Growth rate alterations of human colorectal cancer cells by 157 gut bacteria

Abstract

Several bacteria in the human gut microbiome have been associated with colorectal cancer (CRC) by high-throughput screens. In some cases, molecular mechanisms have been elucidated that drive tumorigenesis, including bacterial membrane proteins or secreted molecules that interact with the human cancer cells. For most gut bacteria, however, it remains unknown if they enhance or inhibit cancer cell growth. Here, we screened bacteria-free supernatants (secretomes) and inactivated cells of over 150 cultured bacterial strains for their effect on CRC cell growth. We observed family-level and strain-level effects that often differed between bacterial cells and secretomes, suggesting that different molecular mechanisms are at play.Secretomes of Bacteroidaceae , Enterobacteriaceae, and Erysipelotrichaceae bacteria enhanced CRC cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. In some bacteria, the presence of specific functional genes was associated with CRC cell growth rates, including the virulence genes TcdA in Clostridiales and FadA in Fusobacteriaceae , which both inhibited growth. Bacteroidaceae cells that enhanced growth were enriched for genes of the cobalamin synthesis pathway, while Fusobacteriaceae cells that inhibit growth were enriched for genes of the ethanolamine utilization pathway.Together, our results reveal how different gut bacteria have wide-ranging effects on cancer cells, contribute a better understanding of the effects of the gut microbiome on the human host, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies. 2 5 difficile (47, 48) , Bacteroides sp. (27), and the two potentially beneficial bacteria Lactobacillus casei Shirota (49-51) and Akkermansia muciniphila ATCC BAA-835 TM

Insights from Bacteroides Species in Children with Type 1 Diabetes

“…The viability of HT-29-MTX-E12 cells was impaired by the exposure to the secretome of several P. dorei strains, the strains of B. uniformis and the P. distasonis PtF D14MH1. Recently the impact of the secretome of 157 gut bacteria on the growth rates of 5 colorectal cancer cell lines (CRC), including HT-29 was evaluated [ 90 ], and among these 157 gut bacteria, 12 belonged to the genus Bacteroides comprising the species P. dorei , B. eggerthii , B. fragilis , B. massiliensis, and B. ovatus . The effect of the Bacteroides species on cell growth of HT-29 cell line varied from an enhancement to a decline [ 90 ].…”

“…Recently the impact of the secretome of 157 gut bacteria on the growth rates of 5 colorectal cancer cell lines (CRC), including HT-29 was evaluated [ 90 ], and among these 157 gut bacteria, 12 belonged to the genus Bacteroides comprising the species P. dorei , B. eggerthii , B. fragilis , B. massiliensis, and B. ovatus . The effect of the Bacteroides species on cell growth of HT-29 cell line varied from an enhancement to a decline [ 90 ]. The negative impact of Bacteroides species on the growth of the CRC lines was attributed to the action of lipoproteins at the bacterial surface that have a high affinity for cobalamin, confiscating it from the culture medium, making this crucial vitamin inaccessible to the human cells, hence impairing their growth [ 90 , 91 ].…”

Optimized bacterial DNA isolation method for microbiome analysis of human tissues

“…Another major advantage of this technique is the ability to discriminate between microbial species and analyze their gene content including potential virulence factors (Ranjan et al, 2016). This may be crucial to discriminate between a pathogen and a commensal bacterium at the species level (Taddese et al, 2019). Unfortunately, the application of shotgun metagenomic sequencing to study the microbiome of human tissue is severely limited by the high amount of human DNA present in these samples, which vastly outnumbers the bacterial DNA.…”

“…Another major advantage of this technique is the ability to discriminate between microbial species and analyze their gene content including potential virulence factors (Ranjan et al, 2016). This may be crucial to discriminate between a pathogen and a commensal bacterium at the species level (Taddese et al, 2019).…”

Optimized DNA isolation method for microbiome analysis of human tissues

“…analyze its gene content including potential virulence factors (12). This may be crucial to discriminate between a pathogen and a commensal bacterium at species level (13). Unfortunately, the application of shotgun metagenomic sequencing to study the microbiome of human tissue is complicated due to the large amount of human DNA: large amounts of input DNA are required to reach enough depth for sequence analysis of the microbial DNA fraction.…”