If cesarean delivery has a prolonged effect

If cesarean delivery has a prolonged effect on the microbiota, this could contribute to the risk for metabolic diseases later in life. Herein, we explored whether the fecal microbiota differs between adults who reported that they were born by cesarean versus vaginal delivery. For comparison, in the same population we looked for differences in the fecal microbiota with history of appendectomy (Guinane et al., 2013; Randal Bollinger et al., 2007). The appendix, particularly its microbial-rich biofilm, has long been postulated to serve as a repository for repopulating the distal gut following an insult such as diarrheal disease or antibiotic exposure (Randal Bollinger et al., 2007). Whether and how this occurs is unknown, particularly in light of a recent observation that surgically removed appendices contained some taxa that are infrequently found in the distal gut (Guinane et al., 2013). In either case, removal of the GDC-0152 could result in a persistent alteration of the fecal microbiota.
Methods The 16S rRNA V4 region was sequenced by the American Gut Project. The operational taxonomic unit (OTU) table rarefied to 10,000 sequence reads per sample, as well as metadata, was downloaded from the American Gut Project website (https://github.com/biocore/American-Gut/tree/master/data/AG). A current summary is available at http://microbio.me/AmericanGut/static/img/mod1_main.pdf, and details of the OTU picking and taxonomy assignment are available at http://nbviewer.ipython.org/github/biocore/American-Gut/blob/master/ipynb/module2_v1.0.ipynb. Alpha diversity (number of OTUs, Shannon\'s index, Chao1, Phylogenetic diversity_whole tree), UniFrac distance matrix and relative abundance of different taxa were calculated in the Quantitative Insights Into Microbial Ecology (QIIME) pipeline.
Results Of the 1097 participants, cesarean birth was reported as “yes” by 92, “no” by 948, and missing or uncertain by 57. Likewise, appendectomy was reported as “yes” by 155, “no” by 961, and missing or uncertain by 21. Selected characteristics of the participants and associations with cesarean birth and appendectomy history are presented in Table 1. The population in the cesarean birth analysis was 44% male, 93% non-Hispanic Caucasian, and distributed through all U.S. regions. They had a mean age of 46 [standard error (SE) 16] years and a mean BMI of 24 (SE 5). An omnivorous diet was reported by 80%, gluten sensitivity by 19%, and lactose sensitivity by 18%. Weight loss of at least 10lb was reported by 10% and weight gain by 5%. An antibiotic had been used by 11% 2–6 months and 13% 7–12 months before participation. Cesarean birth was significantly associated with younger age, but not consistently with any of the other characteristics. History of appendectomy was significantly associated with older age and with higher BMI, and it tended to be more frequent in U.S. states outside California. Without adjusting for age or any other characteristic, cesarean birth and appendectomy histories had a weak inverse association (P=0.11). In the 1097 fecal specimens, taxa were mapped to 261 bacterial families, 626 genera, and 844 species. Microbiome richness and alpha diversity estimates were not associated with cesarean birth or appendectomy history (Supplemental Table 1). In contrast, composition (beta diversity) of the fecal microbiome differed significantly for participants who reported cesarean birth. Average J–S divergence was strongly associated with cesarean birth at all taxonomic levels, from phylum (permutation P=0.0076) to species (P=0.0041, Table 2). In contrast, age was unrelated to average J–S divergence (R=0.02). As shown in Fig. 1, of four genus-level J–S hierarchical clusters, the prevalence of cesarean birth was 9% in cluster A and 8% in cluster D, whereas cesarean prevalence was high in cluster C (13%) and low in cluster B (0 of 30, P=0.03). Appendectomy history had no association with beta diversity defined by average J–S divergence (Table 2).