Particulate matter in poultry house on poultry respiratory disease: A systematic review.

Ammonia in Poultry House PM Poses a Respiratory Health Hazard

Ammonia is the most alkaline harmful irritant gas in the poultry house. The combination of airborne ions and volatile particles of ammonia crystals in urine is an essential component of PM_2.5 in poultry houses. Ammonia is the most hazardous toxic gaseous particulate pollutant in poultry houses. Due to the low ventilation frequency in winter, a high concentration of ammonia is very common in intensive poultry houses (Naseem and King, 2018). When the ammonia content in the poultry house rises to a certain value, a strong ammonia smell will be smelled. Due to the limitation of the detection equipment, the ammonia compounds carried in PM_2.5 cannot be detected. This situation is often overlooked. High concentrations of ammonia, and ammonia compounds in poultry houses, have been reported to cause multiple organ damage in poultry. Studies have focused on observing immune cells and organs (An et al., 2019; Zhao et al., 2020; Zhou et al., 2020; Li et al., 2021; Zhou et al., 2021; Zhou et al., 2021). However, little is known about the mechanism of respiratory poisoning by ammonia and ammonia compounds. It is generally accepted that the absorption of exogenous ammonia in poultry first causes the breakdown of mucosal barriers in the respiratory tract and lungs, which causes immune imbalance and leads to the development of respiratory inflammation (Wang et al., 2022). Sustained exposure of broilers to ammonia revealed a significant elevation of inflammatory markers, activation of the nuclear transcription factors κB (NFκB) pathway, apoptosis, and disturbed immune status in the trachea (Shi et al., 2019).In addition, autolysosomes were induced by ammonia exposure in the ultrastructure of tracheal tissue, and aberrant expression of the upstream genes mir-2188-5p and circ-ifnlr1 were detected (Zhang et al., 2022). Increased reactive oxygen species (ROS) levels, reduced antioxidant capacity, and high expression of apoptotic factors can be detected in the lungs of broilers (Bai et al., 2021).In addition to disrupting the mucosal barrier and causing immune disorders, ammonia may cause respiratory inflammation by perturbing microbial distribution and species changes (Liu et al., 2020; Zhou et al., 2021; Wang et al., 2022). During the healthy growth of broilers, the respiratory microbiota changes dynamically with the broilers growing. This dynamic change and the growth environment of broilers have a strong correlation, especially with the quality of air (Chen et al., 2021).

Microorganisms in Poultry Houses Pose a Respiratory Health Hazard

Pathogenic bacteria, endotoxins, and allergens are carried in PM. These factors often lead to respiratory diseases, including chronic bronchitis, asthma, and dust poisoning syndrome (Hamid et al., 2018; Stuper-Szablewska et al., 2018). In a poorly ventilated poultry house, many microorganisms were attached to the PM_2.5 in the poultry house and increased with higher PM concentrations (Nimmermark et al., 2009). Because of the high temperature and humidity environment in the poultry house, saprophytic bacteria dominated the microorganisms in the PM of the poultry house. High concentrations of microbes and metabolites negatively affect the structure and defense function of the respiratory mucosa. Pathogenic and conditionally pathogenic microbes can cause immunotoxin, allergic effects, and even infectious diseases (Chmielowiec-Korzeniowska et al., 2021). In poultry houses, bacteria that pose a threat to the health of poultry are Chlamydia spp., Staphylococcus aureus, Listeria spp., Streptococcus spp., and a variety of Salmonella spp., which can infect the respiratory and lung, causing interstitial pneumonia, airway inflammation, and a range of respiratory diseases (Dai et al., 2020). In addition, the resistance of bacteria has increased due to antibiotic usage problems, and the effectiveness in preventing and treating diseases has declined (Nhung et al., 2017). Gallinaceous fungi, Aspergillus, Scopulariopsis, Wallemia, and Fusarium, were abundant in the PM of the poultry house. These species are found in plant raw materials and feces. Since fungal spores readily reach the lower respiratory tract with PM, they can cause allergic reactions, respiratory inflammation, and the production of pneumonia (Zukiewicz-Sobczak et al., 2013).

Besides that, microbes’ residues and metabolites cause immunotoxicity in the lung immune system. Endotoxin is a cell wall component of gram-negative bacteria and is made of lipopolysaccharide (LPS). After binding with PM, it diffuses into the environment. When LPS binds to LPS binding protein (LBP) and subsequently to CD14, which is then recognized by toll-like receptor (TLR) 4, they activate the innate immune system. LPS binding to the CD14 / TLR4 complex activates macrophages and produces proinflammatory cytokine. Broilers, at high concentrations of LPS, exhibit respiratory and pulmonary tissue lesions and pulmonary arterial hypertension, decreased in vivo immune protein binding capacity, higher interferon expression, and TLR4 expression (Roque et al., 2015; van der Eijk et al., 2022). Mycotoxins produced by fungi in the PM of poultry houses pose hazards to poultry gastrointestinal, respiratory, and immune systems and, under continuous exposure, can even cause death. Of particular note, mold produces β- 1,3-glucan and is an essential factor in causing pneumonia in broilers (Dutkiewicz et al., 2011; Zhang et al., 2021). A study of broiler exposure to PM in poultry houses directly unraveled the impact of microbial and their metabolite perturbations due to PM on lung injury in broilers. Using a combined microbiome and metabolome analysis approach, lung injury and microbial community disruption in broilers were observed, along with a strong correlation in microbial metabolites (Shen et al., 2022). Similar conclusions emerged from other studies in which exposure of rats to PM_2.5 impaired lung microbiome and immune homeostasis, manifested by a significant increase in the ability of PM to phagocytose bacteria by macrophages and induced changes in immunoglobulin levels (Li et al., 2020).

Alveolar macrophages-ROS pathway

Inhaled PM_2.5 can first stimulate alveolar macrophages to produce proinflammatory factors, which stimulate epithelial cells, endothelial cells, and fibroblasts of the alveoli to secrete cytokines and adhesion factors and induce inflammatory cell aggregation, triggering an inflammatory response (Tang et al., 2019; Marcella et al., 2022).

From limited reports, we know that intracellular ROS levels and expression levels of pyroptosis-related genes (NLRP3, IL-18, IL-1B) and necroptosis-related genes (RIPK3) are significantly enhanced in broilers primary alveolar epithelial cells exposed to PM_2.5 (Dai et al., 2019). PM can stimulate the respiratory tissue cells to produce ROS (Choi et al., 2022; Marques et al., 2022), and it can activate redox-sensitive signal transduction pathways, such as mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase / protein kinase B (PI3K / Akt) pathways (Li et al., 2021; Xu et al., 2021; Zhu et al., 2022). MAPKs comprise a group of serine/threonine protein kinases (c-Jun NH2 terminal kinase, JNK; extracellular signal-regulated kinases, ERKs; stress-activated protein kinase, p38) that can be activated upon stimulation by extracellular stressors, regulate signal transduction from the cell surface to the nucleus, and ultimately lead to upregulated expression of proinflammatory factors causing cellular inflammatory responses (Ronkina and Gaestel, 2022). Studies have reported that PM can induce alveolar macrophages to produce excessive ROS, which in turn activate MAPKs and induce upregulation of the expression of the transcriptional activator AP-1, inducing cellular inflammatory responses(Ko et al., 2015; Nath et al., 2018; Chen et al., 2022). Diesel exhaust particles induce ROS production in human tracheal epithelial cells, activating ERK1 / 2 and p38, activating the downstream NFκB pathway, ultimately evoking the cell to undergo an inflammatory response (Jiang et al., 2020).

Calcium ion (Ca² +) is indispensable for maintaining life activities and plays a vital role in the body’s immune function (Chan et al., 2015). It has been found that oxidative stress in respiratory epithelial cells caused by PM stimulates Ca²⁺ release from the ER and regulates the NFκB expression, which promotes the upregulation of inflammatory factors expression (Xing et al., 2016; Yang et al., 2020; Jheng et al., 2021; Song et al., 2022).

TLR4-NF-κB pathway

From another study, we know the relevant mechanism of PM_2.5 toxicity on human alveolar basal epithelial (A549) cells in poultry houses. TLR4-NF-κB pathway mediates inflammation in A549 cells induced by PM_2.5 in poultry houses; Nrf2 decreases NF-κB by inhibiting oxidative stress and endoplasmic reticulum stress expression, thereby slowing inflammation; Autophagy by promoting NF-κB expression, while suppressing Nrf2 expression promotes inflammation (Dai et al., 2019). Co-stimulation of mouse lung tissue with PM_2.5 in the poultry house and carrier Pseudomonas aeruginosa upregulated interleukin (IL) – 6, IL-8, TNF α via the nucleus- α The expression levels, which in turn regulate NF-κB expression (Li et al., 2020). In addition, porcine house PM induces immune responses by activating the TLR4 / MAPK / NF-κB pathway and the NLRP3 inflammasome in alveolar macrophages (Tang et al., 2019). TLRs are pattern recognition receptors expressed on the surface of innate immune cells. They can recognize one or more pathogen-associated molecular patterns, which play a role in innate and acquired immune systems. Airborne particulate pollutants have been found to activate the cellular pattern recognition receptors TLR2 and TLR4. Myeloid differentiation factor 88 (MyD88) and TIR domain adapter protein (TRIP), which are adaptor proteins for all TLRs, are potential downstream proteins whose expression is triggered by particle exposure (Shoenfelt et al., 2009; Ryu et al., 2022). Lung macrophages, upon stimulation by PM, TLR4 associates with trip-related adaptor molecule binding recruits TRIP, which activates p38, causing up-regulation of the expression of downstream inflammatory factors, ultimately leading to inflammatory responses in cells (Tang et al., 2019). Disturbances in the microbial flora and metabolites caused by PM_2.5 in the respiratory tract and lungs may also be a predisposing factor leading to respiratory inflammation. However, further studies are needed to reveal whether changes in the distribution and quantity of microbiota precede or whether inflammation is produced.

Dysbiosis

Mice exposed to PM_2.5 reduced the abundance and composition of lung and intestinal microflora and found different degrees of metabolic abnormalities in BALF and serum (Ran et al. 2021). In another experiment, it was found that PM_2.5 could change the composition and abundance of pulmonary microbial flora and cause inflammation and oxidative stress by transplanting the disordered pulmonary flora into the nose (Wang et al. 2022). In addition, after PM_2.5 disturbs the lung’s microbial composition, it increases mice’s susceptibility to pneumococcus and exacerbates the deterioration of lung disease (Chen et al. 2020). Interestingly, a probiotic intervention was found to have preventive effects on the occurrence of PM_2.5-induced pathological injury. The mechanism was associated with inhibiting inflammatory response, regulating Th17/Treg balance and maintaining intestinal internal environment stability (Wu et al. 2022).

These studies showed that exposure to ambient PM_2.5 caused not only dysbiosis in the lung but also significant systemic and local metabolic alterations. Alterations in lung microbiota were strongly correlated with metabolic abnormalities. They suggest the potential roles of lung microbiota in PM_2.5-caused metabolic disorders.