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Background:
Subacute ruminal acidosis (SARA) is a metabolic disease in high-producing dairy cattle, and is accompanied by rumenitis. However, the mechanism of rumenitis remains unclear. Therefore, the aim of this study was to investigate the molecular mechanism of rumenitis in dairy cows with SARA.
Results:
The results showed that SARA cows disp...
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Citations
... Reduced feed intake, poor body condition score, and diarrhea were reported as main clinical signs in subacute ruminal acidosis (Lorentz 2015). The rumen fluid of affected goats showed lowered pH, higher TVFA, propionate, butyrate, ammonia nitrogen, lactate and endotoxin similar to that reported by Owens et al. (1998) and Zhao et al. (2018). The serum of the affected animals had elevated BUN and Urea, Stefanska et al. (2020) also had reported that herds testing positive for SARA exhibited elevated concentrations of BUN (16.2 vs. 10.1 mg/dL), in this study BUN as high as 20.1 was observed. ...
Rumen cud transfaunation re-establishes rumen micro environment and improves fermentation in recipient animals affected with digestive disorders. Preserving rumen cud or fluid will increase its availability for the treatment of rumen fermentation disorders, without having to maintain donor animals. Rumen fluid collected from healthy goats, fed standard ration having roughage 70% and concentrate 30%, was lyophilized (prefreezing -80 °C, 48 h; lyophilization -45 °C, 32 h) using 5% glycerol as cryoprotectant. The 16 S metagenome analysis of the lyophilized rumen fluid (LRF) revealed an abundance of Prevotella (33.2%). Selenomonas ruminantium (1.87%) and Megasphaera elsdenii (0.23%) were also present. Twenty-four goats having history of high grain feeding and exhibiting clinical symptoms of rumen fermentation disorders were randomly distributed into either one of the two treatment groups viz., T1 = oral administration of LRF 31 g/animal/day and T2 = oral administration of sodium bicarbonate (SB) 15 g/animal/day. Post intervention LRF and SB, improved animal body condition, feed intake, fecal consistency, elevated the ruminal pH at 48 h, reduced propionate and lactate at 48 h, reduced total volatile fatty acids (TVFA) and ammonia nitrogen at 24 h. Significant reduction in serum blood urea nitrogen (BUN) and urea levels were observed even from 24 h post intervention irrespective of the treatments. LRF significantly improved acetate and decreased propionate production compared to SB. LRF at 7.5% (v/v) can thus be used to counteract ruminal fermentation disorders in goats sequel to high grain ration.
... In bovine, gram-negative ruminal bacteria are the main source of LPS in the rumen [50]. Cows diagnosed with SARA often exhibit low pH levels and elevated concentrations of free LPS in the rumen, which if not treated properly can trigger a proin ammatory response [51,52]. When the ruminal epithelium is in amed, a decrease in barrier function increases the chance for pathogenic substances, including LPS, to enter the blood circulation and negatively affect other organs such as the liver, udder and uterus [6,53,54]. ...
Background：In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against subacute ruminal acidosis (SARA)-induced inflammation and the underlying mechanisms are unknown.
Results：Eight ruminally cannulated Holstein cows in mid-lactation were randomly assigned to either a low-concentrate (40%) diet (CON) or a high-concentrate (60%) diet (HC) for 3 weeks to induce SARA. Cows with SARAhad greater concentrations of tumor necrosis factor (TNF)-α and interleukin-6, and epithelium showed histological signs of damage. Lipopolysacharide was used in vitro to simulate the inflammatory damage caused by SARA uisng immortalized bovine rumen epithelial cells (BREC). Increased phosphorylation of IκBα and nuclear factor kappa-B (NF-κB) p65 due to 10 µg/mL LPS for 6 h revealed a successful chronic inflammatory response in BREC. Pre-treatment of BREC with 50 µM EGCG for 6 h before LPS challenge promoted the degradation of NLR family pyrin domain containing 3 (NLRP3) inflammasome through activation of autophagy, which further repressed activation of NF-κB pathway targeting Toll-like receptor 4(TLR4). The ECGG also upregulated tight junction (TJ) protein expression upon incubation with LPS.
Conclusions：Subacute ruminal acidosis causes ruminal epithelium injury and systemic inflammation in dairy cows. However, the anti-inflammatory effects of EGCG help preserve the integrity of the epithelial barrier through activating autophagy when BREC are exposed to LPS. Thus, EGCG could potentially serve as an effective therapeutic agent for SARA-associated inflammation.
... Microorganisms in the rumen not only play a key role in animal digestion and absorption but also play an important role in host immune response and body health [18][19][20]. A large number of studies on cows have shown that ruminal dysbiosis could lead to metabolic changes in rumen and other parts of the digestive tract, causing a large number of microorganisms to release toxins into gastrointestinal lumen, triggering various systemic inflammations and directly affecting the health of next generation [21]. Therefore, from the perspective of ruminant reproductive health, strengthening rumen health is particularly important [22]. ...
The effects of isochlorogenic acid (ICGA) on ewes rumen environment, microbial diversity, and immunity at different physiological stages (estrus, pregnancy and lactation) were studied in this experiment. Twenty healthy female Hu lambs of 1.5 months with similar body weight (17.82 ± 0.98 kg) and body condition were selected and randomly divided into two groups: the control group (CON) and the ICGA group (ICGA). The lambs of CON were fed a basal diet, while the lambs of ICGA were supplemented with 0.1% ICGA based on the basal diet. Lambs rumen fermentation characteristics, microbial diversity and immunity at estrus, pregnancy, and lactation stages were determined and analyzed, respectively. The results showed that the rumen pH in CON increased first and then decreased as lambs grew (p < 0.05). However, it showed the opposite change in ICGA. The content of ammonia nitrogen (NH3-N) showed the highest at estrus stage in both groups, but it was significantly higher in ICGA than that in CON (p < 0.05). The Acetic acid/propionic acid (A/P) ratio at estrus stage and the volatile fatty acids (VFAs) at pregnancy stage in ICGA were significantly higher than those of the CON (p < 0.05). The 16S rDNA sequencing analysis showed that the Shannon, Chao 1 and ACE indexes of the ICGA were significantly higher than those of the CON both at estrus and lactation stages (p < 0.05), while they showed higher at the pregnancy stage in CON (p > 0.05). Principal component analysis (PCA) showed that there were significant differences in rumen microorganism structure between CON and ICGA at all physiological stages (p < 0.01). At the phylum level, compared with the CON, Firmicutes relative abundance of three physiological stages decreased (p > 0.05) while Bacteroidota increased (p > 0.05). The relative abundance of Synergistota at estrus stage and Patescibacteria at the lactation stage increased significantly too (p < 0.05). At the genus level, compared with the CON, the relative abundance of Prevotella at three stages showed the highest (p > 0.05), while the relative abundance of Succiniclasticum, unclassified_Selenomonadaceae and Rikenellaceae_RC9_gut_group showed different abundances at different physiological stages in ICGA. Compared with the CON, the lambs of the ICGA showed higher blood IgG, IgM, and TNF- α contents at three physiological stages and higher IL-6 contents at pregnancy stage (p < 0.05). Conclusion: Adding ICGA could regulate ewes rumen fermentation mode at different physiological stages by increasing rumen NH3-N at estrus, VFAs at pregnancy, and the ratio of A/P at lactation. It optimizes rumen microbial flora of different physiological stages by increasing Bacteroidota relative abundance while reducing Firmicutes relative abundance, maintaining rumen microbial homeostasis at pregnant stage, increasing the number of beneficial bacteria in later lactating and ewes blood immunoglobulins content at three physiological stages.
... Ho w e v er, these r elativ el y r a pid and pr ofound modifications can alter the integrity of the epithelial barrier, compromising the structure of tight junctions and desmosomes , Liu et al. 2013, McCann et al. 2016. At the same time, the above mentioned dietary challenges may induce changes in microbiota composition and function, leading to production of other microbederived compounds with proinflammatory properties such as biogenic amines, lipopol ysacc harides (LPS) or lipoteic hoic acid, whic h can alter epithelial inflammation pathways resulting in both local and systemic inflammation (Zhang et al. 2016, Zhao et al. 2018. These alterations of the microbial composition and activity create a perturbation of the ruminal homeostasis, defined as dysbiosis (Sommer et al. 2017 ). ...
Diets rich in readily fermentable carbohydrates primarily impact microbial composition and activity, but can also impair the ruminal epithelium barrier function. By combining microbiota, metabolome, and gene expression analysis, we evaluated the impact of feeding a 65% concentrate diet (HG) for four weeks, with or without a phytogenic feed additive (PFA), on the rumen ecosystem of cattle. The breaking point for rumen health seemed to be the second week of HG diet, with a dysbiosis characterized by reduced alpha diversity. While we did not find changes in histological evaluations, genes related with epithelial proliferation (IGF-1, IGF-1R, EGFR and TBP) and ZO-1 were affected by the HG feeding. Integrative analyses allowed us to define the main drivers of difference for the rumen ecosystem in response to a HG diet, identified as ZO-1, MyD88 and genus Prevotella 1. PFA supplementation reduced the concentration of potentially harmful compounds in the rumen (e.g. dopamine and 5-aminovaleric acid) and increased the tolerance of the epithelium towards the microbiota by altering the expression of TLR-2, IL-6 and IL-10. The particle associated rumen liquid microbiota showed a quicker adaptation potential to prolonged HG feeding compared to the other microenvironments investigated, especially by the end of the experiment.
... Another area of problem for definition of the so-called subacute ruminal acidosis is related to the way it was induced experimentally. Adding various amounts of pellets of highly fermentable grains 22 , or alfalfa 24 to the diet, restricted feeding followed with grain challenge 32 , or sudden raising of concentrate level 33 were regular ways of inducing the disease and depending on these ways the consequences were varied. Table 2 summarized some of these protocols and indicated their variable responses on rumen parameters, dry matter intake, milk fat percentage, and inflammatory response in the blood (acute phase proteins). ...
Subacute ruminal acidosis can be defined as a depression of rumen pH, which affects animal health and production. Although researchers have tried to find a solution for this disorder, it is a prevalent problem that causes considerable losses in commercial dairy cow production. This review aims to reveal critical points in current knowledge about subacute ruminal acidosis and suggest solutions for future research. The first challenging issue in subacute ruminal acidosis is the diagnosis method of this disorder, which requires appropriate statistical evaluation and modeling. In addition, biological factors should be considered to define subacute ruminal acidosis since some roles have recently been observed for different CO2 species in the rumen as a direct cause of the events. These CO2 species are sometimes more accurate than rumen pH in explaining the decrease in feed intake, milk yield, milk fat percentage, and inflammation responses. In the future, the measuring of the CO2 species in the rumen may be a replacement for pH measurement or become a factor that can greatly explain ruminal acidosis. Compared to basic methods, another challenging point is the reliability of rumen pH measurements as well as the accuracy of newly developed sensors. The reticular pH with current boluses could be measured by monitoring cows on-farm or a large number of animals in research. In conclusion, a thorough definition and precise application of new measurement devices can reveal some unknown factors for subacute ruminal acidosis in dairy cows.
... Investigators have revealed that the low rumen pH of SARA induced by SCFAs and lactic acid accumulation leads to gram-negative bacteria death, lysis, and lipopolysaccharide (LPS) release, thereby destroying the rumen epithelium barrier integrity by triggering an inflammatory response in the rumen epithelium, then causing systemic inflammation [4][5][6]. Specifically, research has found that a high concentration of ruminal LPS, a characteristic of SARA, facilitates the activation of the NF-κB and MAPKs inflammatory pathways and promotes pro-inflammation cytokines production in the rumen epithelium [7,8]. ...
Subacute ruminal acidosis (SARA) is a common nutritional metabolic disease in ruminants that causes significant economic losses to dairy farming. Strontium (Sr) is known to be involved in bone metabolism and exhibits potent anti-inflammatory effects. To evaluate the effect of Sr on inflammation in bovine ruminal epithelial cells, a model of LPS-induced inflammation was established in this study, and the cell viability of bovine ruminal epithelial cells was measured using CCK-8. The production of pro-inflammatory cytokines was measured by ELISA and real-time PCR, respectively. The related proteins of the TLR4/MyD88/NF-κB pathway were assayed through Western blotting, and the fluorescence of p-p65 and p-IκB were assayed by immunofluorescence. Molecular docking of Sr and TLR4/MyD88/NF-κB pathway-related proteins was performed using MIB2 (http://bioinfo.cmu.edu.tw/MIB2/). Results showed that after treatment for 24 h, the cell viability was decreased at the high concentration of Sr (≥ 10 mmol/L). Sr significantly decreased the production of TNF-α, IL-1β, and IL-6, downregulated the related proteins expression of the TLR4/MyD88/NF-κB pathway, and reduced the fluorescence levels of p-p65 and p-IκB. The NF-κB pathway inhibitor PDTC and molecular docking further revealed that Sr reduced LPS-induced pro-inflammatory cytokines production via the TLR4/MyD88/NF-κB pathway. These results suggest that Sr reduces LPS-induced pro-inflammatory cytokines production via the TLR4/MyD88/NF-κB pathway, thereby exerting an anti-inflammatory effect in bovine ruminal epithelial cells, providing a basis for Sr in the treatment of bovine rumen acidosis disease.
... The results showed that the phosphorylation levels of P38 MAPK, ERK, JNK, and NF-κB p65 in the rumen epithelium were increased in the SARA group, and the phosphorylation levels in the rumen abdominal sac were higher than those in the dorsal sac. Studies have shown that the overactivation of NF-κB and MAPKs can signi cantly augment the expression of in ammatory cytokines, suggesting that the LPSinduced release of in ammatory factors in the rumen epithelium might be mediated by these pathways [51]. A high concentrate diet can upregulate the expression of IL-1β, IL-2, IL-22, and other in ammatory factors [52]. ...
Background
The long-term feeding of high-concentrate diets to ruminants will damage the structure and function of their rumen flora, leading to changes in the gastrointestinal patterns of digestive nutrients and metabolic factors, and causing subacute rumen acidosis (SARA).
Methods
28 small-tailed Han sheep were randomly selected and divided into three groups, namely the control group, SARA model group, and treatment group. The control group was fed low concentrate fodder, the model group was fed high concentrate fodder, and the treatment group was fed the HC first and then the LC after successfully establishing the model (n = 9).
Results
SARA-model sheep had high concentrations of lipopolysaccharide (LPS) in their rumen fluid and blood, whereas tumor necrosis factor-α (TNF-α) was significantly elevated in the rumen fluid, with no difference in the blood. The levels of inflammation-related proteins, namely cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), TNF-α, and Toll-like receptor-4 (TLR-4), were significantly increased in the rumen epithelium of SARA-model sheep. Phosphorylation levels of nuclear transcription factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in the SARA group were significantly higher than those in the control and treatment groups. The phosphorylation levels of NF-κB and MAPKs inflammatory mediators and protein levels of inflammatory factors in the SARA-model sheep rumen abdominal sac were significantly higher than those in the rumen dorsal sac. The expression of tight junction proteins ZO-1, occludin, claudin-1 and claudin-4 decreased compared with that in the control group. The expression of light chain 3 (LC-3) increased in rumen epithelium of SARA sheep, while the trend of autophagy substrate sequestosome-1 (P62) was opposite to that of LC-3.
Conclusions
These results indicate that SARA leads to a high concentration of ruminal LPS, which significantly increases the expression and synthesis of pro-inflammatory cytokines in the rumen epithelium, through the over-activation of NF-κB and MAPK inflammatory pathways, thereby inducing rumenitis, damaging the integrity of rumen epithelium; moreover, damage to the rumen abdominal sac is more serious than that to the rumen dorsal sac. In the process of rumen gastritis, autophagy is involved in the regulation and inhibition of the inflammatory response.
... Although feeding an HC diet can improve economic efficiency in the short term, longterm feeding can lead to a series of nutritional metabolic diseases, the most important of which is subacute rumen acidosis (SARA) (1), defined as a rumen pH of 5.0-5.5 for a duration exceeding 3 h per day (2). When rumen pH remains low for a long time, Gramnegative bacteria in rumen lyse and release large amounts of lipopolysaccharide (LPS) (3), resulting in mammary gland tissue damage in dairy cows (4). ...
... (1) LPS concentration gradient treatment. To study the effects of different concentrations of LPS on autophagy-related genes and proteins in BMECs, the cells were treated with different concentrations of LPS (2,4,8,16, and 20 mg/ml) for 3 h. The mRNA and protein expression of ATG5, p62, and LC3 and the fluorescence intensity of p62 and LC3 were determined to identify the optimal concentration of LPS. ...
Introduction
Calmodulin-dependent protein kinase β (CaMKKβ) is closely related to Ca²⁺ concentration. An increase in Ca²⁺ concentration in the cytoplasm activates CaMKKβ, and activated CaMKKβ affects the activities of AMPK and mTOR and induces autophagy. A high-concentrate diet leads to Ca²⁺ disorder in mammary gland tissue.
Objectives
Therefore, this study mainly investigated the induction of mammary gland tissue autophagy by a high-concentrate diet and the specific mechanism of lipopolysaccharide (LPS)-induced autophagy in bovine mammary epithelial cells (BMECs).
Material and Methods
Twelve mid-lactation Holstein dairy cows were fed with a 40% concentrate diet (LC) and a 60% concentrate diet (HC) for 3 weeks. At the end of the trial, rumen fluid, lacteal vein blood, and mammary gland tissue were collected. The results showed that the HC diet significantly decreased rumen fluid pH, with a pH lower than 5.6 for more than 3 h, indicating successfully induction of subacute rumen acidosis (SARA). The mechanism of LPS-induced autophagy in BMECs was studied in vitro. First, the cells were divided into a Ctrl group and LPS group to study the effects of LPS on the concentration of Ca²⁺ and autophagy in BMECs. Then, cells were pretreated with an AMPK inhibitor (compound C) or CaMKKβ inhibitor (STO-609) to investigate whether the CaMKKβ–AMPK signaling pathway is involved in LPS-induced BMEC autophagy.
Results
The HC diet increased the concentration of Ca²⁺ in mammary gland tissue and pro-inflammatory factors in plasma. The HC diet also significantly increased the expression of CaMKKβ, AMPK, and autophagy-related proteins, resulting in mammary gland tissue injury. In vitro cell experiments showed that LPS increased intracellular Ca²⁺ concentration and upregulated protein expression of CaMKKβ, AMPK, and autophagy-related proteins. Compound C pretreatment decreased the expression of proteins related to autophagy and inflammation. In addition, STO-609 pretreatment not only reversed LPS-induced BMECs autophagy but also inhibited the protein expression of AMPK, thereby alleviating the inflammatory response in BMECs. These results suggest that inhibition of the Ca²⁺/CaMKKβ–AMPK signaling pathway reduces LPS-induced autophagy, thereby alleviating inflammatory injury of BMECs.
Conclusion
Therefore, SARA may increase the expression of CaMKKβ by increasing Ca²⁺ levels and activate autophagy through the AMPK signaling pathway, thereby inducing inflammatory injury in mammary gland tissue of dairy cows.
... Grain-based SARA increases ruminal and peripheral bacterial endotoxin concentrations [51]. Rumen endotoxin can be released into the peripheral circulation causing systemic inflammation, and its concentration is negatively correlated with plasma TCHO concentration [52,53]. In the present study, the TCHO level was reduced in cows fed a HG diet. ...
Background:
High-grain (HG) diets affect lipid metabolism in the liver and mammary tissue of dairy cows, but its effects on muscle and adipose tissue have not been wide evaluated. Thus, the aim of this study is to clarify this issue.
Methods:
Twelve Holstein cows were randomly divided into two groups: conventional diet group (CON, n = 6) and the HG diet group (n = 6). On day 7 of week 4, rumen fluid was sampled to measure pH, milk was sampled to measure components, and blood was sampled to measure biochemical parameters and fatty acid composition. After the experiment, cows were slaughtered to collect muscle and adipose tissue for fatty acid composition and transcriptome analysis.
Results:
HG feeding decreased the ruminal pH, milk's fat content and long-chain fatty acid proportion (P < 0.05) and increased the proportion of short- and medium-chain fatty acids in the milk (P < 0.05) as compared with CON diets. The concentrations of blood cholesterol, low-density lipoprotein, and polyunsaturated fatty acids in the HG cows were lower than those in CON cows (P < 0.05). In muscle tissue, HG feeding tended to increase the triacylglycerol (TG) concentration (P < 0.10). Transcriptome analysis revealed changes in the biosynthesis of the unsaturated fatty acids pathway, the regulation of lipolysis in the adipocytes pathway, and the PPAR signalling pathway. In adipose tissue, HG feeding increased the concentration of TG and decreased the concentration of C18:1 cis9 (P < 0.05). At the transcriptome level, the fatty acid biosynthesis pathway, linoleic acid metabolism pathway, and PPAR signalling pathway were activated.
Conclusion:
HG feeding leads to subacute rumen acidosis and a decreased milk fat content. The fatty acid profiles in the milk and plasma of dairy cows were changed by HG feeding. In muscle and adipose tissue, HG feeding increased TG concentration and up-regulated the expression of genes related to adipogenesis, while down-regulated the expression of genes related to lipid transport. These results complement our knowledge of the fatty acid composition of muscle and adipose tissue in dairy cows and expand our understanding of the mechanisms by which HG diets affect lipid metabolism in muscle and adipose tissue.
... Isoprostanes (IsoP) are also important biomarkers of lipid peroxidation damage because they form when ROS oxidizes arachidonic acid. Indeed, IsoP was found in the blood and milk of dairy cows during periods of high oxidative stress, such as the peripartum and mastitis periods [136]. ...
Oxygen is a key element involved in a variety of vital physiological reactions in aerobic organisms, including those produced in the electron transport chain, hydroxylation, and oxygenation. Reactive oxygen species and reactive oxygen nitrogen species (ROS/RONS) are naturally formed as by-products from these previously mentioned processes and reactions involving the O2 molecules. Under healthy conditions, the harmful effects of ROS/RONS in the organisms are controlled by antioxidants, molecules of enzymatic or non-enzymatic nature, able to prevent, retard, or eliminate oxidative damage. Nevertheless, when ROS/RONS production exceeds the antioxidant capacity of one organism, oxidative stress emerges, leading to the apparition of many diseases, some of which can depict significant losses in the field of animal production. Thereby, looking for increasing animal productivity, procedures to mitigate the effects of oxidative stress on living organisms are tested in laboratory animal models, and the obtained results are used to develop strategies that avoid oxidative stress in farm animals either invertebrates (mollusks and crustacean species) or vertebrates (fish, birds, and mammals). In this chapter, oxidative stress will be addressed from the field of animal health and welfare and its impact on animal production, presenting some strategies, studies conducted, and recent perspectives to mitigate the effects of oxidative stress and improve the productivity indicators in farm animals.
