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The New Biome in Town

Breaking down the microbiology world one bite at a time

The New Biome in Town

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janagomez

One of the newer microbiology sub-fields that has risen to popularity this century is microbiome studies. A microbiome refers to a group of microorganisms that live in harmony with humans. Some of the more well-studied microbiomes include the gut microbiome, the skin microbiome, and the oral microbiome.

Recent advances in technology have uncovered new microbiomes, particularly one in a part of the body that was commonly thought of as sterile. In 2014, Hilt, et. al used various new methods of urine culturing to accurately define the urobiome, or the microbiome of the urinary tract. This debunked the previously held idea that urine was free of microbes. 

Since this finding, many scientists have gone on to further characterize the urobiome. Importantly, studies have shown that changes in the species that exist in the urobiome, also called dysbiosis, are associated with disease. Bacterial species that are commonly identified in the bladder of individuals with urinary tract infections (UTI) include various pathogens, such as Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. 

These bacteria not only are more commonly identified in the urinary tract of patients that have UTIs, but they are also commonly associated with kidney stone formation. Since these microbes are known to cause problems in the kidneys, the authors of this study wondered if there was also a unique microbiome in the upper urinary tract (kidneys), just like there was in the lower urinary tract (bladder).

To answer this question, these researchers needed to be creative with their sample collection. Since there is a known urobiome, they could not take urine samples to determine if there were microbes in the kidneys without the risk of contamination. So instead, these researchers utilized biopsies of mouse kidneys in order to see if microbes were found in this organ. Indeed, the authors found that as you moved from the renal cortex (the outer layer of the kidney) to the medulla (the inner layer of the kidney), then to the ureter (the tube that carries urine from the kidneys to the bladder), the bacterial density increased (Figure below). This showed that microbes were indeed living inside of the kidneys.

Proportion of bacteria throughout the urinary tract. The bacterial density increases as you move from the renal cortex to the medulla, and finally to the ureter. Made by the author in Canva.

But what specific microbes were living there? To answer this question, the authors utilized rRNA sequencing. Interestingly, the species composition of microbes was different between the bladder and the kidneys. Acinetobacter was the most enriched species in the urine, whereas the kidneys were mostly enriched with Pseudomonas species. 

Next, the authors wanted to determine how antibiotics affect the kidney microbiome. To do this, the authors gave mice a commonly used antibiotic, cefazolin. Interestingly, groups of bacteria that were known to cause UTIs significantly increased in the mice that were given cefazolin. The authors also observed that Lactobacillus, a microbe that is commonly associated with decreased kidney stones, was less prevalent in the kidneys of mice exposed to antibiotics.

The increase of these pathogens and decrease of healthy microbes in the presence of antibiotics was concerning, but hope is not lost! Now that we know what microbes are native to the kidneys and which ones help prevent disease, new therapies can be developed that focus on restoring the healthy kidney microbiome. 

The advancement of increasingly accurate and sensitive sequencing methods, like the ones used in this study, continue to advance the microbiology field forward. Who knows what new biome will be discovered next!

Link to the original post: Agudelo J, Chen X, Mukherjee SD, Nguyen JK, Bruggeman LA, Miller AW. Cefazolin shifts the kidney microbiota to promote a lithogenic environment. Nat Commun. 2024 Dec 11;15(1):10509. doi: 10.1038/s41467-024-54432-6. PMID: 39663374; PMCID: PMC11634958.

Additional Sources:

  1. Kachroo N, Monga M, Miller AW. Comparative functional analysis of the urinary tract microbiome for individuals with or without calcium oxalate calculi. Urolithiasis. 2022 Jun;50(3):303-317. doi: 10.1007/s00240-022-01314-5. Epub 2022 Mar 2. PMID: 35234986; PMCID: PMC11247624.
  2. Hilt EE, McKinley K, Pearce MM, Rosenfeld AB, Zilliox MJ, Mueller ER, Brubaker L, Gai X, Wolfe AJ, Schreckenberger PC. Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol. 2014 Mar;52(3):871-6. doi: 10.1128/JCM.02876-13. Epub 2013 Dec 26. PMID: 24371246; PMCID: PMC3957746.

Featured image: Made by the author in Canva