Postpartum Systemic Inflammation is Reflected in Early Distinct Fecal Microbiome Differences in Dairy Cows

A tightly regulated inflammatory response occurs during and following parturition; however, excessive or prolonged inflammation negatively affects herd health and productivity. The gut microbiota plays an important role in host immunity and metabolism and undergoes substantial changes during the transition period. However, the relationship between systemic inflammation, measured by serum acute-phase proteins, and gut microbial dynamics during early lactation remains poorly understood. We investigated fecal microbiota dynamics in relation to systemic inflammation in early postpartum dairy cows. Fecal and blood samples were collected from 71 Holstein cows on days 1 and 3 in milk (DIM). The V3-V4 region of the 16S rRNA gene was sequenced and microbial diversity, differential abundance, and microbial interaction networks were evaluated. Inflammatory status, defined by fibrinogen, haptoglobin, and their combined classification, was associated with significant alterations in fecal microbial composition during the immediate postpartum period, independent of body condition score, parity, DIM, and DNA extraction parameters. Differential abundance analyses revealed extensive taxonomic restructuring, while network analyses identified increased modularity, altered keystone taxa distribution, and greater compartmentalization of microbial interactions in animals with elevated inflammatory markers. Several taxa were consistently associated with inflammatory status across analytical approaches. Notably, Ruminococcaceae UCG-002 and Dielma were associated with inflammatory states, whereas Xylanibacter, Marvinbryantia, Akkermansia, and Oscillibacter were associated with non-inflammatory status. This study identifies an association between systemic inflammation and fecal microbiota composition in early transition dairy cows, providing a foundation for future microbiome-based biomarkers of inflammatory status. IMPORTANCESubclinical systemic inflammation during early postpartum can negatively affect dairy cow health and productivity, yet current monitoring relies on repeated blood sampling and transient inflammatory biomarkers. For the first time association of systemic inflammation, assessed using fibrinogen, haptoglobin, and their combined classification, with alterations in fecal microbial composition, microbial interaction networks, and keystone taxa distribution during the early postpartum period was established. Several bacterial taxa were consistently associated with either elevated or normal inflammatory states across differential abundance, network, and odds ratio analyses. Many of these taxa remain poorly characterized in dairy cattle, highlighting the need for future mechanistic studies. This study demonstrates that systemic inflammation during early postpartum is associated with measurable alterations in the fecal microbiota. This work provides a foundation for developing microbiome-based biomarkers for detecting and monitoring subclinical systemic inflammation in dairy cattle.