Rising antibiotic resistance and growing demand for sustainable livestock practices have driven increasing interest in marine algae as a renewable source of bioactive compounds with reported immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial activities that may enhance disease resistance in pigs (Susscrofa) [1]. Marine algae produce a large variety of structurally distinct biologically active molecules, such as sulfated polysaccharides, polyphenols, carotenoids, bioactive peptides, and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) [1]. Their biological activity is closely linked to their structure, how they interact with host immune receptors, and how they affect downstream signalling. Significant pathways involved are the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2), which control cytokine production and oxidative stress reactions [1].

One of the most therapeutically relevant metabolites of these marine algae is sulfated polysaccharides, which include fucoidans and carrageenans. Their effects are seen in enhancing innate immunity, inhibiting viral replication, and reducing inflammation in a variety of mammalian model systems [1][2]. The properties make them attractive to be used as feed additives or immunonutritional supplements in commercial pig production.

The porcine system of Susscrofa is highly complex, involving complex networks of cytokines, innate immune sensors, and adaptive lymphocytes [3]. It is crucial to balance pro-inflammatory and regulatory signals. Such as, interleukin-12 (IL-12) and Interferon-gamma (IFN-γ) as an example of pro-inflammatory signalling, and interleukin-4 (IL-4) and interleukin-10 (IL-10) are examples of regulatory signalling, to ensure optimal vaccine efficacy, disease protection, and avoid immunopathological sequelae [4].

The utilization of marine algae-based bioactives in PLF could be a novel approach to provide specific immunotherapeutic support to pigs, optimize animal well-being, and decrease the reliance on antibiotics. Current PLF systems include real-time monitoring, a network of sensors and integration of genetic information to enable individual animal health management and accurate medical interventions [5][6]. PLF could potentially allow algal bioactive feeds to be customised on a per-animal basis based on animal health condition, microbiota composition and environmental parameters, which would result in a more specific dietary immune-nutrition strategy based on Susscrofa immunometabolism than blanket antibiotic feeding.

This review 1) provides an overview of the most important classes of bioactives that have been identified in marine algae, including microalgae and macroalgae and have potential relevance for swine, 2) examines the proposed immunological mechanisms and the level of supporting evidence, and 3) explores the potential of PLF to achieve targeted, stage-specific delivery.

A comprehensive literature review was performed using electronic databases including PubMed, Semantic scholar and Google Scholar. We used various keyword combinations such as “marine algae”, “Susscrofa”, “bioactive metabolites”, “immunomodulation”, “immunotherapy” and “precision livestock farming” to find studies that were published in English between 2000 and 2025. Boolean operators (AND/OR) were used to adjust the search strategy. Only original experimental studies, systematic reviews, and mechanistic or cross-species studies on the effects of compounds derived from marine algae on mammalian immunity, specifically in Susscrofa, were included. Conference abstracts and grey literature were not included in the primary evidence base. When commercial product data are referenced, the reference and the evidence sources are identified and non-peer-reviewed or industry-sponsored data are separated from independently replicated data.

Marine algae produce diverse bioactive compounds which have potential uses in medicine and nutrition. Among the most frequently studied classes are polysaccharides and polyphenols [1][7]. Sulfated polysaccharides show significant immunomodulatory and antiviral effects, with their biological activity determined by the sulfate groups and molecular weight differences [7]. In particular, fucoidans and carrageenans have been shown to regulate the expression of genes that are essential to innate immune responses, and to possess therapeutic potential in neuroinflammatory diseases; the mechanisms of their action seem to involve regulation of key transcription factors and downstream regulation of cytokine production [8].

Another important class of compounds is phlorotannins, a group of polyphenols only found in brown algae. Species like Fucus vesiculosus,Ascophyllumnodosum and Ecklonia cava contain very high levels of phlorotannins with strong antioxidant properties, which include reactive oxygen species (ROS) scavenging and chelating of redox-active metal ions, as well as anti-inflammatory effects, by inhibiting the production of pro-inflammatory cytokines, especially tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) [8]-[10]. Phlorotannins, particularly, because of their dual anti-oxidant and anti-inflammatory properties, are important for the management of immune pathologies caused by oxidative stress [11].

Carotenoids are another group of bioactives of interest. In microalgae, carotenoids, including astaxanthin, fucoxanthin and β-carotene, are synthesized along with other protective molecules like fatty acids and sulfated polysaccharides in response to abiotic stress in species like Chlorella zofingiensis, Haematococcus pluvialis, and Spirulina platensis [12]. They act as antioxidants in the organism that produces them and have significant immunomodulatory activity in mammalian cells [12].

Bioactive peptides (usually small peptides between 3 and 20 amino acids) extracted from algae like Chlorella vulgaris and Spirulina spp. have been shown to have immunoregulatory, antimicrobial, and anti-inflammatory effects by modulating cytokines and directly binding to microbial and host cell membranes [13][14]. Lastly, ω-3 PUFAs from microalgae, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and α-linolenic acid (ALA), are known to exert anti-inflammatory, cardioprotective and neuro-modulatory properties by modulating eicosanoid biosynthesis and membrane fluidity [15][16]. Table 1 is a tabulated description of these large groups of compounds, their sources in algae and principal modes of action.

Important is the gastrointestinal fate, as most of these compounds are used as complex algal preparations as opposed to pure compounds. These sulfated polysaccharides like fucoidan, carrageenan, laminarin, and ulvan are polysaccharides of high molecular weight, which are not expected to be completely digested by host enzymes, and therefore, some of their activity may take place locally in the gastrointestinal tract; however, microbial transformation can generate lower molecular weight fragments or metabolites that have different biological properties [17]. Phlorotannins are also poorly absorbed in the small intestine, with large molecules being metabolized by colonic bacteria into smaller molecules that can then be absorbed [18]. Carotenoids like fucoxanthin must be incorporated into lipid-containing micelles in the intestine to be absorbed and taken up into the blood and can be metabolized to fucoxanthinol and amarouciaxanthin A prior to systemic distribution [19]. Bioactive peptides are susceptible to gastric and intestinal proteolysis, which means that the amount of exposure by intact peptides is probably lower than the ingested amount of peptides, but smaller peptides or amino acids may be absorbed [20]. EPA and DHA, however, and the other fatty acids derived from algae, are broken down and taken up like normal lipids, and can then be used to build circulating lipids and cell membranes. Therefore, using cell-based mechanisms to infer systemic effects in pigs cannot be assumed without knowledge of the bioactive compound exposure, whether it be luminal or microbiota-mediated, and porcine studies of digestion, metabolism and tissue exposure are important gaps.

Table 1. Marine algae bioactive compounds, examples, mechanism of actions and their properties.

The extraction techniques determine the resulting yields and purity of these bioactive compounds. The conventional method of solvent extraction is now being replaced by modern technologies such as enzyme-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, supercritical fluid extraction and pressurized liquid extraction [7][21]. These modern extraction methods achieve better results because they require shorter processing times, improved yields and maintain the stability of heat-sensitive materials [21].

In marine algae, the chemical composition is quite varied from species to species. The total polysaccharide content and uronic acids of three typical species (Chlorophyta Ulva lactuca, Phaeophyta Sargassum crassifolia, and Rhodophyta Digenea simplex) have been reported as 57 - 185 mg/g dry weight and 29 - 45 mg/g, respectively. Sulfate moieties and amino acids have been reported as 95 - 181 mg/g and 7 - 17 mg/g, respectively [22]. Sulfated polysaccharides are important structural and functional components of algal cell walls that have been characterised by Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectroscopy, which have revealed antioxidant properties [23][24].

Below are conceptual figures of therapeutic activity spectra of marine algal bioactives useful for Susscrofa as an emerging immunotherapy. These figures are used as qualitative interpretative summaries and all proportions and relationships shown are based upon qualitative interpretation of the literature and are not statistically or quantitatively based on primary data. Figure 1 shows the different broadness of bioactivity of the major classes of compounds found in marine algae from targeted domain-specific effects, e.g., omega-3 PUFAs [15][16] and glyceroglycolipids [25] to broad, multi-domain activity, e.g., sulfated polysaccharides [1][7][8][21], phlorotannins [8]-[11][26], carotenoids [12][23] and bioactive peptides [13][14][27].

Figure 1. Illustrative conceptual summary; not a data-derived or evidence-weighted representation [1][7]-[16][26]-[30].

Figure 2. Illustrative conceptual representation; contribution levels are qualitative and not quantitatively derived from the literature [1][7]-[16][26]-[35].

A compound class-by-therapeutic domain activity matrix is shown in Figure 2, which was derived from the compound-specific evidence listed above [1][7]-[16][26]-[35]. The activity map demonstrates how each compound class contributes to therapeutic domains. It shows different types of contributions, which include primary, secondary and limited/indirect contributions. The marine algae compounds demonstrate their ability to provide complementary biological activity through their various bioactive properties.

Figure 3. Illustrative conceptual summary; profiles reflect qualitative interpretation of the literature and are not statistically derived [7]-[14][26][27][29][30][34][35].

The mechanisms underlying each therapeutic domain are shown in specific molecular and physiological processes in the Figure 3 above: the antioxidant activity through reactive oxygen species (ROS) scavenging and activation of the Nrf2 pathway by phlorotannins and carotenoids [8]-[12][26][30]; the antimicrobial activity through minimum inhibitory concentration (MIC) of bioactive peptides [13][14]; the antiviral activity through inhibition of viral replication by sulfated polysaccharides [7][8][34][35]; the anticancer/cytotoxic activity through induction of apoptosis by sulfated polysaccharides, carotenoids and bioactive peptides [26][27][29]; the hepatoprotective activity through sulfated polysaccharides and carotenoids [26][29]; the neuroprotective activity in the central nervous system (CNS) through phlorotannins [30]; the anti-inflammatory activity through suppression of tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by phlorotannins and ω-3 PUFAs [8]-[10][15][16].

Bioactive metabolites of marine algae are emerging as promising feed-level immunotherapeutics for Susscrofa that can enhance natural and acquired immune responses, reduce unnecessary inflammatory responses, and improve vaccine efficiencies in commercial production systems [36]. The most researched compounds relevant to swine applications are sulfated polysaccharides, β-glucans, and algal peptide-rich extracts, which can be added to the diet without significant changes in farming practices [34][36].

The integration of PLF with Susscrofa production has the potential to revolutionize marine-algal bioactive metabolites from a static feed additive to a dynamic immunotherapeutic agent delivered in response to real-time health status, not universally across a population [40]. Modern PLF systems use sensors, cameras and AI algorithms to monitor individual pig movement, feed intake behaviour and vocalisation patterns to detect early immune activation, stress or subclinical disease [40][41]. In principle, these detection capabilities could allow the targeted delivery of algal-derived immunomodulators like sulfated polysaccharides, β-glucans and ω-3-rich microalgal preparations through automated feeding and dosing systems calibrated to the health status and production stage of specific pigs or groups of pigs (neonates, weaners and gestating sows) [42].

PLF platforms have already proved to be more precise than human observers in the detection of sick or stressed pigs [41], and commercial swine operations are beginning to implement functional feed ingredients in smart-feeding systems where feeding algorithms adapt the dietary inclusion level of algae-rich meals or algal functional ingredients (e.g., ω-3 DHA from microalgae, algal β-glucans) depending on individual health trajectories and production phases [42]. Yet, it is important to bear in mind that closed-loop PLF systems that can provide truly immune-targeted feed are still conceptual; their implementation will require validated immunological biomarkers, interoperable dosing infrastructure that links sensor data to feed-mill outputs, and proven economic feasibility under commercial conditions.

The early life to post-weaning stage is a particularly high-priority window for immune-nutritional intervention in Susscrofa. This developmental stage is characterized by rapid maturation of the immune system but increased susceptibility to enteric disease and respiratory infections [42]. The evidence reviewed suggests that supplementation with seaweed and microalgae may be beneficial for improving gut function and immunoglobulin transfer during colostrum intake and may potentiate PRRSV vaccine-induced humoral immunity [34]. A PLF system capable of recognising early behavioural markers of immune challenge in weaner groups, such as decreased feed intake, increased lying times and alterations in vocalisation patterns, may initiate algal-based immune support at the most opportune moment for it to be successful. Completing this validation loop between PLF-detected signals and outcomes of algal supplementation is a key translational priority for future research.

A major challenge to the development of marine algal bioactives as licensed immunotherapeutic agents for Susscrofa is the lack of standardized production and quality assurance frameworks for raw algal biomass and purified fractions (sulfated polysaccharides, β-glucans and algal peptides). Variability in the chemical composition between batches due to differences between species, growth conditions and the method of harvesting and extraction can lead to inconsistent effects on the immune system. If the quality of the composition is not well-controlled, there is a risk of unwanted reactions that cause inflammation or hypersensitivity. Moreover, the possible accumulation of heavy metals, biotoxins and anti-nutritional factors in the biomass of algae presents real safety concerns that require the implementation of strong quality-control systems and safety standards of regulatory quality before such products are routinely incorporated into commercial swine diets. Future research programmes should focus on the development of harmonised testing and extraction protocols, standardised immune and gut-health outcome endpoints and coordinated partnerships between academic institutions, industry and regulatory authorities towards evidence-based guidelines for the use of bioactive marine algal metabolites in Susscrofa production systems.

This is further complicated by the dose and context dependency of the immunomodulatory effects of algal metabolites in Susscrofa. Low to moderate levels of dietary inclusion appear to promote immune function and gut health, with high doses potentially eliciting undesirable physiological responses or metabolic disruption. Dosing requirements are likely to vary markedly between life stages (sow, piglet, weaner and growing-finishing pigs) and production systems (conventional, organic and antibiotic-reduced), but the current literature provides little quantitative guidance on dose-response relationships in swine. Future mechanistic studies will be required to determine safe and effective dosing ranges for the primary algal immunomodulatory fractions and to characterise potential interactions with co-administered vaccines, antibiotics and other feed additives.

Moreover, the delivery of targeted algal-based immunotherapy to Susscrofa through the PLF system needs to solve both technical and economic problems that prevent its successful application. The current PLF systems succeed in capturing comprehensive behavioural and physiological information, but they lack immunotherapeutic connections to immune-targeted feed delivery systems and algal response algorithms, while their components from different sensor manufacturers and feed mills and farm management software systems remain unconnected. Future research development for Susscrofa should focus on closed-loop systems which use “algae-PLF” modules to determine the optimal algal-immunomodulator levels through validated health indicators and cost-benefit assessments which show better treatment outcomes and improved animal welfare and production results without using antibiotics.

The studies reviewed offer compelling evidence for the substantial potential of marine algae bioactive metabolites as an emerging novel agent for the immunotherapeutic treatment of Susscrofa. The evidence presented in the porcine in vitro mechanistic studies, controlled in vivo trials, and cross-species data can be ranked according to confidence, each of which lies on top of the previous one:

Well supported evidence:

The NF-κB/MAPK signalling activation is inhibited through sulfated polysaccharides, which show their effects in multiple studies that use porcine macrophage and dendritic cell models as test systems. The intestinal TNF-α is decreased by fucoidan-rich dietary preparations at an inclusion level of about 0.2% in vivo, which can be used as a reference level for dose-ranging.In controlled in vivo studies in pigs, algal β-glucan supplementation has been shown to enhance the integrity of the gut barrier and to attenuate inflammation provoked by E. coli. The results are most directly relevant to commercial weaner diets and should be replicated at multiple sites.

Promising but requires stronger evidence:

Technically, the idea of PLF-based adaptive algal dosing is well-founded, with current sensor-AI options available in commercial swine farms. However, closed-loop PLF systems for delivery to specific immune targets have not yet been demonstrated, and the critical validation loop between PLF-detected behavioural signals and immunological response outcomes is not complete.Most of the immunostimulatory evidence for carotenoids and polyphenols is from models other than porcine or in vitro. The bioavailability, metabolism and dose-response information for the species Susscrofa is not complete enough to make strong recommendations for doses.

Research gaps to address:

Research needs to conduct multi-site randomized controlled trials to determine the minimum effective dose and maximum safe dose of fucoidan, β-glucan and ω-3 fractions, which need to be tested on neonates, weaners, gestating sows and growing-finishing pigs through standardized immune endpoints which include serum cytokine profiles and vaccine-specific antibody titres and gut permeability markers. Regulatory-grade testing needs to assess heavy metals, which include arsenic, cadmium and lead, as well as biotoxins and anti-nutritional factors across all commercially relevant algal species and their harvest batches before any large-scale feed application. The existing lack of safety information now stands as the main obstacle that prevents regulatory bodies from granting their approval.The inter-laboratory standardization of sulfate content, molecular weight distribution, and polyphenol concentration tests needs standardization because it enables researchers to compare their results through various research studies. The absence of established reference materials makes it impossible to conduct accurate dose assessments between different studies.

The PLF testing for immune endpoints needs prospective research to determine whether PLF-detected behavioural signals (reduced feed intake, prolonged recumbency, altered vocalizations) can predict immune activation events in Susscrofa and whether algal inclusion adjustments will result in measurable long-term immunological advantages. The validation loop needs completion because it represents the essential transition from scientific concept to practical clinical application.

Godwin Femi Ekundayo: conceptualization, methodology, investigation, data curation, formal analysis, visualization, writing—original draft, writing—review & editing. Daniel Oluwaleke Biaoku: conceptualization, methodology, supervision, validation, resources, writing—review & editing.