Sung Woo Kim, Marcos Elias Duarte, Alexa R Gormley
The jejunum is the primary site for digestion, nutrient absorption, and protection from antigens and toxins, making its functional integrity during the post-weaning period a key determinant of growth performance in nursery pigs. Inflammatory and oxidative stress biomarkers in the jejunal mucosa are closely associated with growth performance and can serve as functional indicators of intestinal health under post-weaning conditions. Many biomarkers exhibit threshold responses, suggesting that variation below biologically meaningful breakpoints may have minimal impact on performance, whereas exceeding these thresholds results in performance reduction. Inflammatory and oxidative stress responses in the jejunum tend to impair growth prior to reductions in feed intake, cautioning that reliance on in-barn observations alone may underestimate early performance losses. Biomarkers should be interpreted within the appropriate biological context as understanding their relative sensitivity is imperative to early detection and subsequent intervention. The jejunum is the primary site of nutrient digestion and absorption. In the context of animal production, the efficiency of nutrient digestion and absorption heavily influences growth rates providing economic advantages to producers (Campbell et al., 2013; Patience et al., 2015). In addition, the jejunum is a part of the gastrointestinal tract, the largest immune organ in the body, that directly interacts with dietary and environmental antigens and toxins. The intestinal immune system is characterized by complex interactions between the native microbiota, intestinal epithelial cells, intestinal immune cells, and host signaling pathways that protect intestinal tissue and respond to potential threats (Burkey et al., 2009). Considering that the functional capacity of the jejunum related to both digestion and immune functions is a key determinant of production efficiency, maintaining intestinal integrity during the weaning transition is critical in modern pig production systems. However, when weaned at this early age, the intestine and its immune system are still immature (Moeser et al., 2017). As a result, nursery pigs are vulnerable to intestinal damage from weaning stress and pathogenic colonization causing inflammation and oxidative damages (Kim and Duarte, 2021). To support the function of the jejunum post-weaning, it is critical to understand interactions among the microbiota, jejunal epithelium, and its immune system, and how these relationships are influenced by external factors. Along the gastrointestinal tract the luminal and mucosa-associated microbiota differ in composition based on their location and substrate availability (Kelly et al., 2017; Adhikari et al., 2019). The mucosa-associated microbiota is physically associated with intestinal epithelial and immune cells; therefore, the small intestine is particularly sensitive to alterations in the composition of the mucosa-associated microbiota (Duarte and Kim, 2022). Common weaning-associated stressors, like abrupt dietary changes, toxins, and pathogen exposure, disrupt these microbial populations (Holanda and Kim, 2022; Garavito-Duarte et al., 2025). Pattern recognition receptors of the innate immune system continuously sample the mucosa-associated microbiota and recognize commonly conserved bacterial motifs, modulating immune signaling in response (Kawai and Akira, 2010). Interactions with beneficial bacteria promote tolerance and anti-inflammatory signaling, whereas interactions with pathogenic bacteria trigger pro-inflammatory signaling cascades that activate the immune system (Wells et al., 2011). Excessive activation of these pathways can induce inflammation and oxidative stress, compromising epithelial integrity and increasing energy demands for tissue repair (Gormley et al., 2024; Lopez-Rincon et al., 2026). This diverts energy away from growth and increases susceptibility to opportunistic or pathogenic bacterial populations, ultimately reducing growth. Understanding how weaning-induced intestinal damage affects the functions of the small intestine is essential to improve intestinal health and productivity of nursery pigs (Figure 1). Impacts of challenges associated with weaning on the jejunum of nursery pigs. Influences on the jejunal health and function have downstream effects on health and performance outcomes. To address these challenges, this review summarized the research findings using a series of meta-analyses to quantitatively evaluate how immune and oxidative stress biomarkers in the jejunal mucosa relate to growth performance in nursery pigs. Specifically, the first goal of this summary was to characterize the intestinal immune status of nursery pigs to differentiate between normal and challenged states. The second goal was to determine the impact of specific intestinal health biomarkers on growth and other relevant production parameters. The data from 38 studies involving 1,618 pigs were compiled to evaluate how intestinal health indicators relate to growth performance in nursery pigs. Across studies, pigs were managed under highly comparable conditions: pigs were individually housed, weaned at approximately 21 days-of-age and 6.5 kg body weight, and were sampled between 42 and 64 days of age. Diets were similar in composition and formulated to meet or exceed the requirements outlined in the Nutrient Requirements of Swine (NRC, 2012) and all studies followed consistent internal protocols for sample collection and laboratory analysis. All studies were conducted at North Carolina State University (Raleigh, NC, USA) and have been published in peer-reviewed journals (Table 1). List of studies used in the research summary.a All studies shared the following conditions: individually housed, mixed-sex pigs weaned at 21 days-of-age (approximately 6.5 kg body weight), and transported from a commercial to research facility with a transport duration of 2 hours. The experimental period ranged from 21 to 43 days. Growth performance was evaluated using average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) as dependent variables. These outcomes were examined in relation to key biomarkers including tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), immunoglobulin G (IgG), and immunoglobulin A (IgA), malondialdehyde (MDA) and protein carbonyl (PC), and villus height (VH), villus height-to-crypt depth ratio (VH:CD), and Ki-67 positive cells (Ki-67+), as independent variables. Each analysis included the subset of studies with relevant data (Tables 2–4). Data contributed from studies used for the meta-analysis (TNF-α, IL-8, and IL-6).a Abbreviations: TNF-α, tumor necrosis factor-α; IL-8, interleukin 8; IL-6, interleukin 6; ADG, average daily gain; ADFI, average daily feed intake; G:F, gain to feed ratio. Data contributed from studies used for the meta-analysis (IgG, IgA, MDA, and PC).a Abbreviations: IgG, immunoglobulin G; IgA, immunoglobulin A; MDA, malondialdehyde; PC, protein carbonyl; ADG, average daily gain; ADFI, average daily feed intake; G:F, gain to feed ratio. Data contributed from studies used for the meta-analysis (VH, VH:CD, and Ki-67+).a Abbreviations: VH, villus height; VH:CD, villus height to crypt depth ratio; Ki-67+, ratio of Ki-67+ to total cells in the jejunal crypt; ADG, average daily gain; ADFI, average daily feed intake; G:F, gain to feed ratio. The data were to the at independent affects the growth performance of nursery pigs using a as in by et The of the was included in the as a to for In or breakpoints were the was used to determine the appropriate the was the was and are in to the between intestinal health biomarkers and growth performance Abbreviations: TNF-α, tumor necrosis factor-α; IL-8, interleukin 8; IL-6, interleukin 6; IgG, immunoglobulin G; IgA, immunoglobulin A; MDA, malondialdehyde; PC, protein carbonyl; VH, villus height; VH:CD, villus height to crypt depth ratio; Ki-67+, ratio of Ki-67+ to total cells in the jejunal crypt; ADG, average daily gain; ADFI, average daily feed intake; G:F, gain to feed ratio. for and for or is the dependent ADFI, or associated with the in the the response of the dependent is the of the between and when the of the independent intestinal biomarkers independent of relevant production their These meaningful to the when can be related to outcomes that the productivity of pig production, like growth The production of ADG, ADFI, and are used as indicators of health et al., 2015). Many immune and within However, the at these in in performance relevant threshold data that be to both and A in the growth performance ADFI, was as a threshold as it a of that is sensitive to early to be and relevant in commercial pig A summary of the intestinal health biomarkers at and of growth performance is in health biomarkers at and of growth performance from the Abbreviations: TNF-α, tumor necrosis factor-α; IL-8, interleukin 8; IL-6, interleukin 6; IgG, immunoglobulin G; IgA, immunoglobulin A; MDA, malondialdehyde; PC, protein carbonyl; VH, villus height; VH:CD, villus height-to-crypt depth ratio; Ki-67+, ratio of Ki-67+ to total cells in the jejunal crypt; ADG, average daily gain; ADFI, average daily feed intake; G:F, gain to feed ratio. Growth performance the intestinal health the threshold and are as Growth performance at of necrosis factor-α is a pro-inflammatory by and As a key signaling the of immune cells to the site of or tissue In nursery the associated with weaning and the of and can induce in the intestinal that can damage the jejunal and impact growth performance (Holanda and Kim, 2022; et al., of in the jejunal mucosa are commonly used as a of intestinal inflammation (Kim and Duarte, 2021). However, production of is a normal of a functional innate immune system and can be based on the and duration of a for as as the to increases in key performance improve the of responses in weaned pigs. 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A meta-analysis of studies, involving to between intestinal health biomarkers and growth performance in nursery pigs. This was by the of in research the A primary of this summary is the of for jejunal mucosa including pro-inflammatory (TNF-α, IL-6, oxidative damage and intestinal integrity indicators (VH, VH:CD, for pigs to with of to These thresholds producers and to the health status of pig the analysis and as sensitive indicators of growth other suggesting that or reducing these specific and oxidative to intestinal integrity and growth Kim, is a and University at North Carolina State is as a of the for the of research on and and for intestinal health in pigs. Duarte, is a at in from the University of and at North Carolina State research on intestinal microbiota and for weaned pigs challenged with published on and functional to integrity and animal is a at North Carolina State University in the of in from State research on the of to improve intestinal health in weaned with on the of and This was for by the of The in this are of the and the or of the of the or the The from all and of at North Carolina State University (Raleigh, NC, of The or of Data and The from North Carolina NC, The USA) is to