Healthy Microbiome: A Work in Progress, Plus Microbiome-Drug Metabolism

A recent study (G Galazzo, N Van Best, et al. Gastroenterol 2020; 158: 1584-96) highlights the changes in microbiota diversity from birth until 11 years of age.

Full text: Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood

Methods: We collected 1453 stool samples, at 5, 13, 21, and 31 weeks postpartum (infants), and once at school age (6–11 years), from 440 children (49.3% girls, 24.8% born by cesarean delivery; all children except for 6 were breastfed for varying durations; median 40 weeks; interquartile range, 30–53 weeks).

Key findings:

  • Most bacteria within the Bacteroidetes and Proteobacteria phyla were already present at 5 weeks after birth, whereas many bacteria of the Firmicutes phylum were acquired at later times in infancy.
  • At school age, many new Actinobacteria, Firmicutes, and Bacteroidetes bacterial taxa emerged.
  • The largest increase in microbial diversity occurred after 31 weeks of life.
  • Vaginal, compared with cesarean delivery, was most strongly associated with an enrichment of Bacteroides species at 5 weeks through 31 weeks.
  • From 13 weeks onward, diet became the most important determinant of microbiota composition; cessation of breastfeeding, rather than solid food introduction, was associated with changes.
  • When we adjusted for confounding factors, we found fecal microbiota composition to be associated with development of atopic dermatitis, allergic sensitization, and asthma. Members of the Lachnospiraceae family, as well as the genera Faecalibacterium and Dialister, were associated with a reduced risk of atopy.

My take: We are still learning a lot about the microbiome.  Though a ‘healthy’ microbiome is still not straight-forward determination, a good diet with plenty of fruits and vegetables has been associated with more favorable attributes.

Plus One: Bahar Javdan, et al. Personalized Mapping of Drug Metabolism by the Human Gut MicrobiomeCell, 2020; DOI: 10.1016/j.cell.2020.05.001

In this study, the authors found how variations in the microbiome had unique effects on drug metabolism.  From ScienceDaily, Can gut microbiome alter drug safety and efficacy?  The authors tested 575 FDA-approved drugs to see if they are chemically modified by one of the 21 cultured microbiomes, and then tested a subset of the drugs with all the cultured microbiomes. Here, they found microbiome-derived metabolites that had never been previously reported

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Is It a Good Idea for Pregnant Mothers to Take Probiotics?

A previous study has indicated that maternal probiotic administration was associated with a lower rate of atopic dermatitis.  The overall quality of evidence supporting this association is considered low.

A recent study (CK Dotterud et al. JPGN 2015; 61: 200-7) examined the effect on the intestinal microbiota in both mother and child following maternal perinatal probiotic supplementation. This randomized, double-blind trial examined the effect of probiotic administration (or placebo) from 36 weeks of gestation up to 3 months postnatally while breastfeeding. Stool microbiome was examined in both mother and child.

Key findings:

  • The changes in the infants microbiome were quite limited. “Only the Lactobacillus rhamnosus GG bacteria colonized the children at 10 days and at 3 months of age. There were no significant differences in the abundance of administered probiotic bacteria between the groups at 1 and 2 years of age.”

My take: We know very little about probiotics and their effects on the GI tract. We often do not even the basics: which strains? which dosage?  optimal timing/when to use?  Given the lack of persistent change in the infant’s microbiome, does administration to pregnant mothers really make any sense (outside of research endeavors)?