162 individuals (encompassing 4.1 million genes) and found 1,093 antibiotic resistance genes 60.…”

The Threat of Antimicrobial Resistance on the Human Microbiome

“…Analysis of resistance against 68 classes and subclasses of antibiotics in 252 fecal metagenomes of individuals from three countries, Spain, Denmark and the U.S., show that global resistomes are significantly impacted by antibiotics approved for animal use as well as those that have been in use for the longest time [90]. The existence of these global “resistotypes” has also been shown in other studies, pointing to resistance to tetracycline as the most common genotype among individuals from different nationalities, and increased abundance and diversity of AMR in Spanish, Chinese, French or Italian cohorts compared to cohorts of Americans or Danish people [59, 90, 91]. …”

“…Tcr genes are also shared between mothers and infants; however, encoded by different organisms; Bacteroides , Ruminococcaceae and Clostridiaceae like taxa in mothers; and Streptococci in infants [57]. Nonetheless, other reports point to an infant gut resistome that is unique and different from that of the mothers, and that includes resistance to broad-spectrum β-lactam antibiotics, suggesting that early environmental determinants (different from maternal ones) also shape AMR development in the infant gut [58, 59]. In fact, lifestyle factors related to subsistence, diet and other cultural drivers strongly shape the GI microbiome [60, 61].…”