From AGPs To Anti-Inflammatories: Rethinking Gut Health

Ecolex Animal Nutrition is committed to a holistic One Health approach, advancing antimicrobial resistance (AMR) mitigation by translating new insights into the mode of action of antibiotic growth promoters (AGPs) into sustainable nutritional solutions that maintain animal performance without AMR risks. This article summarizes emerging science on how AGPs function and how nutrition-based, anti-inflammatory strategies can mimic their benefits without relying on antibiotics.

AGP Modes of Action: More Than Antimicrobial Effects

Despite their extensive use since the 1950s, the mechanisms of action of AGPs remain incompletely understood. Historically, four main mechanisms for AGP effects on animal growth have been attributed primarily to their antimicrobial effects:

·        Reduced nutrient competition from gut microorganisms

·        Reduction of growth-depressing bacterial metabolites

·        Enhanced nutrition absorption due to reduced intestinal wall thickness

·        Inhibition of subclinical infections that divert energy from growth

The search for alternatives to AGPs has intensified due to widespread antimicrobial resistance (AMR), growing societal concerns, and increasing regulatory demands. To identify effective alternatives, it is essential to better understand how AGPs work and then search for non-antibiotic compounds with similar functional properties.

AGPs Target Low-Grade Inflammation

Modern animal production systems  often predispose animals to chronic low-grade intestinal inflammation, driven by metabolic stress, dietary challenges (antinutritional compounds, mycotoxins, excess dietary protein and oxidized lipids and microbiota imbalances, which directs energy away from growth toward immune function.

Several studies suggest that, beyond direct antimicrobial activity, other mechanisms must contribute to the growth-promoting effects of AGPs. AGPs appear to dampen chronic low-grade gut inflammation without completely suppressing immune function.

In a 2024 Poultry Science article, Miyakawa et. al. propose that sub-therapeutic AGPs act as low-dose stressors on host cells, triggering adaptive protective pathways that improve efficiency and reduce the energetic cost of inflammation. They argue that the traditional focus on direct antimicrobial effects does not fully explain why diverse classes of antibiotics produce similar growth responses, and instead propose mitochondrial hormesis as the primary driver.

Key mechanisms proposed include:

• Mitochondrial hormesis - Low-dose antibiotic exposure induces mild mitochondrial stress, triggering adaptive responses (hormesis) that enhance mitochondrial function rather than causing cell death.

• Disease tolerance over resistance - Instead of  mainly killing bacteria (resistance), AGPs increase resilience by reducing tissue damage and improving metabolic efficiency (disease tolerance).

• Mitokine signaling - Local mitochondrial disruptions in the gut mucosa promote the release of signaling molecules (mitokines) that modulate immune responses and metabolism throughout the organism.

• Reduced inflammation energy cost - By limiting chronic low-grade inflammation, AGPs reduce immune-related energy expenditure and free more nutrients for growth.

Supporting Evidence from Recent Studies

Nursery Pigs: In-feed sub-therapeutic chlorotetracycline (CTC) supplementation increased nursery pig growth performance, primarily by stimulating feed intake. Helm et. al. (2019) reported that ileal integrity, function, and cecal microbial metabolism did not fully explain this response. However, ileal transcript changes suggested a reduction in intestinal inflammation in CTC-fed pigs.

Broiler Chickens: In two broiler trials, Oh et. al. (2019) challenged 1-week old birds with Eimeria maxima and Clostridium perfringens and compared a basal diet supplemented with subtherapeutic levels of virginiamycin or bacitracin methylene disalicylate. Their results support the hypothesis that dietary AGPs can improve growth, in part, by down-regulating pathogen-induced inflammatory responses.

Broilers and Antioxidant Properties: In broilers challenged with lipopolysaccharide, Kabploy et. al.(2016) concluded  that the anti-oxidative and immunomodulatory properties of AGPs (avilamycin and flavophospholipol)  represent an indirect mechanism promoting animal health and production.

The Anti-Inflammatory Hypothesis: Most lines of evidence point toward an anti-inflammatory role for AGPs that reduces energy wastage  and spares nutrients for production, as highlighted by Niewold (2007). Intestinal inflammation typically leads to the accumulation of inflammatory cells in the mucosa, and a thicker intestinal wall, which increases maintenance costs and impairs nutrient absorption. Effective alternatives to AGPs should therefore be sought among non-antibiotic compounds with similar properties that can accumulate in inflammatory cells and attenuate the inflammatory response.

Mimicking AGPs Without AMR Risks

These findings have significant implications for the development of effective alternatives to AGPs in sustainable animal production. By prioritizing nutritional strategies and feed additives that reduce gut inflammation, rather than antimicrobial activity, we can maintain animal health and productivity while lowering reliance on antibiotics, and contributing to the global fight against AMR. This shifts the focus from “killing pathogens” to “supporting host resilience and intestinal integrity” through targeted nutritional interventions.

Ecolex’s Approach

Numerous studies indicate that glycerol monolaurate (GML) can decrease inflammation and modulate the immune response. GML has been shown to exhibited anti-inflammatory properties by downregulating pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, while upregulating anti-inflammatory mediators like IL-10 and TGF-β1 in broiler chickens and other species. (Chen 2024).

Ecolex’s advanced emulsification technologies, including products like Lipo ZAP (emulsified α-GML), are designed to deliver GML efficiently to the intestinal mucosa, helping to modulate inflammation and support barrier function. This allows farmers to support gut health and productivity while minimizing the need for antibiotics, protecting animal welfare and contributing to long-term public health sustainability.

By targeting low-grade intestinal inflammation and supporting mitochondrial and immune resilience, such solutions aim to mimic key benefits historically attributed to AGPs—without AMR risks.

Ecolex also recognizes that moving away from AGPs toward nutrition-based gut health solutions requires a holistic One Health strategy. This includes attention to strict biosecurity and hygiene, sound management practices, and effective vaccination programs to sustain animal health and resilience across the production system.

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Fernández Miyakawa, Mariano E., et al. “How Did Antibiotic Growth Promoters Increase Growth and Feed Efficiency in Poultry?” Poultry Science, Vol. 103, Issue. 2, February 2024, Article 103278 https://www.sciencedirect.com/science/article/pii/S0032579123007976

Other references available on request.