Abstract Intrauterine growth restriction (IUGR) poses a significant challenge in swine production, affecting approximately 20% of piglets and resulting in increased mortality rates, metabolic disturbances, compromised intestinal development, and altered microbial colonization. This phenomenon arises as the IUGR fetus adapts to limited oxygen and nutrient supply in utero by reallocating blood flow towards vital organs, particularly the brain, consequently leading to a greater brain-to-liver weight ratio (BrW/LW) at birth. Our study aimed to comprehensively investigate the repercussions of IUGR on fecal microbiota composition and plasma metabolome profiles in pigs from birth through to slaughter. To elucidate these effects, we conducted computed tomography scans on piglets within 24 h of birth to assess brain and liver weights accurately. Subsequently, we selected two groups of piglets based on the BrW/LW. Specifically, 12 piglets with the greatest BrW/LW (IUGR; BrW/LW: 1.00 ± 0.09) and 12 with the least BrW/LW (NORM; BrW/LW: 0.36 ± 0.04). From these piglets we collected fecal and blood samples at specific time points: during lactation (T1: d 16 ± 0.6), after the starter period (T2: d 63 ± 8.6), and at the onset (T3: d 119 ± 11.4) and conclusion (T4: d 162 ± 14.3) of the finisher period. Throughout the study, all pigs received identical diets to eliminate dietary confounders. In the lactation, starter and grower but not finisher period, IUGR piglets grew 47, 19 and 14% slower, respectively compared with their NORM littermates. Our findings revealed that fecal microbial α-diversity remained unaffected by IUGR across all time points examined, indicating a stable microbial richness within the gut microbiota of IUGR and NORM pigs. However, β-diversity, reflecting inter-group microbial community variation, exhibited significant differences at T1 (P = 0.002), T2 (P = 0.079), and T3 (P = 0.027), suggesting distinct microbial compositions between IUGR and NORM pigs at these stages. Specifically, IUGR pigs displayed a greater abundance of Clostridium sensu stricto 1 and Romboutsia at T1, Prevotellaceae NK3B31 group, Rikenellaceae RC9 gut group, and Alloprevotella at T2, and p-2534-18B5 gut group at T3. Conversely, the NORM group exhibited increased concentrations of Ruminococcus at T1, HT002 at T2, and Prevotella_9 at T3. Furthermore, while plasma metabolite analysis revealed no significant differences between IUGR and NORM pigs at T1, decreased arginine levels were observed in the IUGR group compared with NORM at T2 (P < 0.05). In conclusion, our study underscores the profound and persistent impact of IUGR on fecal microbiota composition in pigs from birth to the initial stages of the finisher period, while suggesting minimal alterations in the blood metabolome profile throughout various growth stages. These findings provide valuable insights into the long-term consequences of IUGR on swine health and production. This research received funding from the European Union’s Horizon 2020 research and innovation program under a Marie Sklodowska-Curie grant (agreement no. 955374).
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