# Genome-centric investigation of bile acid metabolizing microbiota of dairy cows and associated diet-induced functional implications

**Authors:** Limei Lin, Zheng Lai, Huisheng Yang, Jiyou Zhang, Weibiao Qi, Fei Xie, Shengyong Mao

PMC · DOI: 10.1038/s41396-022-01333-5 · 2022-10-19

## TL;DR

This study explores how gut microbes in dairy cows process bile acids and how diet affects these processes, offering insights for improving cow health.

## Contribution

The first genome-centric analysis of bile acid metabolism in dairy cows using metagenomics and metabolomics.

## Key findings

- 372 high-quality MAGs were identified involved in bile acid metabolism in dairy cow intestines.
- BSH homologs were grouped into 12 clusters with distinct evolutionary and ecological traits.
- Firmicutes bacterium CAG-110 was linked to changes in bile acid levels and intestinal inflammation after dietary shifts.

## Abstract

Although the importance of bile acid (BA)-related microbial strains and enzymes is increasingly recognized for monogastric animals, a lack of knowledge about BA metabolism in dairy cows limits functional applications aimed at the targeted modulation of microbe–host interactions for animal production and health. In the present study, 108 content samples from six intestinal regions of dairy cows were used for shotgun metagenomic sequencing. Overall, 372 high-quality metagenome-assembled genomes (MAGs) were involved in BA deconjugation, oxidation, and dehydroxylation pathways. Furthermore, the BA-metabolizing microbiome predominately occurred in the large intestine, resulting in the accumulation of secondary unconjugated BAs. Comparative genomic analysis revealed that the bile salt hydrolase (BSH)-carrying microbial populations managed with the selective environment of the dairy cow intestine by adopting numerous host mucin glycan-degrading abilities. A sequence similarity network analysis classified 439 BSH homologs into 12 clusters and identified different clusters with diverse evolution, taxonomy, signal peptides, and ecological niches. Our omics data further revealed that the strains of Firmicutes bacterium CAG-110 processed the increased abundance of BSHs from Cluster 1, coinciding with the changes in the colon cholic acid concentration after grain introduction, and were intricately related to intestinal inflammation. This study is the first to use a genome-centric approach and whole intestine-targeted metabolomics to reveal microbial BA metabolism and its diet-induced functional implications in dairy cows. These findings provide insight into the manipulation of intestinal microorganisms for improving host health.

## Linked entities

- **Genes:** bsh (brain-specific homeobox) [NCBI Gene 35266]
- **Chemicals:** bile acid (PubChem CID 439520), cholic acid (PubChem CID 221493)
- **Species:** Firmicutes bacterium CAG:110 (taxon 1263000)

## Full-text entities

- **Genes:** SAA2 (serum amyloid A2) [NCBI Gene 506412] {aka SAA, SAA1}, MBL2 (mannose binding lectin 2) [NCBI Gene 281297] {aka MBL}, IDUA (alpha-L-iduronidase) [NCBI Gene 511050], CHGA (chromogranin A) [NCBI Gene 281070], HP (haptoglobin) [NCBI Gene 280692], LBP (lipopolysaccharide binding protein) [NCBI Gene 512242], TPM1 (tropomyosin 1) [NCBI Gene 281544], C8B (complement C8 beta chain) [NCBI Gene 513217], C8A (complement C8 alpha chain) [NCBI Gene 527391], CR2 (complement C3d receptor 2) [NCBI Gene 407126] {aka cd21}, AHSG (alpha 2-HS glycoprotein) [NCBI Gene 280988], MAG (myelin associated glycoprotein) [NCBI Gene 540576], NAGA (alpha-N-acetylgalactosaminidase) [NCBI Gene 533357], SAA4 (serum amyloid A4, constitutive) [NCBI Gene 505308], LOC781146 (lysozyme) [NCBI Gene 781146], SERPINF2 (serpin family F member 2) [NCBI Gene 282522] {aka PLI}, ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) [NCBI Gene 513700], MUC1 (mucin 1, cell surface associated) [NCBI Gene 281333] {aka mucin}, MBL1 (mannose binding lectin 1) [NCBI Gene 497014] {aka MBL-A, MBLA}, C4BPB (complement component 4 binding protein beta) [NCBI Gene 281652]
- **Diseases:** metabolic diseases (MESH:D008659), cancer (MESH:D009369), colitis (MESH:D003092), inflammation (MESH:D007249), BSH (MESH:D013651)
- **Chemicals:** glycochenodeoxycholic acid (MESH:D005999), lactose (MESH:D007785), starch (MESH:D013213), BA (MESH:D001464), propionate (MESH:D011422), paraformaldehyde (MESH:C003043), glucose (MESH:D005947), TCA (MESH:D014238), Fat (MESH:D005223), glycocholic acid (MESH:D006000), lactate (MESH:D019344), carbohydrate (MESH:D002241), NAD(P)+ (MESH:D009249), Steroid hormone (MESH:D013256), 5,10-methylenetetrahydrofolate (MESH:C013123), VFAs (MESH:D005232), glycan (MESH:D011134), Cholesterol (MESH:D002784), butyrate (MESH:D002087), lipopolysaccharides (MESH:D008070), sialic acid (MESH:D019158), taurine (MESH:D013654), cellulose (MESH:D002482), BA (MESH:D001647), glycodeoxycholic acid (MESH:D006002), sugars (MESH:D000073893), Octopamine (MESH:D009655), cholic acid (MESH:D019826), BSH (MESH:C014651), methanol (MESH:D000432), oxygen (MESH:D010100), salt (MESH:D012492), taurolithocholic acid (MESH:D013658), water (MESH:D014867), Sec (MESH:D017279), ATP (MESH:D000255), CoA (MESH:D003065), nitrogen (MESH:D009584), acetyl-CoA (MESH:D000105), TRIzol (MESH:C411644), Formate (MESH:C030544), Arachidonic acid (MESH:D016718), glycolithocholic acid (MESH:C027746), fucose (MESH:D005643), 3-DHCA (-), agarose (MESH:D012685), Linoleic acid (MESH:D019787), mannose (MESH:D008358), taurocholic acid (MESH:D013656), CA (MESH:D002118), taurodeoxycholic acid (MESH:D013657), hydroxysteroids (MESH:D006914), valerate (MESH:D014631), Thiamine (MESH:D013831), xylans (MESH:D014990), 23-nordeoxycholic acid (MESH:C033582), acetonitrile (MESH:C032159), thiamine diphosphate (MESH:D013835), taurochenodeoxycholate (MESH:D013655), pyruvate (MESH:D019289)
- **Species:** Yoonia sp. (species) [taxon 2212373], Sus scrofa (pig, species) [taxon 9823], Homo sapiens (human, species) [taxon 9606], Bacillota bacterium (species) [taxon 1879010], Alistipes (genus) [taxon 239759], Bos taurus (bovine, species) [taxon 9913], Bifidobacterium pseudolongum subsp. globosum (subspecies) [taxon 1690], Bacteroidales (order) [taxon 171549], Ruminococcus (genus) [taxon 1263], Firmicutes bacterium CAG:110 (species) [taxon 1263000], Methanobacteria (class) [taxon 183925], Mus musculus (house mouse, species) [taxon 10090], metagenome (species) [taxon 256318]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), DUO — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_C0XV)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9750977/full.md

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Source: https://tomesphere.com/paper/PMC9750977