Microbiology and bioinformatics to understand the microbiome
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragón L, Jacquelot N, Qu B, Ferrere G, Clémenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L. 2018. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 359:91-97. doi: 10.1126/science.aan3706 (http://science.sciencemag.org.acces.bibl.ulaval.ca/content/sci/359/6371/91)
The authors show that intake of antibiotics during cancer treatment could negatively influence outcome. They find dans Akkermansia could be linked to success of therapy.
They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila. Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy.
Caroline Mullineaux-Sanders, Jotham Suez, Eran Elinav & Gad Frankel. 2018 Sieving through gut models of colonization resistance. Nature Microbiology. 3:132–140 doi:10.1038/s41564-017-0095-1 (https://www.nature.com/articles/s41564-017-0095-1)
This article reviews the difficulties in colonizing the microbiome by pathogens. They mention different ways the commensal flora impedes colonization such as :
Reports from germ-free and antibiotic-treated mice may suggest a more passive form of colonization resistance in which antibiotics, rather than diminishing the presence of actively protective commensals, could be disrupting the microbial ecosystem in a manner that pathogens are able to exploit.
Chun Loong Ho, Hui Qing Tan, Koon Jiew Chua, Aram Kang, Kiat Hon Lim, Khoon Lin Ling, Wen Shan Yew, Yung Seng Lee, Jean Paul Thiery & Matthew Wook Chang. 2018. Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nature Biomedical Engineering, 2:27–37 doi:10.1038/s41551-017-0181-y https://www.nature.com/articles/s41551-017-0181-y
The authors describe how they engineered a commensal Escherichia coli to process molecules from brocoli and transform it into a cancer inhibiting molecule. [The paper is well explained this Science Translational medecine article] (http://stm.sciencemag.org/content/10/428/eaar7534.full)
The engineered commensal Escherichia coli bound specifically to the heparan sulphate proteoglycan on colorectal cancer cells and secreted the enzyme myrosinase to transform host-ingested glucosinolates—natural components of cruciferous vegetables—to sulphoraphane, an organic small molecule with known anticancer activity. The engineered microbes coupled with glucosinolates resulted in >95% proliferation inhibition of murine, human and colorectal adenocarcinoma cell lines in vitro.
Reichardt N, Vollmer M, Holtrop G, Farquharson FM, Wefers D, Bunzel M, Duncan SH, Drew JE, Williams LM, Milligan G, Preston T, Morrison D, Flint HJ, Louis P. Specific substrate-driven changes in human faecal microbiota composition contrast with functional redundancy in short-chain fatty acid production. ISME J. 2018 Feb;12(2):610-622. doi: 10.1038/ismej.2017.196. Epub 2017 Dec 1. https://www.nature.com/articles/ismej2017196
The authors use culture of feces to evaluate the impact on the gut microbiota of 15 substrastes on fecal microbiota and the production of short-chain fatty acids such as butyrate and propionate.
SCFA production was surprisingly reproducible for the different NDCs investigated here compared with the high microbiota variation between donors, which indicated that different OTUs contributed to NDC breakdown and SCFA formation in the different donors.
Bridgewater LC, Zhang C, Wu Y, Hu W, Zhang Q, Wang J, Li S, Zhao L. Gender-based differences in host behavior and gut microbiota composition in response to high fat diet and stress in a mouse model. Sci Rep. 2017 Sep 7;7(1):10776. doi: 10.1038/s41598-017-11069-4. https://www.nature.com/articles/s41598-017-11069-4
The authors found differences in the microbiome of male and female mice. Strikingly, they observed that stress affected the female microbiome, and not male microbiome.
Male mice were more vulnerable to the anxiogenic effects of the high fat diet, and obese male mice showed decreased locomotion activity in response to stress whereas obese female mice did not. In females, stress caused the gut microbiota of lean mice to more closely resemble that of obese mice.
de Gunzburg J, Ghozlane A, Ducher A, Le Chatelier E, Duval X, Ruppé E, Armand-Lefevre L, Sablier-Gallis F, Burdet C, Alavoine L, Chachaty E, Augustin V, Varastet M, Levenez F, Kennedy S, Pons N, Mentré F, Andremont A. Protection of the Human Gut Microbiome From Antibiotics. J Infect Dis. 2018 Jan 30;217(4):628-636. doi: 10.1093/infdis/jix604. https://academic.oup.com/jid/article/217/4/628/4653556
The authors describe the use of AV132 (adsorbent, activated charcoal) to reduce the side effects of antibiotic treatment on the gut microbiome. This kind of approach would be usefull to determine if the effect of a drug is caused by a drug or if it is mediated by microbiota.
Our most important result was that in human volunteers treated with a clinical 5-day course of oral MXF, DAV132 spared the intestinal microbiome from exposure to free MXF by >99%, without affecting the plasma pharmacokinetics of the antibiotic or causing any serious adverse effects.