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1. Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Author

Edwards, Robert A., Vega, Alejandro A., Norman, Holly M., Ohaeri, Maria, Levi, Kyle, Dinsdale, Elizabeth A., Cinek, Ondrej, Aziz, Ramy K., McNair, Katelyn, Barr, Jeremy J., Bibby, Kyle, Brouns, Stan J. J., Cazares, Adrian, de Jonge, Patrick A., Desnues, Christelle, Díaz Muñoz, Samuel L., Fineran, Peter C., Kurilshikov, Alexander, Lavigne, Rob, Mazankova, Karla, McCarthy, David T., Nobrega, Franklin L., Reyes Muñoz, Alejandro, Tapia, German, Trefault, Nicole, Tyakht, Alexander V., Vinuesa, Pablo, Wagemans, Jeroen, Zhernakova, Alexandra, Aarestrup, Frank M., Ahmadov, Gunduz, Alassaf, Abeer, Anton, Josefa, Asangba, Abigail, Billings, Emma K., Cantu, Vito Adrian, Carlton, Jane M., Cazares, Daniel, Cho, Gyu-Sung, Condeff, Tess, Cortés, Pilar, Cranfield, Mike, Cuevas, Daniel A., De la Iglesia, Rodrigo, Decewicz, Przemyslaw, Doane, Michael P., Dominy, Nathaniel J., Dziewit, Lukasz, Elwasila, Bashir Mukhtar, Eren, A. Murat, Franz, Charles, Fu, Jingyuan, Garcia-Aljaro, Cristina, Ghedin, Elodie, Gulino, Kristen M., Haggerty, John M., Head, Steven R., Hendriksen, Rene S., Hill, Colin, Hyöty, Heikki, Ilina, Elena N., Irwin, Mitchell T., Jeffries, Thomas C., Jofre, Juan, Junge, Randall E., Kelley, Scott T., Khan Mirzaei, Mohammadali, Kowalewski, Martin, Kumaresan, Deepak, Leigh, Steven R., Lipson, David, Lisitsyna, Eugenia S., Llagostera, Montserrat, Maritz, Julia M., Marr, Linsey C., McCann, Angela, Molshanski-Mor, Shahar, Monteiro, Silvia, Moreira-Grez, Benjamin, Morris, Megan, Mugisha, Lawrence, Muniesa, Maite, Neve, Horst, Nguyen, Nam-phuong, Nigro, Olivia D., Nilsson, Anders S., O’Connell, Taylor, Odeh, Rasha, Oliver, Andrew, Piuri, Mariana, Prussin II, Aaron J., Qimron, Udi, Quan, Zhe-Xue, Rainetova, Petra, Ramírez-Rojas, Adán, Raya, Raul, Reasor, Kim, Rice, Gillian A. O., Rossi, Alessandro, Santos, Ricardo, Shimashita, John, Stachler, Elyse N., Stene, Lars C., Strain, Ronan, Stumpf, Rebecca, Torres, Pedro J., Twaddle, Alan, Ugochi Ibekwe, MaryAnn, Villagra, Nicolás, Wandro, Stephen, White, Bryan, Whiteley, Andy, Whiteson, Katrine L., Wijmenga, Cisca, Zambrano, Maria M., Zschach, Henrike, and Dutilh, Bas E.

Published
2019
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5. Additional file 5 of Autochthonous faecal viral transfer (FVT) impacts the murine microbiome after antibiotic perturbation

Author

Draper, Lorraine A., Ryan, Feargal J., Dalmasso, Marion, Casey, Pat G., McCann, Angela, Vimalkumar Velayudhan, R. Paul Ross, and Hill, Colin

Abstract

Additional file 5: Figure S4. qPCR was used to determine the approximate bacterial cell numbers present per gram of faeces in Study 1 (A) and Study 2 (B). Columns represent samples from individual mice (mean of four technical replicates), coloured to correspond with treatment groups as labelled on the x-axis. Results indicates that bacterial cell numbers dropped dramatically following antibiotic treatment in both studies. A One-Way ANOVA followed by Tukey test determined statistical significance; ***P value

Published
2020
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6. Additional file 1 of Autochthonous faecal viral transfer (FVT) impacts the murine microbiome after antibiotic perturbation

Author

Draper, Lorraine A., Ryan, Feargal J., Dalmasso, Marion, Casey, Pat G., McCann, Angela, Vimalkumar Velayudhan, R. Paul Ross, and Hill, Colin

Abstract

Additional file 1: Figure S1. Experimental design of Study 1 (A) and Study 2 (B). BALB/c mice (n = 16) were, after acclimatisation, administered antibiotic treatment. After a period of antibiotic wash-out the group was split into two (n = 8) and the mice were gavaged with an FVT, a sterile virome faecal filtrate (either viable or heat killed) that had been isolated from frozen faecal samples obtained from the mice during acclimatisation. In Study 2 (B) a second gavage was administered 4 days after the first, dotted vertical lines representing time points within a day. Each group of mice was individually caged. Each solid vertical line represents a day. Time points selected for sampling the faecal microbiota of each mouse in each treatment group are represented as circles and labelled. Samples were subjected to 16S rRNA sequencing and viral metagenomic sequencing.

Published
2020
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7. Additional file 6 of Autochthonous faecal viral transfer (FVT) impacts the murine microbiome after antibiotic perturbation

Author

Draper, Lorraine A., Ryan, Feargal J., Dalmasso, Marion, Casey, Pat G., McCann, Angela, Vimalkumar Velayudhan, R. Paul Ross, and Hill, Colin

Abstract

Additional file 6: Figure S5. The abundance of different taxa visualised here at the genus level for Study 1 (A) and Study 2 (B) in mice pre-treatment (Study1: S1-CT000 and S1-CT00; Study 2: S2-CT000 and S2-CT00), post-antibiotic treatment (Study 1: S1-CTAB; Study2: S2-CTAb) and over time post-gavage with either viable bacteriophage (Study 1: S1-V1 to S1-V4; Study 2: S2-V1 to S2-CeV6), or heat treated non-viable bacteriophage (Study 1: S1-C1 to S1-C4; Study 2: S2-C1 to S2-CeC6).

Published
2020
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8. Additional file 4 of Autochthonous faecal viral transfer (FVT) impacts the murine microbiome after antibiotic perturbation

Author

Draper, Lorraine A., Ryan, Feargal J., Dalmasso, Marion, Casey, Pat G., McCann, Angela, Vimalkumar Velayudhan, R. Paul Ross, and Hill, Colin

Subjects
respiratory system, human activities
Abstract

Additional file 4: Figure S3. Shannon diversity index was used to display the bacteriome alpha diversity over time for Study 1 (A) and Study 2 (B). No statistical differences were observed in alpha diversity between FVT and Control mice at corresponding time points.

Published
2020
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9. Additional file 7 of Autochthonous faecal viral transfer (FVT) impacts the murine microbiome after antibiotic perturbation

Author

Draper, Lorraine A., Ryan, Feargal J., Dalmasso, Marion, Casey, Pat G., McCann, Angela, Vimalkumar Velayudhan, R. Paul Ross, and Hill, Colin

Abstract

Additional file 7: Figure S6. The percentage relative abundance of the differentially abundant OTUs identified (via DESeq2) between FVT and Control mice are displayed to depict their relative contribution to the whole bacterial community in each cohort and in pre-antibiotic treated mice (Study1: S1-CT00 or Study 2: S2-CT00) at the timepoints indicated. OTUs that are found to be statistically different between Control mice and CT00 mice ((S1-CT00 in Study 1 or S2-CT00 Study 2) are highlighted in red text. Those that differ in their abundance to both FVT mice and CT00 mice ((S1-CT00 in Study 1 or S2-CT00 Study 2) and depicted in blue text. It appears that mice that received an FVT are more likely to maintain OTU abundances similar to their pre-treatment state.

Published
2020
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10. Additional file 3 of Autochthonous faecal viral transfer (FVT) impacts the murine microbiome after antibiotic perturbation

Author

Draper, Lorraine A., Ryan, Feargal J., Dalmasso, Marion, Casey, Pat G., McCann, Angela, Vimalkumar Velayudhan, R. Paul Ross, and Hill, Colin

Abstract

Additional file 3: Figure S2. PCoA plots compiled using Bray Curtis and Weighted Unifrac for Study 1 (A) and Study 2 (B). Statistically significant P values following UniFrac PERMANOVA analysis performed with the Adonis function to determine the statistical differences between FVT and Control mice have been inserted.

Published
2020
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12. Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Author

Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología, Edwards, Robert A., Vega, Alejandro A., Norman, Holly M., Ohaeri, Maria, Levi, Kyle, Dinsdale, Elizabeth A., Cinek, Ondrej, Aziz, Ramy K., McNair, Katelyn, Barr, Jeremy J., Bibby, Kyle, Shimashita, John, Stachler, Elyse N., Stene, Lars C., Strain, Ronan, Stumpf, Rebecca, Torres, Pedro J., Twaddle, Alan, Ugochi Ibekwe, MaryAnn, Villagra, Nicolás, Wandro, Stephen, Brouns, Stan J.J., White, Bryan, Whiteley, Andy, Whiteson, Katrine L., Wijmenga, Cisca, Zambrano, Maria M., Zschach, Henrike, Dutilh, Bas E., Cazares, Adrian, Jonge, Patrick A. de, Desnues, Christelle, Díaz Muñoz, Samuel L., Fineran, Peter C., Kurilshikov, Alexander, Lavigne, Rob, Mazankova, Karla, McCarthy, David T., Nobrega, Franklin L., Reyes Muñoz, Alejandro, Tapia, German, Trefault, Nicole, Tyakht, Alexander V., Vinuesa, Pablo, Wagemans, Jeroen, Zhernakova, Alexandra, Aarestrup, Frank M., Ahmadov, Gunduz, Alassaf, Abeer, Anton, Josefa, Asangba, Abigail, Billings, Emma K., Cantu, Vito Adrian, Carlton, Jane M., Cazares, Daniel, Cho, Gyu-Sung, Condeff, Tess, Cortés, Pilar, Cranfield, Mike, Cuevas, Daniel A., De la Iglesia, Rodrigo, Decewicz, Przemyslaw, Doane, Michael P., Dominy, Nathaniel J., Dziewit, Lukasz, Elwasila, Bashir Mukhtar, Eren, A. Murat, Franz, Charles, Fu, Jingyuan, Garcia-Aljaro, Cristina, Ghedin, Elodie, Gulino, Kristen M., Haggerty, John M., Head, Steven R., Hendriksen, Rene S., Hill, Colin, Hyöty, Heikki, Ilina, Elena N., Irwin, Mitchell T., Jeffries, Thomas C., Jofre, Juan, Junge, Randall E., Kelley, Scott T., Mirzaei, Mohammadali Khan, Kowalewski, Martin, Kumaresan, Deepak, Leigh, Steven R., Lipson, David, Lisitsyna, Eugenia S., Llagostera, Montserrat, Maritz, Julia M., Marr, Linsey C., McCann, Angela, Molshanski-Mor, Shahar, Monteiro, Silvia, Moreira-Grez, Benjamin, Morris, Megan, Mugisha, Lawrence, Muniesa, Maite, Neve, Horst, Nguyen, Nam-phuong, Nigro, Olivia D., Nilsson, Anders S., O’Connell, Taylor, Odeh, Rasha, Oliver, Andrew, Piuri, Mariana, Prussin II, Aaron J., Qimron, Udi, Quan, Zhe-Xue, Rainetova, Petra, Ramírez-Rojas, Adán, Raya, Raul, Reasor, Kim, Rice, Gillian A.O., Rossi, Alessandro, Santos, Ricardo, Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología, Edwards, Robert A., Vega, Alejandro A., Norman, Holly M., Ohaeri, Maria, Levi, Kyle, Dinsdale, Elizabeth A., Cinek, Ondrej, Aziz, Ramy K., McNair, Katelyn, Barr, Jeremy J., Bibby, Kyle, Shimashita, John, Stachler, Elyse N., Stene, Lars C., Strain, Ronan, Stumpf, Rebecca, Torres, Pedro J., Twaddle, Alan, Ugochi Ibekwe, MaryAnn, Villagra, Nicolás, Wandro, Stephen, Brouns, Stan J.J., White, Bryan, Whiteley, Andy, Whiteson, Katrine L., Wijmenga, Cisca, Zambrano, Maria M., Zschach, Henrike, Dutilh, Bas E., Cazares, Adrian, Jonge, Patrick A. de, Desnues, Christelle, Díaz Muñoz, Samuel L., Fineran, Peter C., Kurilshikov, Alexander, Lavigne, Rob, Mazankova, Karla, McCarthy, David T., Nobrega, Franklin L., Reyes Muñoz, Alejandro, Tapia, German, Trefault, Nicole, Tyakht, Alexander V., Vinuesa, Pablo, Wagemans, Jeroen, Zhernakova, Alexandra, Aarestrup, Frank M., Ahmadov, Gunduz, Alassaf, Abeer, Anton, Josefa, Asangba, Abigail, Billings, Emma K., Cantu, Vito Adrian, Carlton, Jane M., Cazares, Daniel, Cho, Gyu-Sung, Condeff, Tess, Cortés, Pilar, Cranfield, Mike, Cuevas, Daniel A., De la Iglesia, Rodrigo, Decewicz, Przemyslaw, Doane, Michael P., Dominy, Nathaniel J., Dziewit, Lukasz, Elwasila, Bashir Mukhtar, Eren, A. Murat, Franz, Charles, Fu, Jingyuan, Garcia-Aljaro, Cristina, Ghedin, Elodie, Gulino, Kristen M., Haggerty, John M., Head, Steven R., Hendriksen, Rene S., Hill, Colin, Hyöty, Heikki, Ilina, Elena N., Irwin, Mitchell T., Jeffries, Thomas C., Jofre, Juan, Junge, Randall E., Kelley, Scott T., Mirzaei, Mohammadali Khan, Kowalewski, Martin, Kumaresan, Deepak, Leigh, Steven R., Lipson, David, Lisitsyna, Eugenia S., Llagostera, Montserrat, Maritz, Julia M., Marr, Linsey C., McCann, Angela, Molshanski-Mor, Shahar, Monteiro, Silvia, Moreira-Grez, Benjamin, Morris, Megan, Mugisha, Lawrence, Muniesa, Maite, Neve, Horst, Nguyen, Nam-phuong, Nigro, Olivia D., Nilsson, Anders S., O’Connell, Taylor, Odeh, Rasha, Oliver, Andrew, Piuri, Mariana, Prussin II, Aaron J., Qimron, Udi, Quan, Zhe-Xue, Rainetova, Petra, Ramírez-Rojas, Adán, Raya, Raul, Reasor, Kim, Rice, Gillian A.O., Rossi, Alessandro, and Santos, Ricardo

Abstract

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world’s countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.

Published
2019

13. Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Author

Theoretical Biology and Bioinformatics, Sub Bioinformatics, Edwards, Robert A, Vega, Alejandro A, Norman, Holly M, Ohaeri, Maria, Levi, Kyle, Dinsdale, Elizabeth A, Cinek, Ondrej, Aziz, Ramy K, McNair, Katelyn, Barr, Jeremy J, Bibby, Kyle, Brouns, Stan J J, Cazares, Adrian, de Jonge, Patrick A, Desnues, Christelle, Díaz Muñoz, Samuel L, Fineran, Peter C, Kurilshikov, Alexander, Lavigne, Rob, Mazankova, Karla, McCarthy, David T, Nobrega, Franklin L, Reyes Muñoz, Alejandro, Tapia, German, Trefault, Nicole, Tyakht, Alexander V, Vinuesa, Pablo, Wagemans, Jeroen, Zhernakova, Alexandra, Aarestrup, Frank M, Ahmadov, Gunduz, Alassaf, Abeer, Anton, Josefa, Asangba, Abigail, Billings, Emma K, Cantu, Vito Adrian, Carlton, Jane M, Cazares, Daniel, Cho, Gyu-Sung, Condeff, Tess, Cortés, Pilar, Cranfield, Mike, Cuevas, Daniel A, De la Iglesia, Rodrigo, Decewicz, Przemyslaw, Doane, Michael P, Dominy, Nathaniel J, Dziewit, Lukasz, Elwasila, Bashir Mukhtar, Eren, A Murat, Franz, Charles, Fu, Jingyuan, Garcia-Aljaro, Cristina, Ghedin, Elodie, Gulino, Kristen M, Haggerty, John M, Head, Steven R, Hendriksen, Rene S, Hill, Colin, Hyöty, Heikki, Ilina, Elena N, Irwin, Mitchell T, Jeffries, Thomas C, Jofre, Juan, Junge, Randall E, Kelley, Scott T, Khan Mirzaei, Mohammadali, Kowalewski, Martin, Kumaresan, Deepak, Leigh, Steven R, Lipson, David, Lisitsyna, Eugenia S, Llagostera, Montserrat, Maritz, Julia M, Marr, Linsey C, McCann, Angela, Molshanski-Mor, Shahar, Monteiro, Silvia, Moreira-Grez, Benjamin, Morris, Megan, Mugisha, Lawrence, Muniesa, Maite, Neve, Horst, Nguyen, Nam-Phuong, Nigro, Olivia D, Nilsson, Anders S, O'Connell, Taylor, Odeh, Rasha, Oliver, Andrew, Piuri, Mariana, Prussin Ii, Aaron J, Qimron, Udi, Quan, Zhe-Xue, Rainetova, Petra, Ramírez-Rojas, Adán, Raya, Raul, Reasor, Kim, Rice, Gillian A O, Rossi, Alessandro, Santos, Ricardo, Shimashita, John, Stachler, Elyse N, Stene, Lars C, Strain, Ronan, Stumpf, Rebecca, Torres, Pedro J, Twaddle, Alan, Ugochi Ibekwe, MaryAnn, Villagra, Nicolás, Wandro, Stephen, White, Bryan, Whiteley, Andy, Whiteson, Katrine L, Wijmenga, Cisca, Zambrano, Maria M, Zschach, Henrike, Dutilh, Bas E, Theoretical Biology and Bioinformatics, Sub Bioinformatics, Edwards, Robert A, Vega, Alejandro A, Norman, Holly M, Ohaeri, Maria, Levi, Kyle, Dinsdale, Elizabeth A, Cinek, Ondrej, Aziz, Ramy K, McNair, Katelyn, Barr, Jeremy J, Bibby, Kyle, Brouns, Stan J J, Cazares, Adrian, de Jonge, Patrick A, Desnues, Christelle, Díaz Muñoz, Samuel L, Fineran, Peter C, Kurilshikov, Alexander, Lavigne, Rob, Mazankova, Karla, McCarthy, David T, Nobrega, Franklin L, Reyes Muñoz, Alejandro, Tapia, German, Trefault, Nicole, Tyakht, Alexander V, Vinuesa, Pablo, Wagemans, Jeroen, Zhernakova, Alexandra, Aarestrup, Frank M, Ahmadov, Gunduz, Alassaf, Abeer, Anton, Josefa, Asangba, Abigail, Billings, Emma K, Cantu, Vito Adrian, Carlton, Jane M, Cazares, Daniel, Cho, Gyu-Sung, Condeff, Tess, Cortés, Pilar, Cranfield, Mike, Cuevas, Daniel A, De la Iglesia, Rodrigo, Decewicz, Przemyslaw, Doane, Michael P, Dominy, Nathaniel J, Dziewit, Lukasz, Elwasila, Bashir Mukhtar, Eren, A Murat, Franz, Charles, Fu, Jingyuan, Garcia-Aljaro, Cristina, Ghedin, Elodie, Gulino, Kristen M, Haggerty, John M, Head, Steven R, Hendriksen, Rene S, Hill, Colin, Hyöty, Heikki, Ilina, Elena N, Irwin, Mitchell T, Jeffries, Thomas C, Jofre, Juan, Junge, Randall E, Kelley, Scott T, Khan Mirzaei, Mohammadali, Kowalewski, Martin, Kumaresan, Deepak, Leigh, Steven R, Lipson, David, Lisitsyna, Eugenia S, Llagostera, Montserrat, Maritz, Julia M, Marr, Linsey C, McCann, Angela, Molshanski-Mor, Shahar, Monteiro, Silvia, Moreira-Grez, Benjamin, Morris, Megan, Mugisha, Lawrence, Muniesa, Maite, Neve, Horst, Nguyen, Nam-Phuong, Nigro, Olivia D, Nilsson, Anders S, O'Connell, Taylor, Odeh, Rasha, Oliver, Andrew, Piuri, Mariana, Prussin Ii, Aaron J, Qimron, Udi, Quan, Zhe-Xue, Rainetova, Petra, Ramírez-Rojas, Adán, Raya, Raul, Reasor, Kim, Rice, Gillian A O, Rossi, Alessandro, Santos, Ricardo, Shimashita, John, Stachler, Elyse N, Stene, Lars C, Strain, Ronan, Stumpf, Rebecca, Torres, Pedro J, Twaddle, Alan, Ugochi Ibekwe, MaryAnn, Villagra, Nicolás, Wandro, Stephen, White, Bryan, Whiteley, Andy, Whiteson, Katrine L, Wijmenga, Cisca, Zambrano, Maria M, Zschach, Henrike, and Dutilh, Bas E

Published
2019

14. Additional file 3: of Reproducible protocols for metagenomic analysis of human faecal phageomes

Author

Shkoporov, Andrey N., Ryan, Feargal J., Draper, Lorraine A., Forde, Amanda, Stockdale, Stephen R., Daly, Karen M., McDonnell, Siobhan A., Nolan, James A., Sutton, Thomas D.S., Dalmasso, Marion, McCann, Angela, R. Paul Ross, and Hill, Colin

Abstract

Figure S1. Percentage of reads aligned to conserved segment of bacterial cpn60 gene and rRNA genes operon in virome samples from four separate experiments within this study compared to a selection of 18 total metagenomic samples sequenced as part of the Human Microbiome Project. (PDF 29 kb)

Published
2018
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15. Additional file 4: of Reproducible protocols for metagenomic analysis of human faecal phageomes

Author

Shkoporov, Andrey N., Ryan, Feargal J., Draper, Lorraine A., Forde, Amanda, Stockdale, Stephen R., Daly, Karen M., McDonnell, Siobhan A., Nolan, James A., Sutton, Thomas D.S., Dalmasso, Marion, McCann, Angela, R. Paul Ross, and Hill, Colin

Abstract

Figure S2. Effect of storage on the composition of faecal phageomes and bacteriomes (continued from Fig. 2 in the main text). A and B, α-diversity of bacterial (16S) and viral populations in faecal samples stored at two different temperatures for up to 24 h. C and D, Spearman rank ecological distances (β-diversity) between stored aliquotes of the 4 faecal samples used in the experiment, calculated for both bacterial 16S and viral datasets and visualised via non-metric multidimensional scaling (NMDS); NMDS stress values were 0.1332468 (C) and 0.09051503 (D). E and F, Barplots of relative abundance of bacterial taxonomic groups at the genus level and viruses at the individual contig level. (PDF 393 kb)

Published
2018
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16. Additional file 6: of Reproducible protocols for metagenomic analysis of human faecal phageomes

Author

Shkoporov, Andrey N., Ryan, Feargal J., Draper, Lorraine A., Forde, Amanda, Stockdale, Stephen R., Daly, Karen M., McDonnell, Siobhan A., Nolan, James A., Sutton, Thomas D.S., Dalmasso, Marion, McCann, Angela, R. Paul Ross, and Hill, Colin

Abstract

Figure S3. Effect of repeated freeze-thaw cycles on the composition of faecal phageomes and bacteriomes (continued from Fig. 3 in the main text). A and B, α-diversity of bacterial (16S) and viral populations in faecal samples subjected to up to 5 successive freeze-thaw cycles or a prolonged storage at − 80 °C. C and D, Spearman rank ecological distances (β-diversity) between aliquotes of the three faecal samples used in the freeze-thaw experiment, calculated for both bacterial 16S and viral datasets and visualised via NMDS; NMDS stress values were 9.274361e-05 (C) and 9.926038e-05 (D). E, Barplot of relative abundance of bacterial taxonomic groups at the genus level. (PDF 376 kb)

Published
2018
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18. Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Author

Edwards, Robert, primary, Vega, Alejandro, additional, Norman, Holly, additional, Ohaeri, Maria Cynthia, additional, Levi, Kyle, additional, Dinsdale, Elizabeth, additional, Cinek, Ondrej, additional, Aziz, Ramy, additional, McNair, Katelyn, additional, Barr, Jeremy, additional, Bibby, Kyle, additional, Brouns, Stan, additional, Cazares, Adrian, additional, de Jonge, Patrick A., additional, Desnues, Christelle, additional, Diaz-Munoz, Samuel, additional, Fineran, Peter, additional, Kurilshikov, Alexander, additional, Lavigne, Rob, additional, Mazankova, Karla, additional, McCarthy, David, additional, Nobrega, Franklin, additional, Reyes, Alejandro, additional, Tapia, German, additional, Trefault, Nicole, additional, Tyakht, Alexander, additional, Vinuesa, Pablo, additional, Wagemans, Jeroen, additional, Zhernakova, Alexandra, additional, Aarestrup, Frank, additional, Ahmadov, Gunduz, additional, Alassaf, Abeer, additional, Anton, Josefa, additional, Asangba, Abigail, additional, Billings, Emma, additional, Cantu, Adrian, additional, Carlton, Jane, additional, Cazares Lopez, Daniel, additional, Cho, Gyu-Sung, additional, Condeff, Tess, additional, Cortes, Pilar, additional, Cranfield, Micheal, additional, Cuevas, Daniel, additional, De la Iglesia, Rodrigo, additional, Decewicz, Przemyslaw, additional, Doane, Michael, additional, Dominy, Nathaniel, additional, Dziewit, Lukasz, additional, Elmahi, Bashir, additional, Eren, Murat, additional, Franz, Charles, additional, Fu, Jingyuan, additional, Garcia-Aljaro, Cristina, additional, Ghedin, Elodie, additional, Gulino, Kristen, additional, Haggerty, John, additional, Head, Steven, additional, Hendriksen, Rene S., additional, Hill, Colin, additional, Hyoty, Heikki, additional, Ilina, Elena, additional, Irwin, Mitchell, additional, Jeffries, Thomas, additional, Jofre, Juan, additional, Junge, Randall, additional, Kelley, Scott, additional, Kowalewski, Martin, additional, Kumaresan, Deepak, additional, Leigh, Steven, additional, Lisitsyna, Eugenia, additional, Llagostera, Montserrat, additional, Maritz, Julia M., additional, Marr, Linsey, additional, McCann, Angela, additional, Khan Mirzaei, Mohammadali, additional, Molshanski-Mor, Shahar, additional, Monteiro, Silvia, additional, Moreira-Grez, Benjamin, additional, Morris, Megan, additional, Mugisha, Lawrence, additional, Muniesa, Maite, additional, Neve, Horst, additional, Nguyen, Nam-phuong, additional, Nigro, Olivia, additional, Nilsson, Anders, additional, O'Connell, Taylor, additional, Odeh, Rasha, additional, Oliver, Andrew, additional, Piuri, Mariana, additional, Prussin, Aaron, additional, Qimron, Udi, additional, Quan, Zhe-Xue, additional, Rainetova, Petra, additional, Ramirez-Rojas, Adan, additional, Raya, Raul, additional, Rice, Gillian, additional, Rossi, Alessandro, additional, Santos, Ricardo, additional, Shimashita, John, additional, Stachler, Elyse, additional, Stene, Lars, additional, Strain, Ronan, additional, Stumpf, Rebecca, additional, Torres, Pedro, additional, Twaddle, Alan, additional, Ibekwe, Maryann Ugochi, additional, Villagra, Nicolas, additional, Wandro, Stephen, additional, White, Bryan, additional, Whiteley, Andrew, additional, Whiteson, Katrine, additional, Wijmenga, Cisca, additional, Zambrano, Maria Mercedes, additional, Zschach, Henrike, additional, and Dutilh, Bas E., additional

Published
2019
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19. The tree of genomes: An empirical comparison of genome-phylogeny reconstruction methods

Author

McInerney James O, Cotton James A, and McCann Angela

Subjects
Evolution, QH359-425
Abstract

Abstract Background In the past decade or more, the emphasis for reconstructing species phylogenies has moved from the analysis of a single gene to the analysis of multiple genes and even completed genomes. The simplest method of scaling up is to use familiar analysis methods on a larger scale and this is the most popular approach. However, duplications and losses of genes along with horizontal gene transfer (HGT) can lead to a situation where there is only an indirect relationship between gene and genome phylogenies. In this study we examine five widely-used approaches and their variants to see if indeed they are more-or-less saying the same thing. In particular, we focus on Conditioned Reconstruction as it is a method that is designed to work well even if HGT is present. Results We confirm a previous suggestion that this method has a systematic bias. We show that no two methods produce the same results and most current methods of inferring genome phylogenies produce results that are significantly different to other methods. Conclusion We conclude that genome phylogenies need to be interpreted differently, depending on the method used to construct them.

Published
2008
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20. Functional metagenomic profiling of the intestinal microbiome in subjects consuming omnivore, ovo-lacto-vegetarian and vegan diets

Author

Ferrocino, Ilario, McCann, Angela, Di Cagno, Raffaella, Turroni, Silvia, Neviani, Erasmo, De Angelis, Maria, Ercolini, Danilo, O’Toole, Paul W., Cocolin, Luca, DE FILIPPIS, FRANCESCA, European Molecular Biology Laboratory, Ferrocino, Ilario, DE FILIPPIS, Francesca, Mccann, Angela, Di Cagno, Raffaella, Turroni, Silvia, Neviani, Erasmo, De Angelis, Maria, Ercolini, Danilo, O’Toole, Paul W., and Cocolin, Luca

Published
2015

21. Gut microbiota and metagenomic diversity of omnivore, vegetarian and vegan healthy subject

Author

Ferrocino, Ilario, McCann, Angela, Di Cagno, Raffaella, Turroni, Silvia, Neviani, Erasmo, De Angelis, Maria, Ercolini, Danilo, O’Toole, Paul W., Cocolin, Luca, DE FILIPPIS, FRANCESCA, 3rd International Conference on Microbial Diversity 2015 Organizing Committee, Ferrocino, Ilario, DE FILIPPIS, Francesca, Mccann, Angela, Di Cagno, Raffaella, Turroni, Silvia, Neviani, Erasmo, De Angelis, Maria, Ercolini, Danilo, O’Toole, Paul W., and Cocolin, Luca

Published
2015

27. Viromes of one year old infants reveal the impact of birth mode on micro biomediversity.

Author

McCann, Angela, Ryan, Feargal J., Stockdale, Stephen R., Dalmasso, Marion, Blake, Tony, Anthony Ryan, C., Stanton, Catherine, Mills, Susan, Ross, Paul R., and Hill, Colin

Subjects
INFANTS, CHILDBIRTH, CESAREAN section, BACTERIAL diversity, MOTHER-child relationship
Abstract

Establishing a diverse gut microbiota after birth is being increasingly recognised as important for preventing illnesses later in life. It is well established that bacterial diversity rapidly increases post-partum; however, few studies have examined the infant gut virome/phageome during this developmental period. We performed a metagenomic analysis of 20 infant faecal viromes at one year of age to determine whether spontaneous vaginal delivery (SVD) or caesarean section (CS) influenced viral composition. We find that birth mode results in distinctly different viral communities, with SVD infants having greater viral and bacteriophage diversity. We demonstrate that CrAssphage is acquired early in life, both in this cohort and two others, although no difference in birth mode is detected. A previous study has shown that bacterial OTU’s (operational taxonomic units) identified in the same infants could not discriminate between birth mode at 12 months of age. Therefore, our results indicate that vertical transmission of viral communities from mother to child may play a role in shaping the early life microbiome, and that birth mode should be considered when studying the early life gut virome. [ABSTRACT FROM AUTHOR]

Published
2019
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28. Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera

Author

SFI, ERC, US National Institute of Dental and Craniofacial Research, National Natural Science Foundation of China, Academy of Finland, Sun, Zhihong, Harris, Hugh M. B., McCann, Angela, Guo, Chenyi, Argimon, Silvia, Zhang, Wenyi, Yang, Xianwei, Jeffrey, Ian B., Cooney, Jakki C., Kagawa, Todd F., Liu, Wenjun, Song, Yuqin, Salvetti, Elisa, Wrobel, Agneszka, Rasinkangas, Pia, Parkhill, Julian, Rea, Mary C., O'Sullivan, Orla, Ritari, Jarmo, Douillard, Francois P., Ross, Paul R., Yang, Ruifu, Briner, Alexandra E., Felis, Giovanna E., de Vos, Willem M., Barrangou, Rodolphe, Klaenhammer, Todd R., Caufield, Page W., Cui, Yujun, Zhang, Heping, O'Toole, Paul W., SFI, ERC, US National Institute of Dental and Craniofacial Research, National Natural Science Foundation of China, Academy of Finland, Sun, Zhihong, Harris, Hugh M. B., McCann, Angela, Guo, Chenyi, Argimon, Silvia, Zhang, Wenyi, Yang, Xianwei, Jeffrey, Ian B., Cooney, Jakki C., Kagawa, Todd F., Liu, Wenjun, Song, Yuqin, Salvetti, Elisa, Wrobel, Agneszka, Rasinkangas, Pia, Parkhill, Julian, Rea, Mary C., O'Sullivan, Orla, Ritari, Jarmo, Douillard, Francois P., Ross, Paul R., Yang, Ruifu, Briner, Alexandra E., Felis, Giovanna E., de Vos, Willem M., Barrangou, Rodolphe, Klaenhammer, Todd R., Caufield, Page W., Cui, Yujun, Zhang, Heping, and O'Toole, Paul W.

Abstract

peer-reviewed, Lactobacilli are a diverse group of species that occupy diverse nutrient-rich niches associated with humans, animals, plants and food. They are used widely in biotechnology and food preservation, and are being explored as therapeutics. Exploiting lactobacilli has been complicated by metabolic diversity, unclear species identity and uncertain relationships between them and other commercially important lactic acid bacteria. The capacity for biotransformations catalysed by lactobacilli is an untapped biotechnology resource. Here we report the genome sequences of 213 Lactobacillus strains and associated genera, and their encoded genetic catalogue for modifying carbohydrates and proteins. In addition, we describe broad and diverse presence of novel CRISPR-Cas immune systems in lactobacilli that may be exploited for genome editing. We rationalize the phylogenomic distribution of host interaction factors and bacteriocins that affect their natural and industrial environments, and mechanisms to withstand stress during technological processes. We present a robust phylogenomic framework of existing species and for classifying new species., PUBLISHED, peer-reviewed

Published
2016

29. Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera

Author

Sun, Zhihong, primary, Harris, Hugh M. B., additional, McCann, Angela, additional, Guo, Chenyi, additional, Argimón, Silvia, additional, Zhang, Wenyi, additional, Yang, Xianwei, additional, Jeffery, Ian B, additional, Cooney, Jakki C., additional, Kagawa, Todd F., additional, Liu, Wenjun, additional, Song, Yuqin, additional, Salvetti, Elisa, additional, Wrobel, Agnieszka, additional, Rasinkangas, Pia, additional, Parkhill, Julian, additional, Rea, Mary C., additional, O’Sullivan, Orla, additional, Ritari, Jarmo, additional, Douillard, François P., additional, Paul Ross, R., additional, Yang, Ruifu, additional, Briner, Alexandra E., additional, Felis, Giovanna E., additional, de Vos, Willem M., additional, Barrangou, Rodolphe, additional, Klaenhammer, Todd R., additional, Caufield, Page W., additional, Cui, Yujun, additional, Zhang, Heping, additional, and O’Toole, Paul W., additional

Published
2015
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31. Detection and Genomic Characterization of Motility in Lactobacillus curvatus: Confirmation of Motility in a Species outside the Lactobacillus salivarius Clade

Author

Cousin, Fabien J., primary, Lynch, Shónagh M., additional, Harris, Hugh M. B., additional, McCann, Angela, additional, Lynch, Denise B., additional, Neville, B. Anne, additional, Irisawa, Tomohiro, additional, Okada, Sanae, additional, Endo, Akihito, additional, and O'Toole, Paul W., additional

Published
2015
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32. Archaea Appear to Dominate the Microbiome of Inflatella pellicula Deep Sea Sponges

Author

Jackson, Stephen, Flemer, Burkhardt, McCann, Angela, Kennedy, Jonathan, Morrissey, John, O'Gara, Fergal, Dobson, Alan, Jackson, Stephen, Flemer, Burkhardt, McCann, Angela, Kennedy, Jonathan, Morrissey, John, O'Gara, Fergal, and Dobson, Alan

Abstract

Microbes associated with marine sponges play significant roles in host physiology. Remarkable levels of microbial diversity have been observed in sponges worldwide through both culture-dependent and culture-independent studies. Most studies have focused on the structure of the bacterial communities in sponges and have involved sponges sampled from shallow waters. Here, we used pyrosequencing of 16S rRNA genes to compare the bacterial and archaeal communities associated with two individuals of the marine sponge Inflatella pellicula from the deep-sea, sampled from a depth of 2,900 m, a depth which far exceeds any previous sequence-based report of sponge-associated microbial communities. Sponge-microbial communities were also compared to the microbial community in the surrounding seawater. Sponge-associated microbial communities were dominated by archaeal sequencing reads with a single archaeal OTU, comprising ~60% and ~72% of sequences, being observed from Inflatella pellicula. Archaeal sequencing reads were less abundant in seawater (~11% of sequences). Sponge-associated microbial communities were less diverse and less even than any other sponge-microbial community investigated to date with just 210 and 273 OTUs (97% sequence identity) identified in sponges, with 4 and 6 dominant OTUs comprising ~88% and ~89% of sequences, respectively. Members of the candidate phyla, SAR406, NC10 and ZB3 are reported here from sponges for the first time, increasing the number of bacterial phyla or candidate divisions associated with sponges to 43. A minor cohort from both sponge samples (~0.2% and ~0.3% of sequences) were not classified to phylum level. A single OTU, common to both sponge individuals, dominates these unclassified reads and shares sequence homology with a sponge associated clone which itself has no known close relative and may represent a novel taxon.

Published
2013

34. The tree of genomes: An empirical comparison of genome-phylogeny reconstruction methods

Author

McCann, Angela, Cotton, James A., McInerney, James O., McCann, Angela, Cotton, James A., and McInerney, James O.

Abstract

Background: In the past decade or more, the emphasis for reconstructing species phylogenies has moved from the analysis of a single gene to the analysis of multiple genes and even completed genomes. The simplest method of scaling up is to use familiar analysis methods on a larger scale and this is the most popular approach. However, duplications and losses of genes along with horizontal gene transfer (HGT) can lead to a situation where there is only an indirect relationship between gene and genome phylogenies. In this study we examine five widely-used approaches and their variants to see if indeed they are more-or-less saying the same thing. In particular, we focus on Conditioned Reconstruction as it is a method that is designed to work well even if HGT is present. Results: We confirm a previous suggestion that this method has a systematic bias. We show that no two methods produce the same results and most current methods of inferring genome phylogenies produce results that are significantly different to other methods. Conclusion: We conclude that genome phylogenies need to be interpreted differently, depending on the method used to construct them.

Published
2008

36. A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic

Author

Holden, Matthew T.G., primary, Hsu, Li-Yang, additional, Kurt, Kevin, additional, Weinert, Lucy A., additional, Mather, Alison E., additional, Harris, Simon R., additional, Strommenger, Birgit, additional, Layer, Franziska, additional, Witte, Wolfgang, additional, de Lencastre, Herminia, additional, Skov, Robert, additional, Westh, Henrik, additional, Žemličková, Helena, additional, Coombs, Geoffrey, additional, Kearns, Angela M., additional, Hill, Robert L.R., additional, Edgeworth, Jonathan, additional, Gould, Ian, additional, Gant, Vanya, additional, Cooke, Jonathan, additional, Edwards, Giles F., additional, McAdam, Paul R., additional, Templeton, Kate E., additional, McCann, Angela, additional, Zhou, Zhemin, additional, Castillo-Ramírez, Santiago, additional, Feil, Edward J., additional, Hudson, Lyndsey O., additional, Enright, Mark C., additional, Balloux, Francois, additional, Aanensen, David M., additional, Spratt, Brian G., additional, Fitzgerald, J. Ross, additional, Parkhill, Julian, additional, Achtman, Mark, additional, Bentley, Stephen D., additional, and Nübel, Ulrich, additional

Published
2013
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38. Transient Darwinian selection in Salmonella enterica serovar Paratyphi A during 450 years of global spread of enteric fever.

Author

Zhemin Zhou, McCann, Angela, Weill, François-Xavier, Blin, Camille, Nair, Satheesh, Wain, John, Dougan, Gordon, and Achtman, Mark

Subjects
*SALMONELLA, *BODY temperature, *TYPHOID fever, *EXANTHEMA, *EPIDEMIOLOGY
Abstract

Multiple epidemic diseases have been designated as emerging or reemerging because the numbers of clinical cases have increased. Emerging diseases are often suspected to be driven by increased virulence or fitness, possibly associated with the gain of novel genes or mutations. However, the time period over which humans have been afflicted by such diseases is only known for very few bacterial pathogens, and the evidence for recently increased virulence or fitness is scanty. Has Darwinian (diversifying) selection at the genomic level recently driven microevolution within bacterial pathogens of humans? Salmonella enterica serovar Paratyphi A is a major cause of enteric fever, with a microbiological history dating to 1898. We identified seven modern lineages among 149 genomes on the basis of 4,584 SNPs in the core genome and estimated that Paratyphi A originated 450 y ago. During that time period, the effective population size has undergone expansion, reduction, and recent expansion. Mutations, some of which inactivate genes, have occurred continuously over the history of Paratyphi A, as has the gain or loss of accessory genes. We also identified 273 mutations that were under Darwinian selection. However, most genetic changes are transient, continuously being removed by purifying selection, and the genome of Paratyphi A has not changed dramatically over centuries. We conclude that Darwinian selection is not responsible for increased frequency of enteric fever and suggest that environmental changes may be more important for the frequency of disease. [ABSTRACT FROM AUTHOR]

Published
2014
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39. Archaea Appear to Dominate the Microbiome of Inflatella pellicula Deep Sea Sponges.

Author

Jackson, Stephen A., Flemer, Burkhardt, McCann, Angela, Kennedy, Jonathan, Morrissey, John P., O’Gara, Fergal, and Dobson, Alan D. W.

Subjects
ARCHAEBACTERIA, MICROBIOLOGY, RIBOSOMAL RNA, MICROBIAL diversity, INVERTEBRATE sponge physiology, MICROBIAL cultures, WATER depth
Abstract

Microbes associated with marine sponges play significant roles in host physiology. Remarkable levels of microbial diversity have been observed in sponges worldwide through both culture-dependent and culture-independent studies. Most studies have focused on the structure of the bacterial communities in sponges and have involved sponges sampled from shallow waters. Here, we used pyrosequencing of 16S rRNA genes to compare the bacterial and archaeal communities associated with two individuals of the marine sponge Inflatella pellicula from the deep-sea, sampled from a depth of 2,900 m, a depth which far exceeds any previous sequence-based report of sponge-associated microbial communities. Sponge-microbial communities were also compared to the microbial community in the surrounding seawater. Sponge-associated microbial communities were dominated by archaeal sequencing reads with a single archaeal OTU, comprising ∼60% and ∼72% of sequences, being observed from Inflatella pellicula. Archaeal sequencing reads were less abundant in seawater (∼11% of sequences). Sponge-associated microbial communities were less diverse and less even than any other sponge-microbial community investigated to date with just 210 and 273 OTUs (97% sequence identity) identified in sponges, with 4 and 6 dominant OTUs comprising ∼88% and ∼89% of sequences, respectively. Members of the candidate phyla, SAR406, NC10 and ZB3 are reported here from sponges for the first time, increasing the number of bacterial phyla or candidate divisions associated with sponges to 43. A minor cohort from both sponge samples (∼0.2% and ∼0.3% of sequences) were not classified to phylum level. A single OTU, common to both sponge individuals, dominates these unclassified reads and shares sequence homology with a sponge associated clone which itself has no known close relative and may represent a novel taxon. [ABSTRACT FROM AUTHOR]

Published
2013
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40. Improving market for finance talent

Author

McCann, Angela

Subjects
Financial services industry -- Planning, Financial services industry -- Recruiting, Accountants -- Forecasts and trends, Accountants -- Employment, Financial services industry, Company business planning, Industry hiring, Market trend/market analysis, Banking, finance and accounting industries, Business
Abstract

The demand for finance professionals in 2010 has much improved compared to 2009 wherein the early part saw small demand for financial talents as banks restructured. Most financial services plan to make important strategic hires to enhance controls, boost visibility and cope with the change in volume business. Insights on skills that are on great demand are also given.

Published
2010

41. Neutral Genomic Microevolution of a Recently Emerged Pathogen, Salmonella enterica Serovar Agona.

Author

Zhemin Zhou, McCann, Angela, Litrup, Eva, Murphy, Ronan, Cormican, Martin, Fanning, Seamus, Brown, Derek, Guttman, David S., Brisse, Sylvain, and Achtman, Mark

Subjects
*SALMONELLA enterica, *GASTROENTERITIS, *GENOMES, *GENOMICS, *FOOD poisoning, *ELECTROPHORESIS
Abstract

Salmonella enterica serovar Agona has caused multiple food-borne outbreaks of gastroenteritis since it was first isolated in 1952. We analyzed the genomes of 73 isolates from global sources, comparing five distinct outbreaks with sporadic infections as well as food contamination and the environment. Agona consists of three lineages with minimal mutational diversity: only 846 single nucleotide polymorphisms (SNPs) have accumulated in the non-repetitive, core genome since Agona evolved in 1932 and subsequently underwent a major population expansion in the 1960s. Homologous recombination with other serovars of S. enterica imported 42 recombinational tracts (360 kb) in 5/143 nodes within the genealogy, which resulted in 3,164 additional SNPs. In contrast to this paucity of genetic diversity, Agona is highly diverse according to pulsed-field gel electrophoresis (PFGE), which is used to assign isolates to outbreaks. PFGE diversity reflects a highly dynamic accessory genome associated with the gain or loss (indels) of 51 bacteriophages, 10 plasmids, and 6 integrative conjugational elements (ICE/IMEs), but did not correlate uniquely with outbreaks. Unlike the core genome, indels occurred repeatedly in independent nodes (homoplasies), resulting in inaccurate PFGE genealogies. The accessory genome contained only few cargo genes relevant to infection, other than antibiotic resistance. Thus, most of the genetic diversity within this recently emerged pathogen reflects changes in the accessory genome, or is due to recombination, but these changes seemed to reflect neutral processes rather than Darwinian selection. Each outbreak was caused by an independent clade, without universal, outbreak-associated genomic features, and none of the variable genes in the pan-genome seemed to be associated with an ability to cause outbreaks. [ABSTRACT FROM AUTHOR]

Published
2013
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42. Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults

Author

US Allen Foundation, Institute Research Measure, The Irish Heart Foundation, SFI, McCann, Angela, Jeffery, Ian B., Ouliass, Bouchra, Ferland, Guylaine, Fu, Xueyen, Booth, Sarah L, Tran, Tam T.T., O’Toole, Paul W, O'Connor, Eibhlís M., US Allen Foundation, Institute Research Measure, The Irish Heart Foundation, SFI, McCann, Angela, Jeffery, Ian B., Ouliass, Bouchra, Ferland, Guylaine, Fu, Xueyen, Booth, Sarah L, Tran, Tam T.T., O’Toole, Paul W, and O'Connor, Eibhlís M.

Abstract

peer-reviewed, ackground: Vitamin K has multiple important physiological roles, including blood coagulation and beneficial effects on myelin integrity in the brain. Some intestinal microbes possess the genes to produce vitamin K in the form of menaquinone (MK). MK appears in higher concentration in tissues, such as the brain, particularly MK4, than the dietary form of phylloquinone (PK). Lower PK concentrations have been reported in patients with Alzheimer disease while higher serum PK concentrations have been positively associated with verbal episodic memory. Despite knowledge of the importance of vitamin K for various health parameters, few studies have measured MK concentration and biosynthesis by gut commensals. Objective: The aim of the current study was to investigate the relation between genes involved in gut-microbiota derived MK, concentrations of MK isoforms, and cognitive function. Methods: Shotgun metagenomic sequencing of the gut microbiome of 74 elderly individuals with different cognitive ability levels was performed. From this, gene counts for microbial MK biosynthesis were determined. Associations between clusters of individuals, grouped based on a similar presence and prevalence of MK biosynthesis genes, and cognitive ability were investigated. Fecal MK concentrations were quantified by HPLC to investigate correlations with subject clusters. Results: Separation of subject groups defined by banded quantification of the genetic potential of their microbiome to biosynthesize MK was associated with significant differences in cognitive ability [assessed using theMini-Mental State Examination (MMSE)]. Three MK isoforms were found to be positively associated with MMSE, along with the identification of key components of the MK pathway that drive this association. Although the causality and direction of these associations remain unknown, these findings justify further studies. Conclusions: This study provides evidence that although total concentrations of MK did not covar

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