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Host–gut microbiota–bile acid axis integrates dietary starch to regulate milk fatty acid metabolism in dairy goats

ABSTRACT:

Bile acids (BA) and BA-related microbiota are essential for ruminant lipid metabolism, yet targeted modulation to enhance production and health remain underexplored. Herein, we investigated the interplay between dietary rumen degradable starch, BA metabolism, and milk fatty acids (FAs) synthesis in dairy goats using a multi-omics approach. Lactating dairy goats of comparable milk yield and body weight were allocated to dietary treatments differing in rumen degradable starch to evaluate impacts on milk FAs profiles, gut BA metabolism, and gut microbiota. Additional BA supplementation was applied to assess its potential to mitigate high rumen degradable-rate starch (HRDS)-induced alterations, with targeted tissue sampling to investigate microbe–host interactions. Goats fed the HRDS diet exhibited significant lower milk FAs concentration and yield compared to those on LRDS. Targeted metabolomic analyses revealed that the HRDS diet led to marked deficiencies in five key small intestine BA-cholic acid, chenodeoxycholic acid, lithocholic acid, hyocholic acid, and hyodeoxycholic acid. Macrogenomic sequencing identified Clostridium and Turicibacter as key microbial drivers involved in primary (ko00120) and secondary (ko00121) BA metabolism, with significant downregulation of 7α-hydroxysteroid dehydrogenase (7α-HSDH) in the HRDS group. BA supplementation restored both milk FAs concentration and yield. Additionally, HRDS reduced small intestine FAs concentration and decreased the abundance of Oscillospiraceae_bacterium, a taxon positively correlated with small intestine FAs concentration. Taurine-conjugated bile acids were found to mediate this effect. BA supplementation enhanced BA metabolism and increased activities of bile salt hydrolases and 7α-HSDH in the small intestine, and upregulation host FAs degradation and uptake responses, notably through increased FA binding protein 6 expression. In conclusion, our comprehensive investigation into the interplay between diets, gut microbes, and BA sheds light on the intricate mechanisms regulating milk FAs synthesis in dairy goats.

INSTRUMENT(S): Liquid Chromatography MS - alternating

PROVIDER: MTBLS13483 | MetaboLights | 2025-12-09

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13483_LC-MS_alternating__metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13483_LC-MS___metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13483_LC-MS_alternating__metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS13483 .txt	Txt

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Project description:In dairy cows, administration of high dosages of niacin (NA) was found to cause anti-lipolytic effects, which are mediated by the NA receptor hydroxyl-carboxylic acid receptor 2 (HCAR2) in white adipose tissue (WAT), and thereby to an altered hepatic lipid metabolism. However, almost no attention has been paid to possible direct effects of NA in cattle liver, despite showing that HCAR2 is expressed also in the liver of cattle and is even more abundant than in WAT. Due to this, we hypothesized that feeding of rumen-protected NA to dairy cows influences critical metabolic and/or signaling pathways in the liver through inducing changes in the hepatic transcriptome. In order to identify these pathways, we applied genome-wide transcript profiling in liver biopsies obtained at 1 wk postpartum (p.p.) from dairy cows of a recent study (Zeitz et al., 2018) which were fed a total mixed ration without (control group) or with rumen-protected NA from 21 d before calving until 3 wk p.p. Hepatic transcript profiling revealed that a total of 487 transcripts were differentially expressed [filter criteria fold change (FC) > 1.2 or FC < -1.2 and P < 0.05] in the liver at 1 wk p.p. between cows fed NA and control cows. Substantially more transcripts were down-regulated (n = 338), while only 149 transcripts were up-regulated by NA in the liver of cows. Gene set enrichment analysis (GSEA) for the up-regulated transcripts revealed that the most enriched gene ontology (GO) biological process terms were exclusively related to immune processes, such as leukocyte differentiation, immune system process, leukocyte differentiation, activation of immune response and acute inflammatory response. In line with this, the plasma concentration of the acute phase protein haptoglobin tended to be increased in dairy cows fed rumen-protected NA compared to control cows (P < 0.1). GSEA of the down-regulated transcripts showed that the most enriched biological process terms were related to metabolic processes, such as cellular metabolic process, small molecule metabolic process, lipid catabolic process, organic cyclic compound metabolic process, small molecule biosynthetic process and cellular lipid catabolic process. In conclusion, hepatic transcriptome analysis shows that rumen-protected NA induces genes which are involved mainly in immune processes including acute phase response and stress response in dairy cows at wk 1 p.p. These findings indicate that supplementation of rumen-protected NA to dairy cows in the periparturient period may induce or amplify the systemic inflammation-like condition which is typically observed in the liver of high-yielding dairy cows in the p.p. period.

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Host–gut microbiota–bile acid axis integrates dietary starch to regulate milk fatty acid metabolism in dairy goats

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