By Dr. Geoffrey Modest
Last March I sent out a blog reviewing a Finnish study that found changes in intestinal colonization in those traveling to a variety of places, including South Asia and Sub-Saharan Africa, looking at a few specific resistant bacteria (extended-spectrum beta-lactamase-producing Enterobacteriaceae and carbapenemase-producing Enterobacteriaceae), and finding significant colonization overall but especially in those who developed traveler’s diarrhea and even much more so in those who took antibiotics for it (see https://stg-blogs.bmj.com/bmjebmspotlight/2015/03/19/primary-care-corner-with-geoffrey-modest-md-travelers-diarrhea-the-treatment-may-be-worse-than-the-disease/ ).
The current study adds greatly to the concern about GI microbiome changes with travel by looking at the larger microbiome, not just a couple of concerning species as above (see doi:10.1128/AAC.00933-15).
Details:
- They used “explorative shotgun metagenomic sequencing” (???? you might ask — turns out to be a new technology to do quantitative analysis of pretty much all known antibiotic-resistance genes, >300 genes, in a single assay looking at the total DNA of the gut, whether the bacteria is cultivable or not) in 35 Swedish students aged 23-34, 74% female, comparing their fecal samples before and after exchange programs in the Indian peninsula (n=18) or in Central Africa (n=17), from 2010-2013. The median travel duration was 34 days. None were exposed to antibiotics, though 23 of the 35 did participate in hospital-based patient work. In doing the metagenomic sequencing, they limited their assessment to genes conferring verified resistance phenotypes (i.e., those genes known to be associated with resistant bacterial infections).
- 69% (12 of 17 going to Central Africa and 12/18 to the Indian peninsula) had travelers’ diarrhea for a median of 4 days.
- None were exposed to antibiotic treatment in the 6-month period before or during the travel, though those who went to Central Africa did have antimalarial chemoprophylaxis (mostly mefloqine, which may have some broader antibacterial effect).
Results:
- The overall taxonomic diversity and composition of the microbiome was pretty stable from before to after travel, though there was an increase in Proteobacteria in 25 of the 35 students (Proteobacteria have been associated with inflammatory conditions in the large bowel, including ulcerative colitis, difficile enteritis, and chronic HIV).
- BUT, there was an overall increase in the abundance of antibiotic resistance genes, especially for those encoding resistance to:
- Sulfonamides (2.6-fold increase)
- Trimethoprim (7.7-fold increase)
- Beta-lactams (2.6-fold increase)
- And significant increases, but less profound, for aminoglycosides and tetracycline
- Of those traveling to the Indian peninsula, 12 acquired extended-spectrum beta-lactamase-producing (ESBL) E. coli, though none from Africa. Of some concern, these were not picked up on the above genetic sequencing, likely because the sensitivity of the assay was insufficient for low-abundant genes.
- The above microbiome changes were not significantly related to those who reported experiencing traveler’s diarrhea (and, as mentioned, none had taken antibiotics)
So, a few observations:
- This metagenomic technique appears to be pretty powerful in assessing microbiome changes, though not perfect (e.g., it missed some ESBL E. coli)
- In general, we think of the major changes in microbiome being from use of antibiotics, poor infection prevention/control within health care systems, poor sanitation, antibiotic pollution of the environment (e.g. massive use of antibiotics for animals), international food trade and travel. I would add to this list other medications and dietary/lifestyle changes (as delineated in prior blogs), though I think this study does raise the issue of travel-acquired changes even more. We do not know if there was any transmission of antibiotic-resistant genes back home or even if the microbiome changes continued/for how long (the final stool samples were a median of 3 weeks after return from travel, with max of 4 months). We don’t even know if the quantitative increase in antibiotic resistance genes is associated with clinical disease. In addition, it would be useful to know if others living with the travelers had any changes in their microbiomes. but, overall, the microbiome changes from travel are still concerning and have the very real potential to lead to difficult-to-treat diseases spreading throughout the world, and doing so more often as more antibiotic resistance continues to develop.