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Background: Coccidia are among the primary pathogens causing diarrhea and even fatalities in lambs. With the increasing use of chemical drugs to treat coccidiosis, the problem of drug resistance is becoming more and more threatening. Therefore, there is an urgent need to identify novel alternative drugs for the treatment of the lamb coccidia. In this study, the effect of different doses and extraction methods of Artemisia annua (A. annua) on anticoccidial activity and growth performance was assessed by oocysts output (OPG), fecal index, average daily gain (ADG) and the new production value of experimental lambs. High-throughput sequencing technology was employed to investigate the effect of A. annua on the intestinal microbiota and metabolites of lambs afflicted with coccidiosis., Results: The results revealed that all A. annua treatment groups exhibited good anticoccidial effects. According to the soft stool index and ADG analysis, the Low-dose A. annua (AL) and A. annua alcohol extract (AA) groups demonstrated a better overall effect. The microbiota and metabolites of lambs changed after A. annua was administered. Unclassified&#95;Muribaculaceae exhibited a significant positive correlation with ADG (P < 0.05) and a negative correlation with OPG, although the latter was not statistically significant (P > 0.05). Alistipes displayed a significant negative correlation with ADG (P < 0.05), and a positive correlation with OPG (P > 0.05). Additionally, UCG 005 exhibited a highly significant negative correlation with OPG (P < 0.01)., Conclusion: The above results demonstrated that AL and AA groups had more effective anticoccidial action. Unclassified&#95;Muribaculaceae could be employed as a suitable probiotic to enhance weight gain in lambs, while UCG-005 could inhibit intestinal Eimeria colonization in lambs. Alistipes may serve as a biomarker for predicting the risk of intestinal coccidia outbreaks in lambs. A. annua induced significant changes in gut microbiota, accompanied by corresponding changes in metabolites. These differences in gut microbiota and metabolites provide valuable insights for subsequent research on the mechanisms underlying anticoccidial action., Competing Interests: Declarations. Ethics approval and consent to participate: The Research Ethics Committee of Henan Agricultural University reviewed and approved the experimental protocol. The collection of samples was performed following the Guide for the Care and Use of Laboratory Animals (Ministry of Health, China). All samples tested in this experiment were collected with permission from herders, while no special permission was required for sampling locations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Sheep coccidiosis could disturb the balance of intestinal microbiota, causing diarrhea, and even death in lambs. Chemical drugs are the primary method of treating sheep coccidiosis, but their use will bring drug resistance, toxic side effects, drug residues, and other problems. Chinese herbal medicines are investigated as alternative methods for controlling coccidian infections., Methods: In this study, the effect of fermented Artemisia annua (FA) on oocysts per gram (OPG), average daily gain (ADG), and expression of inflammatory factors were investigated in lambs that were naturally infected with coccidia., Results: The results showed that the FA had similar anti-coccidiosis effect to the original drug, while the FA demonstrated a more significant effect on weight gain, and a better ability to reduce the inflammatory response compared to the unfermented drug during the treatment period ( P < 0.05). Furthermore, High-throughput sequencing technology was used to study the effects of FA on intestinal microbiota, and fecal metabolites of naturally infected lambs. The species richness of intestinal microbiota of lambs was significantly improved by FA. The abundance of bacteria unclassified&#95;Muribaculaceae , and UCG&#95;005 were increased by fermentation of A. annua . The abundance of bacteria Escherichia&#95;Shigella , unclassified&#95;Clostridia&#95;UCG&#95;014 , and Alistipes was reduced. The prevention, and treatment of coccidiosis by fermentation of A. annua may also be related to a series of metabolites affected by intestinal microbiota, including artemisinin, Lysyl-Proline, and TRP-tyrosine., Conclusion: FA was found to have superior anti-coccidiosis, anti-inflammatory, and weight gain effects compared to the original Artemisia annua . Intestinal microbes and metabolites such as unclassified&#95;Muribaculaceae , UCG-005 , and Artemisinin were identified, suggesting their potential significance. Alistipes was proposed as a biomarker for predicting intestinal coccidia outbreak risk in lambs, pending further validation. The correlation between microbiota, and metabolites may provide new insights into pathogenic changes associated with Eimeria spp., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Liu, Li, Lu, Yang, Liu, Li, Li and Jian.)