Contrasting Health Effects of Bacteroidetes and Firmicutes Lies in Their Genomes: Analysis of P450s, Ferredoxins, and Secondary Metabolite Clusters

Abstract

Species belonging to the bacterial phyla Bacteroidetes and Firmicutes represent over 90% of the gastrointestinal microbiota. Changes in the ratio of these two bacterial groups were found to have contrasting health effects, including obesity and inflammatory diseases. Despite the availability of many bacterial genomes, comparative genomic studies on the gene pools of these two bacterial groups concerning cytochrome P450 monooxygenases (P450s), ferredoxins, and secondary metabolite biosynthetic gene clusters (smBGCs) are not reported. This study is aimed to address this research gap. The study revealed the presence of diverse sets of P450s, ferredoxins, and smBGCs in their genomes. Bacteroidetes species have the highest number of P450 families, ferredoxin cluster-types, and smBGCs compared to Firmicutes species. Only four P450 families, three ferredoxin cluster types, and five smBGCs are commonly shared between these two bacterial groups. Considering the above facts, we propose that the contrasting effects of these two bacterial groups on the host are partly due to the distinct nature of secondary metabolites produced by these organisms. Thus, the cause of the contrasting health effects of these two bacterial groups lies in their gene pools.

Keywords: Bacteroidetes; Cytochrome P450 monooxygenases; Firmicutes; ferredoxins; human gut microbiome; human health; secondary metabolite gene clusters.

Figure 1

Analysis of P450s in Bacteroidetes species. The number next to the bar indicates the count for that category. Detailed analysis of the species, genera, and P450s are presented in Table S1.

Figure 2

Phylogenetic analysis of Bacteroidetes species P450s. The P450 families that are expanded in these species are displayed in different colors.

Figure 3

Analysis of P450 family absence/presence and co-occurrence in Bacteroidetes species. The data have been represented as −3 for family absence (green) and 3 for family presence (red). There are 77 Bacteroidetes species that form the horizontal axis, and 21 P450 families form the vertical axis.

Figure 4

Comparative analysis of P450 families between Bacteroidetes- and Firmicutes-species. The number in parenthesis indicates the number of members in a P450 family. The numbers indicated with red and blue colors represent the P450 family count for Firmicutes- and Bacteroidetes-species, respectively. Numbers in bold indicate the number of P450 families.

Figure 5

Comparative analysis of secondary metabolite biosynthetic gene clusters (smBGCs) between Bacteroidetes- and Firmicutes-species. The main panel compares cluster types and the inset panel represents overall features between these two bacterial groups. The number next to the bar indicates the count for that category. The cluster type names and abbreviations used in the figure are the standard abbreviations proposed by anti-SMASH [56].

Figure 6

Comparative analysis of ferredoxins iron–sulfur (Fe-S) cluster features between Bacteroidetes- and Firmicutes-species. The number next to the bar indicates the count for that category.