Transcriptome Differences Suggest Novel Mechanisms for Intrauterine Growth Restriction Mediated Dysfunction in Small Intestine of Neonatal Piglets

Huang, Shimeng; Wu, Zhenhua; Yuan, Xiongkun; Li, Na; Li, Tiantian; Wang, Junjun; Levesque, Crystal L; Feng, Cuiping

doi:10.3389/fphys.2020.00561

Cited by 13 publications

(11 citation statements)

References 76 publications

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“…The levels of apoptosis in the colon tissues were detected by TUNEL staining according to the instructions provided as previously described. 83 The DAPI blue nuclei with the same label were selected as the total cells, and the TUNEL positive cell number per field of intestinal epithelial cells was analyzed. Cell apoptosis was observed by green fluorescence microscopy (200 × magnification).…”

Section: Methodsmentioning

confidence: 99%

Cohousing-mediated microbiota transfer from milk bioactive components-dosed mice ameliorate colitis by remodeling colonic mucus barrier and lamina propria macrophages

Liu

Huang

et al. 2021

Gut Microbes

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Human milk oligosaccharides (HMOs) and milk fat globule membrane (MFGM) are highly abundant in breast milk, and have been shown to exhibit potent immunomodulatory effects. Yet, their role in the gut microbiota modulation in relation to colitis remains understudied. Since the mixtures of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) perfectly mimic the properties and functions of HMOs, the combination of MFGM, FOS, and GOS (CMFG) has therefore been developed and used in this study. Here, CMFG were pre-fed to mice for three weeks to investigate its preventive effect on dextran sodium sulfate (DSS) induced colitis. Moreover, CMFG-treated and vehicle-treated mice were cohoused to further elucidate the preventive role of the gut microbiota transfer in colitis. At the end of the study, 16S rDNA gene amplicon sequencing, short-chain fatty acids (SCFAs) profiling, transcriptome sequencing, histological analysis, immunofluorescence staining and flow cytometry analysis were conducted. Our results showed that CMFG pre-supplementation alleviated DSS-induced colitis as evidenced by decreased disease activity index (DAI) score, reduced body weight loss, increased colon length and mucin secretion, and ameliorated intestinal damage. Moreover, CMFG reduced macrophages in the colon, resulting in decreased levels of IL-1β, IL-6, IL-8, TNF-α, and MPO in the colon and circulation. Furthermore, CMFG altered the gut microbiota composition and promoted SCFAs production in DSS-induced colitis. Markedly, the cohousing study revealed that transfer of gut microbiota from CMFG-treated mice largely improved the DSS-induced colitis as evidenced by reduced intestinal damage and decreased macrophages infiltration in the colon. Moreover, transfer of the gut microbiota from CMFG-treated mice protected against DSS-induced gut microbiota dysbiosis and promotes SCFAs production, which showed to be associated with colitis amelioration. Collectively, these findings demonstrate the beneficial role of CMFG in the gastrointestinal diseases, and further provide evidence for the rational design of effective prophylactic functional diets in both animals and humans.

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Section: Methodsmentioning

confidence: 99%

Cohousing-mediated microbiota transfer from milk bioactive components-dosed mice ameliorate colitis by remodeling colonic mucus barrier and lamina propria macrophages

Liu

Huang

et al. 2021

Gut Microbes

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“…LPA is known to be associated with metabolic diseases ( 31 ) and may be involved in the pathogenesis of PE ( 14 – 17 ). BTNL3 has also been reported to have a possible role in intestinal metabolism and inflammation in neonates with intrauterine growth restriction ( 32 ). Our study found that copies of both LPA and BTNL3 were significantly and positively associated with HDL levels.…”

Section: Discussionmentioning

confidence: 99%

Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia

Liu

Guo

Wang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundPreeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Whether genetic factors play a role in abnormal lipid metabolism during the incidence of preeclampsia has not been well investigated.MethodsPreeclampsia patients (n = 110) and healthy age- and gravidity-matched pregnant women (n = 110) were enrolled in this study. Peripheral blood specimens were used for genomic analysis (n = 10/group) or laboratory validation (n = 100/group). We retrospectively obtained the baseline clinical characteristics of 68 preeclampsia patients and 107 controls in early pregnancy (12–14 gestational weeks). Correlation analyses between differential genes and baseline lipid profiles were performed to identify candidate genes. In vitro and in vivo gain-of-function models were constructed with lentivirus and adeno-associated virus systems, respectively, to investigate the role of candidate genes in regulating lipid metabolism and the development of preeclampsia.ResultsWe observed that preeclampsia patients exhibited significantly elevated plasma TC (P = 0.037) and TG (P < 0.001) levels and increased body mass index (P = 0.006) before the disease onset. Within the region of 27 differential copy number variations, six genes potentially connected with lipid metabolism were identified. The aberrant copies of APOBEC3A, APOBEC3A_B, BTNL3, and LMF1 between preeclampsia patients and controls were verified by quantitative polymerase chain reaction. Especially, APOBEC3A showed a significant positive correlation with TC (P < 0.001) and LDL (P = 0.048) in early pregnancy. Then, our in vitro data revealed that overexpression of APOBEC3A disrupted lipid metabolism in HepG2 cells and affected both cholesterol and fatty acid metabolisms. Finally, in vivo study in a hepatic-specific overexpressed APOBEC3A mouse model revealed abnormal parameters related to lipid metabolism. Pregnant mice of the same model at the end of pregnancy showed changes related to preeclampsia-like symptoms, such as increases in sFlt-1 levels and sFlt-1/PLGF ratios in the placenta and decreases in fetal weight.ConclusionOur findings established a new link between genetics and lipid metabolism in the pathogenesis of preeclampsia and could contribute to a better understanding of the molecular mechanisms of preeclampsia.

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“…The use of HCRs as a continuous variable is an advantage compared with IUGR measures based on the categorization of visual observations of body shape. Although studies have been able to determine IUGR through visual judgment and the categorization of BW [ 3 , 6 , 7 , 20 ], our approach might be valuable in determining subclinical IUGR. Remarkably, the linear mixed model estimates presented in our study allow us to estimate BW, colostrum intake, and ADG, considering other important factors that occur during the first week of life that are also associated with IUGR [ 28 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…The number of piglets weaned per litter is an important indicator of the profitability of swine operations, and it is the most important indicator of sow productivity [ 1 , 2 , 3 ]. Nonetheless, current evidence suggests that a larger litter size also increases the proportion of piglets with lower birth weight and colostrum intake, as well as impaired suckling behavior, gut adaptation, and survival [ 1 , 4 , 5 , 6 ], which are associated with piglets’ exposure to intrauterine growth-retardation (IUGR). This disorder has become a major problem for the swine industry, affecting approximately 5% to 10% of pregnancies [ 1 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…This results in less myofiber hyperplasia, fatter carcasses, and lower meat quality compared with heavier piglets within the litter [ 1 ]. In addition, piglets affected by IUGR show lower immune organ weights in the thymus, spleen, and mesenteric lymph nodes, as well as a reduced number of goblet cells and lymphocytes and decreased gene expression and levels of cytokines [ 6 , 14 ]. Thus, the assessment of piglets with impaired intrauterine growth at an early age may have a pivotal role in the success of vaccinations against important clinical conditions, such as diseases associated with porcine circovirus type 2 (PCV-2), and in the success of strategies to improve the overall immune status, from birth to finishing.…”

Section: Introductionmentioning

confidence: 99%

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Association between Head-to-Chest Circumference Ratio and Intrauterine Growth-Retardation Related Outcomes during Preweaning and Postweaning

Manríquez

Poudevigne

Roche

et al. 2022

Animals

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The objective of this study is to evaluate the association between the head-to-chest circumference ratio (HCR) and birth weight (BW), colostrum intake, and average daily weight gain (ADG) at preweaning and postweaning periods. Additionally, associations between HCR and PCV-2 serum antibody titers and the PCV-2 seroconversion ratio (SCR) were assessed. Head and chest circumferences were measured at birth, and HCR was calculated from 110 piglets born from 8 pregnant sows randomly selected from maternity pens. Linear mixed models were used to test whether changes in HCR were associated with fluctuations of BW, colostrum intake, and ADG. In addition, HCR least-square means were compared between piglets classified as lower or greater BW, colostrum intake, and ADG. Finally, receiving operating characteristic curve analyses were performed to estimate HCR thresholds for discriminating between lower and greater performance piglets during preweaning and postweaning periods. Increments in HCR were associated with lower BW, colostrum intake, and ADG. An HCR threshold of 0.82 maximized sensibility and specificity for the classification of lower and greater performance piglets regarding BW, colostrum intake, and ADG during the periods of 0 to 7 and 0 to 69 days of life. When piglets were categorized into HCR ≤ 0.82 and HCR > 0.82 groups, piglets with HCR ≤ 0.82 had lower (log10) PCV-2 serum antibody titers at 26 days of life compared with piglets with HCR > 0.82 (3.30 ± 0.05 vs. 3.47 ± 0.05 g/dL). On the other hand, piglets that showed low SCR between 26 and 69 days of life had greater HCRs compared with piglets with high SCRs (0.83 ± 0.008 vs. 0.8 ± 0.008). The use of HCRs allowed us to identify piglets with lower performance and impaired immune response against PCV-2. The HCR indicator could be used as a selection criterion for preventive management for piglets showing delayed performance potentially associated with IUGR.

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Transcriptome Differences Suggest Novel Mechanisms for Intrauterine Growth Restriction Mediated Dysfunction in Small Intestine of Neonatal Piglets

Cited by 13 publications

References 76 publications

Cohousing-mediated microbiota transfer from milk bioactive components-dosed mice ameliorate colitis by remodeling colonic mucus barrier and lamina propria macrophages

Cohousing-mediated microbiota transfer from milk bioactive components-dosed mice ameliorate colitis by remodeling colonic mucus barrier and lamina propria macrophages

Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia

Association between Head-to-Chest Circumference Ratio and Intrauterine Growth-Retardation Related Outcomes during Preweaning and Postweaning

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