Background Enteric methane (CH4) emissions from ruminants are a major source of agricultural greenhouse gases and represent an energy loss to the host. Methyl-coenzyme M reductase (MCR) is the terminal enzyme in methanogenesis and represents a key target for CH4 mitigation. This study integrated computational screening, in vitro fermentation, and in vivo experiments to identify plant-derived compounds capable of reducing enteric CH4. Results Molecular docking of 3,900 phytochemicals identified proanthocyanidins (PAC) as top candidate, exhibiting strong predicted affinity to the MCR active site (-8.150 kcal/mol). In vitro rumen fermentation assays showed that PAC supplementation reduced CH4 production by 22% while increasing dry matter degradability. In lactating dairy cows, dietary PAC supplementation (10 or 20 g/kg dry matter) decreased daily CH4 emissions by ~ 8%, and improved ruminal nitrogen utilization without affecting milk yield or ruminal volatile fatty acid production. Amplicon sequencing and metagenomic analyses revealed PAC supplementation shifts in rumen microbial community, characterized by increased relative abundance of Bacteroidota taxa and a decreased relative abundance of methanogenesis-related genes. Functional genes associated with carbohydrate, lipid, and nitrogen turnover were more abundant, indicating potential improvements in nutrient utilization. Consistent with these changes, untargeted metabolomics likewise identified shifts in metabolite profiles that may associated with alternative routes for utilizing reducing equivalents. Conclusions This study provides integrated computational, microbial, and physiological evidence that PAC supplementation can reduce enteric CH4 emissions in lactating dairy cows, inducing rumen microbial and functional shifts and improving nitrogen utilization. These findings support the potential of PAC as a natural approach to lowering CH4 emissions and advancing sustainable dairy production. <MediaObject ID="MOESM3"> <VideoObject FileRef="MediaObjects/40168_2026_2406_MOESM3_ESM.mp4" VideoID="8g9TPeVDaX-LsNNt5oM68S"> <Caption Language="En" xml:lang="en"> <CaptionContent> Video Abstract </CaptionContent> </Caption> </VideoObject> </MediaObject> Graphical Abstract

Proanthocyanidins inhibit methane emissions by interacting with methyl-coenzyme M reductase and reshaping rumen microbiome function

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2026年5月7日

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Zihao Liu,
Yuming Guo,
Li Xiao,
Jian Guo,
Yuxuan Chen,
Hui Wang,
Xuemei Nan,
Mengting Zhou,
Fan Zhang,
Yue He,
Zhixue Yu,
Rong Wang,
Zhuqing Ren,
Jian Wu,
Min Wang,
Xiangfang Tang,
Benhai Xiong

摘要

Background

Enteric methane (CH₄) emissions from ruminants are a major source of agricultural greenhouse gases and represent an energy loss to the host. Methyl-coenzyme M reductase (MCR) is the terminal enzyme in methanogenesis and represents a key target for CH₄ mitigation. This study integrated computational screening, in vitro fermentation, and in vivo experiments to identify plant-derived compounds capable of reducing enteric CH₄.

Results

Molecular docking of 3,900 phytochemicals identified proanthocyanidins (PAC) as top candidate, exhibiting strong predicted affinity to the MCR active site (-8.150 kcal/mol). In vitro rumen fermentation assays showed that PAC supplementation reduced CH₄ production by 22% while increasing dry matter degradability. In lactating dairy cows, dietary PAC supplementation (10 or 20 g/kg dry matter) decreased daily CH₄ emissions by ~ 8%, and improved ruminal nitrogen utilization without affecting milk yield or ruminal volatile fatty acid production. Amplicon sequencing and metagenomic analyses revealed PAC supplementation shifts in rumen microbial community, characterized by increased relative abundance of Bacteroidota taxa and a decreased relative abundance of methanogenesis-related genes. Functional genes associated with carbohydrate, lipid, and nitrogen turnover were more abundant, indicating potential improvements in nutrient utilization. Consistent with these changes, untargeted metabolomics likewise identified shifts in metabolite profiles that may associated with alternative routes for utilizing reducing equivalents.

Conclusions

This study provides integrated computational, microbial, and physiological evidence that PAC supplementation can reduce enteric CH₄ emissions in lactating dairy cows, inducing rumen microbial and functional shifts and improving nitrogen utilization. These findings support the potential of PAC as a natural approach to lowering CH₄ emissions and advancing sustainable dairy production.

Video Abstract

Graphical Abstract