Gut microbiota and c-sections

Mounting evidence shows that the bacterial population of infants’ digestive system, known as gut microbiota, can be influenced by c-sections and formula use. It can no longer be disputed that c-section and formula feeding are both associated with changes to infant microbiota.

I had a c-section. I fed my daughter formula sometimes. So, this made me wonder: Does it matter? What are the consequences of having a different microbiome? This post will focus on c-sections, with one on formula to follow. This is not a formal review or meta-analysis, just my interpretation of a brief review of the literature.

Babies delivered by c-section have different microbiomes than babies delivered vaginally

A 1987 study (1) was the first to show that babies born by c-section have different microbiota than babies born vaginally, measured by the bacteria found in fecal samples shortly after birth. Importantly, there are millions, possibly billions, of different species of bacteria. This initial study found decreased numbers of Bacteroides fragilis (B. fragilis) in babies born by c-section. Follow-up studies found:

At 1 month of age, no differences in Bacteroides, but higher numbers of bifidobacteria in vaginally-delivered babies. The same study found no differences in microbiomes at 6 months. (5)
At 6 weeks of age, higher numbers of Bacteroides in vaginally-delivered babies (7)
At 4 months of age, higher numbers of Shigella and Bacteroides in vaginally-delivered babies (4).
At 6 months of age, higher numbers of Bacteroides in vaginally-delivered babies (2).
At 7 years of age, higher numbers of C. difficile in vaginally-delivered babies (3)
At 7 years age, lower numbers of C. difficile in vaginally-delivered babies (6)

Given that differences in C. difficile were not detected in the studies of younger children, and the existing findings are contradictory, I think it is safe to say that differences in C. difficile are better explained by data artifacts than by mode of delivery. However, the Bacteroides findings have been robustly replicated and seem to hold.

So that brings to mind two questions:

1. How long does this effect persist?

I can’t find any direct investigations of the effect of mode of delivery on microbiota after weaning(except the 2 studies I cited above that are contradictory and do not find differences in Bacteroides), let alone into adulthood. So, the best evidence has to come from a general understanding of the evolution of the microbiome across the lifetime. Is the microbiome stable, persistent, unchanging? Or does it evolve as we go through our lives?

In fact, the microbiome is flexible and adaptive, and changes dramatically over time. By adolescence (13 to 17), a child’s microbiome is no more similar to his/her mother’s than it is to his/her father’s:

“Although biological mothers are in a unique position to transmit an initial inoculum of microbes to their infants during and after birth, our analysis of mothers of teenage US twins showed that their fecal microbiota were no more similar to their children than were those of biological fathers…” (15)

Since, presumably, 0% of the fathers vaginally delivered their children, I think we can infer from this finding that by adolescence, mode of delivery no longer has a detectable effect on the microbiome.

2. Does it matter? What are the consequences of low Bacteroides numbers?

Obesity has been associated with a low ratio of Bacteroides to Firmicutes (11, 12)
Colon cancer has been associated with high Bacteroides numbers (8, 9), specifically B. fragilis (10)
Bacteroides can induce inflammatory bowel disease in susceptible animals (13)

(Credit to [14], review.)

So I would not be quick to say that c-sections cause obesity unless you are equally prepared to claim that vaginal delivery causes colon cancer and inflammatory bowel disease. In both cases, the data are preliminary, and that conclusion is an oversimplification of a complex, evolving system.

Additionally, consider that country of origin has a larger influence on microbiome population than does mode of delivery (7). Which country has the “best” biome? Who knows? What does that even mean? Then how can we say that a baby born by c-section has a worse biome than a vaginally-delivered baby?

Other important confounds:

As I was reading through these studies, I learned that antibiotics are given routinely before/during c-sections as preventive care. That’s what, as a reviewer, I would call a fatal confound. Are changes in Bacteroides populations due to c-sections, or due to antibiotic administration? Would we see similar microbiomes in babies delivered to mothers who had antibiotic administration for other reasons?

Conclusions

I don’t mean to suggest here that c-sections have no consequences for mother or baby, or even for the microbiome. I do think the preponderance of evidence shows that c-sections are associated with changes to the microbiome. I don’t think anyone can categorically say that the microbiome of a c-section baby is worse than the microbiome of anyone else. And if you’re really worried, there are always probiotics.

References

1. http://www.sciencedirect.com/science/article/pii/S0176672487802134

2. http://journals.lww.com/jpgn/Abstract/1999/01000/Fecal_Microflora_in_Healthy_Infants_Born_by.7.aspx

3. http://gut.bmj.com/content/53/9/1388.2.long

4. http://www.cmaj.ca/content/185/5/385.full

5. http://www.ncbi.nlm.nih.gov/pubmed/18025796

6. http://www.sciencedirect.com/science/article/pii/S0091674911011481

7. http://journals.lww.com/jpgn/Fulltext/2010/07000/Intestinal_Microbiota_of_6_week_old_Infants_Across.15.aspx

8. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016393

9. http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2006.01494.x/full

10. http://www.nature.com/ismej/journal/v6/n2/full/ismej2011109a.html

11. http://www.nature.com/nature/journal/v444/n7122/full/4441022a.html