Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows

Pascottini, Osvaldo Bogado; Schyndel, Sabrina J. Van; Sprícigo, J. F. W.; Carvalho, Morel de Passos e; Mion, B.; Ribeiro, E.S.; LeBlanc, S.J.

doi:10.1038/s41598-020-62103-x

Cited by 33 publications

(35 citation statements)

References 65 publications

(81 reference statements)

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“…For the present study, 21 cows were retrospectively and deliberately selected to balance as nearly as possible for meloxicam treatment (n = 9 were treated with meloxicam and n = 12 were non-treated control), parity, and uterine health status (described below). Meloxicam treatment did not affect the uterine inflammatory status 19 nor the uterine microbiome composition 20 . This lack of effect allowed us to study the associations between reproductive tract inflammatory disease and the uterine microbiome in the postpartum period.…”

Section: Methodsmentioning

confidence: 85%

“…Five days after calving, cows were moved to a free-stall lactating pen, where they remained until the end of the experiment (35 DIM). Cows were fed for ad libitum intake and diet data are reported in Pascottini et al 19 . Milking was done twice daily in a rotary parlour.…”

Section: Methodsmentioning

confidence: 99%

“…Cows were fed for ad libitum intake and diet data are reported in Pascottini et al . 19 . Milking was done twice daily in a rotary parlour.…”

Section: Methodsmentioning

confidence: 99%

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Dynamics of uterine microbiota in postpartum dairy cows with clinical or subclinical endometritis

Pascottini

Schyndel

Sprícigo

et al. 2020

Sci Rep

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our objectives were to describe and compare the uterine bacterial composition of postpartum Holstein cows diagnosed as healthy (n = 8), subclinical endometritis (SCE; n = 8), or clinical endometritis (CE; n = 5) in the fifth week postpartum. We did metagenomic analyses of 16S rRNA gene sequences from endometrial cytobrush samples at 10, 21, and 35 days in milk (DIM), and endometrial bacterial culture at 35 DIM. Uterine bacterial composition in healthy, SCE, and CE was stable at 10, 21, and 35 DIM. Alpha and beta diversities showed a different uterine microbiome from CE compared to healthy or SCE, but no differences were found between healthy and SCE cows. At the phylum level, the relative abundance of Bacteroidetes and Fusobacteria, and at genera level, of Trueperella was greater in ce than healthy or Sce cows. Trueperella pyogenes was the predominant bacteria cultured in cows with ce, and a wide variety of bacterial growth was found in healthy and Sce cows. Bacteria that grew in culture were represented within the most abundant bacterial genera based on metagenomic sequencing. the uterine microbiota was similar between Sce and healthy, but the microbiome in cows with ce had a loss of bacterial diversity. Multiple potential mechanisms that drive reproductive tract inflammatory disease in dairy cattle have been discovered 1,2 , but questions remain about the nature and causes of the different manifestations of reproductive tract infection and inflammation. Remarkable changes in the composition of the microbiome occur in postpartum cows that develop uterine disease 3,4 , but few papers have described the dynamics of the uterine microflora in healthy postpartum cows 5,6. A robust but well-regulated postpartum uterine inflammatory response is necessary to avoid disease 7. However, in early lactation, cows experience a state of immune dysfunction concurrent with changes in metabolism associated with physiologic adaptations to support milk production. Although certain phyla and genera of bacteria are reasonably consistently associated with some forms of uterine disease, the changes of the microbiome and the host interaction with it in the progression or avoidance of disease are only partially understood. Metritis (overt systemic illness due to uterine infection, characterized by fetid vaginal discharge) and purulent vaginal discharge (PVD) without systemic signs have commonly been associated with Trueperella pyogenes using culture-dependent methods 8,9,10. Clinical endometritis (CE) is PVD with concurrent endometritis based on > 5% polymorphonuclear (PMN) neutrophils 7,11. However, with the advent of cultureindependent methods using metagenomic sequencing, it has been shown that loss of diversity and increase in abundance of Bacteroides, Porphyromonas, and Fusobacterium were associated with metritis and PVD in postpartum cows 3,4,12. Numerous studies attempted to associate the presence of bacteria with subclinical endometritis (SCE; absence of PVD and > 5% endometrial PMN), but the role of pathogenic bacteria in SCE re...

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Section: Methodsmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

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Dynamics of uterine microbiota in postpartum dairy cows with clinical or subclinical endometritis

Pascottini

Schyndel

Sprícigo

et al. 2020

Sci Rep

Self Cite

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“…Studies have shown that a certain degree of in ammation is necessary to initiate calving, assist placental expulsion and protect the dams from postpartum microbial invasion [16]. However, excessive and persistent postpartum pro-in ammatory response has been linked to increased disease risk and decreased milk production [17,18]. Metabolic changes accompanied with a pro-in ammatory state alter the homeostasis of the immune system, including IgG1/IgG2 balance, exposing dairy cows to increased disease risk in early lactation [19].…”

Section: Introductionmentioning

confidence: 99%

A Rapid Blood Test to Monitor the Immune Status Change of Dairy Cows and to Evaluate their Disease Risk during the Periparturient Period

Tsai

Hassan

Hung

et al. 2020

Preprint

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BackgroundDairy cows are at the highest risk of developing clinical and subclinical diseases and disorders in the first few weeks following parturition. During the periparturient period, from approximately 30 days before calving to 30 days postpartum, the immune system of the dairy cows undergoes a multitude of changes to prepare for parturition, colostrum production and lactation. One such change is the transfer of a large amount of immunoglobulin G proteins, especially subclass IgG1 to colostrum, leading to a reduction of IgG1 in the blood. As IgG1 and IgG2 need to maintain a balance to protect animals from intracellular and extracellular pathogens, a disruption of this balance compromises the immune protection of the animals. Rapid tests that can detect these immunological changes may be potentially useful for predicting the risk of dairy cows developing infectious diseases and other adverse health conditions following parturition. ResultsWe report here a new rapid test to detect certain immune status changes in the blood serum of dairy cows. This test uses a nanoparticle probe to evaluate the relative quantity of IgG1 and IgG2 in a sample. The nanoparticle probes are aggregated together upon interaction with bovine IgG2, while bovine IgG1 inhibits such interactions. The nanoparticle aggregates are detected by monitoring the color change of the assay solution using a handheld device. We tested the serum samples from 230 dairy cows collected during periparturient period, from 14-7 days before calving to 7-14 days postpartum. Results show that the test clearly detected an immune status change associated with IgG1/IgG2 relative quantity change around the time of parturition. Data analysis using mixed liner model in SAS (Statistical Analysis System) revealed a significant difference (P value = 0.042) in their test responses between healthy cows and cows with mastitis and/or lameness. ConclusionThe new rapid test we report here can be used to detect and monitor certain immune status change in dairy cows during the periparturient period. The test results may be potentially used to evaluate and predict the health risk of the dairy cows following parturition.

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“…In a previous study, we showed that treatment with the non-steroidal anti-inflammatory drug (NSAID) meloxicam (MEL) from 10 to 13 DIM transiently reduced haptoglobin (a marker of systemic inflammation) and improved indicators of energy metabolism (greater insulin-like growth factor-1 and glucose, and lesser β-hydroxybutyrate), and modestly increased circulating polymorphonuclear (PMN) cell function [12]. For the present analysis using samples from a subset of the same cows, the hypothesis was that metabolic changes induced by MEL would affect the uterine microbiota.…”

Section: Introductionmentioning

confidence: 99%

Effects of parity, blood progesterone, and non-steroidal anti-inflammatory treatment on the dynamics of the uterine microbiota of healthy postpartum dairy cows

Pascottini

Sprícigo

Schyndel

et al. 2020

Preprint

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12 This study evaluated the effects of treatment with meloxicam (a non-steroidal anti-inflammatory 13 drug), parity, and blood progesterone concentration on the dynamics of the uterine microbiome 14 of clinically healthy postpartum dairy cows. Seven primiparous and 9 multiparous postpartum 15 Holstein cows received meloxicam (0.5 mg/kg SC, n = 7 cows) once daily for 4 days (10 to 13 16 days in milk (DIM)) or were untreated (n = 9 cows). Endometrial cytology samples were 17 collected by cytobrush at 10, 21, and 35 DIM, from which the metagenomic analysis was done 18 using 16S rRNA gene sequence analysis. A radioimmunoassay was used to measure 19 progesterone concentration in blood serum samples at 35 DIM and cows were classified as ˃ 1 20 ng/mL (n = 10) or ≤ 1 ng/mL (n = 6). Alpha diversity for bacterial genera (Chao1, Shannon-21 Weiner, and Camargo's evenness indices) were not affected by DIM, meloxicam treatment, 22 parity, or progesterone category (P > 0.2). For beta diversity (genera level), principal coordinate 23 analysis (Bray-Curtis) showed differences in microbiome between parity groups (P = 0.01).24 There was lower overall abundance of Anaerococcus, Bifidobacterium, Corynebacterium, 25 Lactobacillus, Paracoccus, Staphylococcus, and Streptococcus and higher abundance of 26 Bacillus, Fusobacterium, and Novosphingobium in primiparous than multiparous cows (P < 27 0.05); these patterns were consistent across sampling days. Bray-Curtis dissimilarity did not 28 differ by DIM at sampling, meloxicam treatment, or progesterone category at 35 DIM (P > 0.5).29 In conclusion, uterine bacterial composition was not different at 10, 21, or 35 DIM, and 30 meloxicam treatment or progesterone category did not affect uterine microbiota in clinically 31 healthy postpartum dairy cows. Primiparous cows presented a different composition of uterine 32 bacteria than multiparous cows. The differences in microbiome associated with parity might be 33 attributable to changes that occur consequent to the first calving, but this hypothesis should be 34 investigated further.

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Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows

Cited by 33 publications

References 65 publications

Dynamics of uterine microbiota in postpartum dairy cows with clinical or subclinical endometritis

Dynamics of uterine microbiota in postpartum dairy cows with clinical or subclinical endometritis

A Rapid Blood Test to Monitor the Immune Status Change of Dairy Cows and to Evaluate their Disease Risk during the Periparturient Period

Effects of parity, blood progesterone, and non-steroidal anti-inflammatory treatment on the dynamics of the uterine microbiota of healthy postpartum dairy cows

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