Microbiome studies find lifestyle links, improve understanding of fecal transplants

A number of new studies featured in a special microbiome-focused issue of the journal Science provide new data on the associations between lifestyle and the gut microbiome, as well as a greater understanding of fecal microbiota transplantation.

Lifestyle-Microbiome Associations

Researchers from the Flemish Gut Flora Project presented their first major results since the project’s inception in 2012. Their large population-wide study on the variation of gut microbiota in healthy participants resulted in the identification of 69 factors associated with the composition and diversity of the gut microbiome.

“Our research has given us a tremendous amount of new insight into the microbiota composition of normal people like you and me,” Jeroen Raes, PhD, from the University of Leuven, the Flanders Institute for Biotechnology and the Free University of Brussels in Belgium, said in a press release. “This makes the Flemish Gut Flora Project unique, since the majority of previous studies focused on specific disease or featured a significantly smaller geographical scope. However, analyzing the ‘average’ gut flora is essential for developing gut bacteria-based diagnostics and drugs. You need to understand what’s normal before you can understand and treat disease.”

Raes and colleagues used 16S ribosomal RNA gene amplicon sequencing to analyze stool samples from their “extensively phenotyped” cohort of individuals living in Flanders, Belgium (n = 1,106), collaborated with the Dutch LifeLines study to replicate their findings (n = 1,135), and integrated their results with other global data sets (n = 3,948) to reveal 14 core bacterial genera present in more than 95% of all individuals, and 664 total species overall. However, exploring total western gut diversity would require sampling more than 40,000 additional participants, they wrote.

Of the 69 clinical and questionnaire-based covariates linked to variation of microbiota composition, stool composition and transit time showed the strongest association. Others included age, sex, use of certain drugs (including antibiotics, osmotic laxatives, inflammatory bowel disease drugs, female hormones, benzodiazepines, antidepressants and antihistamine), dietary factors (including fiber, bread, fruit, beer and chocolate consumption), BMI, blood oxygen uptake capacity (previously unidentified), hip circumference and uric acid concentrations. Birth mode or breastfeeding were not found to be associated with adult microbiome composition.

In the Dutch LifeLines cohort, 92% of the covariates were replicated, which “adds a tremendous amount of robustness to the results,” Raes said in the press release. These findings represent just the “tip of the iceberg,” and accordingly, Raes and colleagues are already recruiting volunteers for follow-up studies.

In another study, researchers performed deep sequencing of the gut microbiomes of the 1,135 participants in the Dutch LifeLines study, and found associations between specific microbial species and food, health status and medication.

“In total we found 60 dietary factors that influence the diversity,” Alexandra Zhernakova, PhD, from the University of Groningen Medical Center and Top Institute Food and Nutrition in the Netherlands, said in a press release. “What these mean exactly is still hard to say ... but there is a good correlation between diversity and health: greater diversity is better.”

Zhernakova and colleagues found that features of the Western diet, like higher total energy intake, higher carbohydrate intake, soda consumption, snacking and high-fat milk were linked to lower microbiota diversity, whereas coffee, tea and red wine consumption was linked to increased diversity. They also found that, as expected, antibiotic use was associated with decreased abundance of certain species, and metformin, statins, laxatives and PPIs each had “a strong effect” on the gut microbiota. Notably, they observed that individuals who had heart attacks had lower abundance of Eubacterium eligens bacterium. Finally, they found that several secreted proteins were associated with microbial composition, diversity and functional richness, and chromogranin A showed the strongest association, representing “a high potential as a biomarker for gut health,” the researchers wrote.

Improved Understanding of FMT

Finally, in a third study, Simone S. Li, PhD, from the European Molecular Biology Laboratory in Germany, and the School of Biotechnology and Biomolecular Sciences at University of South Wales in Australia, and colleagues found that compatibility between the gut microbiomes of fecal microbiota transplantation patients and donors may be more important than previously believed.

Aiming to determine the extent of donor microbiota colonization, Li and colleagues performed metagenomic analyses of strain populations in 55 fecal samples from 10 FMT recipients who did not receive antibiotics, before and after the procedure. They also compared the cohort to the metagenomes of 48 healthy FMT-naive Human Microbiome Project participants to contextualize their findings.

They found durable coexistence of donor and recipient microbial strains that persisted for 3 months after treatment. Moreover, they found that new microbial strains from donors were more likely to colonize in recipients if the species was already present in the recipients’ gut, and identified three species in particular that effectively colonized in recipients.

“This implies that if doctors can match donors to patients, the chances of the treatment being a success could improve considerably,” according to a press release. “Looking at strains rather than species of bacterial could also make the therapy effective in conditions where it isn’t currently working.”

“With this method, we can really see if, for example, an antibiotic-resistant strain is replaced by a non-resistant one, so it could help to design stool transplants to work in other conditions beyond C. diff,” Willem de Vos, PhD, a microbiologist from Wageningen University and University of Helsinki, said in the press release.

“Ultimately, the goal is to move from a stool transplant to something more manageable, such as a pill,” Li said in a press release. “Our work shows that this is likely going to be a personalized bacterial cocktail, rather than a one-size-fits-all solution.” – by Adam Leitenberger

Disclosure: Raes and Zhernakova report no relevant financial disclosures. Li reports she received an Australian Postgraduate Award and EMBL Australia International PhD Fellowship. De Vos reports he is an inventor on a patent application related to preventing and/or treating insulin resistance. Please see the full studies for lists of all other researchers’ relevant financial disclosures.

References:

Faloney G, et al. Science. 2016; doi:10.1126/science.aad3503

Li SS, et al. Science. 2016; doi:10.1126/science.aaf2477.

Zhernakova A, et al. Science. 2016; doi:10.1126/science.aad3369.