Macrophages are multifunctional immune cells whose functions depend on polarizable phenotypes and the microenvironment. Macrophages have two phenotypes, including the M1 proinflammatory phenotype and the M2 anti‐inflammatory phenotype, which play important roles in many inflammatory responses and diseases. α‐Ketoglutarate is a key metabolite of the TCA cycle and can regulate the phenotype of macrophage polarization to exert anti‐inflammatory effects in many inflammation‐related diseases. In this review, we primarily elucidate the metabolism, regulatory mechanism, and perspectives of α‐ketoglutarate on macrophages. The regulation of macrophage polarization by α‐ketoglutarate may provide a promising target for the prevention and therapy of inflammatory diseases and is beneficial to animal health.

Methionine (Met) metabolism provides methyl groups for many important physiological processes and is implicated in multiple inflammatory diseases associated with the disrupted intestinal microbiota; nevertheless, whether intestinal microbiota determines Met metabolism in the host remains largely unknown. Here, we found that gut microbiota is responsible for host Met metabolism by using various animal models, including germ-free (GF) pigs and mice. Specifically, the Met levels are elevated in both GF pigs and GF mice that mainly metabolized to S-adenosine methionine (SAM) in the liver. Furthermore, antibiotic clearance experiments demonstrate that the loss of certain ampicillin- or neomycin-sensitive gut microbiota causes decreased Met in murine colon. Overall, our study suggests that gut microbiota mediates Met metabolism in the host and is a prospective target for the treatment of Met metabolism-related diseases.

The global escalation of organic waste generation, coupled with rising protein demand and environmental pressure, necessitates innovative, circular approaches to resource management. Hermetia illucens (Black Soldier Fly, BSF) has emerged as a leading candidate for integrated waste-to-resource systems. This review examines BSF biological and genomic adaptations underpinning waste conversion efficiency, comparative performance of BSF bioconversion versus traditional treatments, nutritional and functional attributes, techno-economic, regulatory, and safety barriers to industrial scale-up. Peer-reviewed studies were screened for methodological rigor, and data on life cycle traits, conversion metrics, and product compositions were synthesized. BSF larvae achieve high waste reductions, feed-conversion efficiencies and redirect substrate carbon into biomass, yielding net CO₂ emissions as low as 12–17 kg CO₂ eq ton⁻¹, an order of magnitude below composting or vermicomposting. Larval biomass offers protein, lipids (notably lauric acid), micronutrients, chitin, and antimicrobial peptides, with frass serving as a nutrient-rich fertilizer. Pathogen and antibiotic resistance gene loads decrease during bioconversion. Key constraints include substrate heterogeneity, heavy metal accumulation, fragmented regulatory landscapes, and high energy and capital demands. BSF systems demonstrate superior environmental and nutritional performance compared to conventional waste treatments. Harmonized safety standards, feedstock pretreatment, automation, and green extraction methods are critical to overcoming scale-up barriers. Interdisciplinary innovation and policy alignment will enable BSF platforms to realize their full potential within circular bio-economies.

Safe antibiotic substitutes are needed given the rise in antimicrobial resistance, environmental contamination, and stringent antibiotic regulations. Insect-derived antimicrobial peptides (AMPs) are promising candidates due to their antimicrobial activity, stability, and safety. This study investigates the antimicrobial mechanism of crude AMP extracts and their physicochemical characteristics in black soldier fly larvae (BSFL). The results indicated that BSFL reared on a wheat bran diet exhibited significantly improved growth performance and AMP production when compared to the other three diets. AMP extracts showed enhanced antimicrobial activity and physicochemical stability, including temperatures and metal ions except Cu⁺. Moreover, AMP extracts disrupted the cell membrane and inhibited the cell cycle of Staphylococcus aureus (S. aureus), thus exhibiting antimicrobial activity. Furthermore, transcriptomic and KEGG enrichment analyses identified 509 differentially expressed genes (DEGs) related to the Toll and IMD signaling pathways. STRING and GeneMANIA analyses confirmed the association of these pathways with immune response and AMP secretion. qRT-PCR results showed elevated expression of immune genes (GNBP3, NFKBIA, GADD45, and Spz) in BSFL following S. aureus immunization, consistent with RNA-seq findings. These findings offer a valuable reference for using AMPs as antibiotic substitutes in animal feeds and highlight the need for further research on AMP purification and the synergistic regulation of protein synthesis and AMP production in BSFL.

Due to the immature gastrointestinal immune system, weaning piglets are highly susceptible to pathogens, e.g., enterotoxigenic Escherichia coli (ETEC). Generally, pathogens activate the immune cells (e.g., macrophages) and shape intracellular metabolism (including amino acid metabolism); nevertheless, the metabolic cues of tryptophan (especially melatonin pathway) in directing porcine macrophage function during ETEC infection remain unclear. Therefore, this study aimed to investigate the changes in the serotonin pathway of porcine macrophages during ETEC infection and the effect of melatonin on porcine macrophage functions. Porcine macrophages (3D4/21 cells) were infected with ETEC, and the change of serotonin pathway was analysed by reverse transcription PCR and metabolomic analysis. The effect of melatonin on porcine macrophage function was also studied with proteomic analysis. In order to investigate the effect of melatonin on bacterial clearance function of porcine macrophages during ETEC infection, methods such as bacterial counting, reverse transcription PCR and western blotting were used to detect the corresponding indicators. The results showed that ETEC infection blocked melatonin production in porcine macrophages (P < 0.05) which is largely associated with the heat-stable enterotoxin b (STb) of ETEC (P < 0.05). Interestingly, melatonin altered porcine macrophage functions, including bacteriostatic and bactericidal activities based on proteomic analysis. In addition, melatonin pre-treatment significantly reduced extracellular lactate dehydrogenase (LDH) activity (P < 0.05), indicating that melatonin also attenuated ETEC-triggered macrophage death. Moreover, melatonin pre-treatment resulted in the decrease of viable ETEC in 3D4/21 cells (P < 0.05), suggesting that melatonin enhances bacterial clearance of porcine macrophages. These results suggest that melatonin is particularly important in shaping porcine macrophage function during ETEC infection.

Antimicrobial resistance (AMR) was associated with 4.95 million deaths in 2019 and may cause 10 million deaths annually by 2050. We synthesize evidence on how the black soldier fly (Hermetia illucens) has evolved an expanded antimicrobial peptide (AMP) repertoire, which structural features drive family-specific activity, what mechanisms are directly demonstrated in H. illucens, and how AI contributes. PubMed, Web of Science, and Scopus (plus targeted Google Scholar) were searched from inception to 1 February 2026; studies were included when they reported BSF peptide identities, expression/proteomics, evolutionary analyses, quantitative activity, mechanistic assays, or BSF-focused computation, and claims were tiered as predicted, expression-supported, or experimentally supported. The literature supports 50–80 BSF AMP genes, plausibly shaped by gene duplication and balancing/diversifying selection in microbe-rich substrates, with marked induction plasticity across tissues, development, diet, and challenge. SAR is family-dependent: defensin-like peptides rely on disulfide-stabilized CSαβ folds and cationic surface topology; cecropin-like peptides on amphipathic α-helices with selectivity trade-offs; attacin-like peptides on β-architecture where charge-based heuristics are weak; and diptericin/proline-rich peptides remain largely inference-driven in BSF. Mechanistic evidence is strongest for membrane/envelope-centered killing by DLP4 and pore-associated envelope disruption by a recombinant attacin-like peptide, whereas pore geometry, oligomerization, intracellular targets, and broad “resistance-proof” claims remain unresolved. Key gaps include assay heterogeneity, salt/serum stability, selectivity/toxicity, resistance-risk testing, and limited in vivo validation, which must be addressed for credible AMR-relevant translation.