11. Butyric
acid
Ben Mills,
https://commons.wikimedia.org/
Produced by many (…all?) Lachnospiraceae
- Important energy source. Thanks, microbiome!
- Potential regulator of mucosal gene expression
- Protective against some diseases (e.g. colitis)
- Inhibitor of cancer cell proliferation?
- Suppressor of C. difficile
12. Taxonomy, phylogeny
(16S and so on)
Function (genomes,
metagenomes)
Ecology (distribution)
http://bighugelabs.com/badge.php
Image: http://ijsb.sgmjournals.org/content/53/1/201/F3.expansion
An identity for
Lachnospiraceae?
Does everyone play the same ecological role (e.g., butyrate production?)
What sort of habitat differentiation exists in the group?
What is their relationship with other groups in the gut and elsewhere?
18. Why the disagreement?
• Is 16S wrong?
• Low support values at some nodes
• Is concatenation wrong?
• Most individual gene trees reject the concatenated AND
16S phylogenies
• A mess due to lateral gene transfer?
19. In search of ecological identity
• Is it butyrate production? Probably NO
Catonella morbi ATCC 51271
Cellulosilyticum lentocellum DSM 5427
Dorea formicigenerans ATCC 27755
Dorea longicatena DSM 13814
Lachnospiraceae bacterium 1_1_57FAA
Lachnospiraceae bacterium 2_1_46FAA
Lachnospiraceae bacterium 2_1_58FAA
Lachnospiraceae bacterium 3_1_46FAA
Lachnospiraceae bacterium 4_1_37FAA
Lachnospiraceae bacterium 5_1_57FAA
Lachnospiraceae bacterium 6_1_63FAA
Lachnospiraceae bacterium 8_1_57FAA
Lachnospiraceae bacterium 9_1_43BFAA
Marvinbryantia formatexigens DSM 14469
Oribacterium sinus F0268
Oribacterium sp. oral taxon 078 str. F0262
Oribacterium sp. oral taxon 108 str. F0425
Coprococcus eutactus ATCC 27759
Butyrivibrio crossotus DSM 2876
Butyrivibrio proteoclasticus B316
Coprococcus comes ATCC 27758
Lachnospiraceae bacterium 1_4_56FAA
Lachnospiraceae bacterium 3_1_57FAA_CT1
Shuttleworthia satelles DSM 14600
Anaerostipes caccae DSM 14662
Anaerostipes sp. 3_2_56FAA
Lachnospiraceae bacterium 5_1_63FAA
Lachnospiraceae oral taxon 107 str. F0167
Roseburia intestinalis L1-82
Roseburia inulinivorans DSM 16841
Showing 1 or 2 of the 3
known pathways
Showing 0 of the 3
known pathways
20. Butyric acid production:
three different ways,
and
a phylogenetic mess
Roseburia-type butyryl-CoA:acetate CoA-transferase
butyryl-CoA:acetate CoA-transferase
Butyrate kinase
21. Gut-associated versus everyone else:
2 x sigma factor, 6 x sporulation protein, cell wall
hydrolase (22/1)
3 x sporulation protein (22/0)
Others:
- penicillin-binding protein
- Antimicrobial extrusion protein
- Signal transduction / two-component regulators
- …
In search of ecological identity
II
22. Spo gene trees are largely consistent with one another
Spo sigma factors present in all genomes
– suggestive of LOSS in oral + rumen genomes
SpoIVA –
sine qua non
24. Mostly mammals: a
Lachnospiraceae Love Story
• Drop acid
• Butyrate production is readily gained and lost (as you
might expect)
• Lose your coat
• The capacity for spore production has been lost several
times
• Leave in someone else’s genes
• LGT has clearly impacted the group in a big way (to be
continued…)
25. What next?
• Environmental distribution of different Lachno
groups
• Different abundances in healthy vs. diseased?
• Pathway-level analysis of butyrate vs. non-butyrate-
producing strains
• Non-butyrate are enriched for a couple of
“pathogenesis” genes, but nothing compelling yet
• Interesting split in the gut-associated strains
• Detailed profiling of LGT in the group
• New data that we cannot generate ourselves
• Transcriptomics!!