Background:The interaction between nutrition and immunity plays a vital role in nutrient digestion,absorption,and metabolism during poultry production.Recent studies showed that the gut microbiota contributes to the d...Background:The interaction between nutrition and immunity plays a vital role in nutrient digestion,absorption,and metabolism during poultry production.Recent studies showed that the gut microbiota contributes to the development of intestinal mucosal immunity.However,the mechanisms by which gut microbes regulate this process remain unclear.Methods:We compared the intestinal mucosal immunity and gut microbiota of Arbor Acre broilers AA(lower mucosal immunity)and Chinese native Wuliang Mountain Black-bone chickens(WLMB)(higher mucosal immunity)using 16S rDNA sequencing,transcriptomic analysis,and immunoglobulin A(IgA)antibody repertoire sequencing.We then combined 16S rDNA sequencing with transcriptomics to identify the key microbes and found that they were positively correlated with IgA production.Next,we transplanted candidate microbes into 1-day-old broiler to explore their role in intestinal mucosal immunity.Finally,we verified the function of candidate microbial metabolites in regulating the immune function of macrophages and the intestinal-epithelial cells(IECs)using in vitro experiments.Results:WLMB performs stronger mucosal immunity than AA,including higher IgA levels,more diverse IgA antibody repertoire,and higher bacterial affinity.Bacteroides was identified as the key microbes related to the intestinal IgA response.Bacteroides transplantation could increase IgA concentration in the duodenal contents by enhancing the expression of IgA,polymeric immunoglobin receptor(PIgR),B cell-activating factor of the TNF family(BAFF),and activation-induced cytidine deaminase(AID)in the duodenum.Additionally,Bacteroides-derived isovaleric acid promoted M2 macrophage polarization of macrophage via mTOR/PPAR-γ/STAT3 signaling pathways and regulated the immunologic function of IECs to produce cytokines,including interleukin(IL)-10,IL-4,BAFF,and transforming growth factor-beta(TGF-β),thus promoting IgA production in B cells by facilitating AID expression.Conclusion:Our study revealed that Bacteroides modulate the intestinal IgA response and maintain gut health in broilers.Bacteroides may be a promising alternative as an immunomodulatory microbial agent for developing nextgeneration probiotics for broiler production.展开更多
BACKGROUND Isovaleric acidemia(IVA)is a rare autosomal recessive inherited organic acidemia caused by a genetic deficiency of isovaleryl-CoA dehydrogenase(IVD).Its morbidity is low,but mortality is high.There is no ef...BACKGROUND Isovaleric acidemia(IVA)is a rare autosomal recessive inherited organic acidemia caused by a genetic deficiency of isovaleryl-CoA dehydrogenase(IVD).Its morbidity is low,but mortality is high.There is no effective cure for this disease.Early identification of IVA using clinical features can significantly slow disease progression and reduce mortality.Here we report a Chinese neonate with two mutations of IVD and share valuable information on this disease.CASE SUMMARY A 12-day-old male neonate with“poor response for 1 d and repeated convulsions accompanied by high muscle tension for 6 h”was hospitalized.The patient was the first child of nonconsanguineous ethnic Chinese parents.He was delivered by cesarean section due to breech position at 39+1 wk of gestation with a birth weight of 3.27 kg.Initially,he suffered from dyspnea and rhinobyon,and at 10 d after birth the patient suddenly developed poor feeding,low response,lethargy and seizures.Organic acid analysis of blood and urine by tandem mass spectrometry and gas chromatography mass spectrometry showed extremely high concentrations of isovaleryl glycine.The patient had an acute episode of IVA causing severe metabolic stress and eventually died.CONCLUSION A new case of an IVA patient carrying c.1193G>A(p.Arg398Gln)and c.1208A>G(p.Try403Cys)mutations is reported in China.展开更多
Background Isoacids are the product of branched-chain amino acid fermentation and are naturally producedin the hindgut by microbial fermentation. In ruminants, supplementation of isoacids as a feed additive improvesfi...Background Isoacids are the product of branched-chain amino acid fermentation and are naturally producedin the hindgut by microbial fermentation. In ruminants, supplementation of isoacids as a feed additive improvesfiber utilization, with a positive impact on animal productivity. However, information on how isoacids impact nutrientdigestibility in swine is limited. The objective of this experiment was to determine the optimal inclusion levelof an isoacid blend product based on apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD)of nutrients and fermentation products in the ileal digesta and feces of growing pigs fed a corn-soybean meal diet.Methods Twelve ileal cannulated pigs (20.9 ± 0.6 kg) were used in a 5-period crossover design with 6 diets and 2replicate pigs in each period. Dietary treatments consisted of increasing levels (0%, 0.5%, 0.75%, 1%, 1.25%, and 1.5%)of an isoacid blend (isobutyrate, isovalerate, and 2-methyl butyrate, 1:1:1) added to a corn-soybean meal basal diet.Each experimental period consisted of 14 d: 10 d for acclimatization to the diets, 2 d for fecal collection, and 2 dfor digesta collection.Results Isoacids supplementation quadratically improved the AID of hemicellulose (P < 0.05) and tended to improvethe AID of crude fiber (P < 0.1). The AID of most indispensable amino acids (except Met + Cys, Trp, and Val) as wellas the ATTD of crude protein, gross energy, neutral detergent fiber, and hemicellulose improved or tended to improvelinear or quadratically (P < 0.05 or P < 0.1). In addition, the ATTD values of Arg, His, Ile, Leu, Met + Cys, Phe, Thr, and Valincreased quadratically (P < 0.05). Collectively, 1% of isoacids inclusion resulted in the greatest response. Furthermore,isoacids supplementation tended to increase (P = 0.071, quadratically) the concentration of ammonia and decreased(P < 0.05) the concentrations of acetic acid and total volatile fatty acids with a tendency to decrease (P = 0.064) isovalericacid in the ileal digesta. In fecal samples, the proportion of acetic acid decreased (P < 0.05) quadratically, whereas the proportionsof propionic, valeric, and caproic acids tended to increase linearly and/or quadratically (P < 0.1).Conclusions Isoacids supplementation at 1% in swine diets can improve nutrient digestibility, particularly aminoacids and fiber at the ileal level and ATTD of crude protein, gross energy, and hemicellulose.展开更多
基金supported by the National Natural Science Foundation of China (31925037)to XHY。
文摘Background:The interaction between nutrition and immunity plays a vital role in nutrient digestion,absorption,and metabolism during poultry production.Recent studies showed that the gut microbiota contributes to the development of intestinal mucosal immunity.However,the mechanisms by which gut microbes regulate this process remain unclear.Methods:We compared the intestinal mucosal immunity and gut microbiota of Arbor Acre broilers AA(lower mucosal immunity)and Chinese native Wuliang Mountain Black-bone chickens(WLMB)(higher mucosal immunity)using 16S rDNA sequencing,transcriptomic analysis,and immunoglobulin A(IgA)antibody repertoire sequencing.We then combined 16S rDNA sequencing with transcriptomics to identify the key microbes and found that they were positively correlated with IgA production.Next,we transplanted candidate microbes into 1-day-old broiler to explore their role in intestinal mucosal immunity.Finally,we verified the function of candidate microbial metabolites in regulating the immune function of macrophages and the intestinal-epithelial cells(IECs)using in vitro experiments.Results:WLMB performs stronger mucosal immunity than AA,including higher IgA levels,more diverse IgA antibody repertoire,and higher bacterial affinity.Bacteroides was identified as the key microbes related to the intestinal IgA response.Bacteroides transplantation could increase IgA concentration in the duodenal contents by enhancing the expression of IgA,polymeric immunoglobin receptor(PIgR),B cell-activating factor of the TNF family(BAFF),and activation-induced cytidine deaminase(AID)in the duodenum.Additionally,Bacteroides-derived isovaleric acid promoted M2 macrophage polarization of macrophage via mTOR/PPAR-γ/STAT3 signaling pathways and regulated the immunologic function of IECs to produce cytokines,including interleukin(IL)-10,IL-4,BAFF,and transforming growth factor-beta(TGF-β),thus promoting IgA production in B cells by facilitating AID expression.Conclusion:Our study revealed that Bacteroides modulate the intestinal IgA response and maintain gut health in broilers.Bacteroides may be a promising alternative as an immunomodulatory microbial agent for developing nextgeneration probiotics for broiler production.
文摘BACKGROUND Isovaleric acidemia(IVA)is a rare autosomal recessive inherited organic acidemia caused by a genetic deficiency of isovaleryl-CoA dehydrogenase(IVD).Its morbidity is low,but mortality is high.There is no effective cure for this disease.Early identification of IVA using clinical features can significantly slow disease progression and reduce mortality.Here we report a Chinese neonate with two mutations of IVD and share valuable information on this disease.CASE SUMMARY A 12-day-old male neonate with“poor response for 1 d and repeated convulsions accompanied by high muscle tension for 6 h”was hospitalized.The patient was the first child of nonconsanguineous ethnic Chinese parents.He was delivered by cesarean section due to breech position at 39+1 wk of gestation with a birth weight of 3.27 kg.Initially,he suffered from dyspnea and rhinobyon,and at 10 d after birth the patient suddenly developed poor feeding,low response,lethargy and seizures.Organic acid analysis of blood and urine by tandem mass spectrometry and gas chromatography mass spectrometry showed extremely high concentrations of isovaleryl glycine.The patient had an acute episode of IVA causing severe metabolic stress and eventually died.CONCLUSION A new case of an IVA patient carrying c.1193G>A(p.Arg398Gln)and c.1208A>G(p.Try403Cys)mutations is reported in China.
基金financially supported by Zinpro Corporation(grant number:SA2300029,2022–2025).
文摘Background Isoacids are the product of branched-chain amino acid fermentation and are naturally producedin the hindgut by microbial fermentation. In ruminants, supplementation of isoacids as a feed additive improvesfiber utilization, with a positive impact on animal productivity. However, information on how isoacids impact nutrientdigestibility in swine is limited. The objective of this experiment was to determine the optimal inclusion levelof an isoacid blend product based on apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD)of nutrients and fermentation products in the ileal digesta and feces of growing pigs fed a corn-soybean meal diet.Methods Twelve ileal cannulated pigs (20.9 ± 0.6 kg) were used in a 5-period crossover design with 6 diets and 2replicate pigs in each period. Dietary treatments consisted of increasing levels (0%, 0.5%, 0.75%, 1%, 1.25%, and 1.5%)of an isoacid blend (isobutyrate, isovalerate, and 2-methyl butyrate, 1:1:1) added to a corn-soybean meal basal diet.Each experimental period consisted of 14 d: 10 d for acclimatization to the diets, 2 d for fecal collection, and 2 dfor digesta collection.Results Isoacids supplementation quadratically improved the AID of hemicellulose (P < 0.05) and tended to improvethe AID of crude fiber (P < 0.1). The AID of most indispensable amino acids (except Met + Cys, Trp, and Val) as wellas the ATTD of crude protein, gross energy, neutral detergent fiber, and hemicellulose improved or tended to improvelinear or quadratically (P < 0.05 or P < 0.1). In addition, the ATTD values of Arg, His, Ile, Leu, Met + Cys, Phe, Thr, and Valincreased quadratically (P < 0.05). Collectively, 1% of isoacids inclusion resulted in the greatest response. Furthermore,isoacids supplementation tended to increase (P = 0.071, quadratically) the concentration of ammonia and decreased(P < 0.05) the concentrations of acetic acid and total volatile fatty acids with a tendency to decrease (P = 0.064) isovalericacid in the ileal digesta. In fecal samples, the proportion of acetic acid decreased (P < 0.05) quadratically, whereas the proportionsof propionic, valeric, and caproic acids tended to increase linearly and/or quadratically (P < 0.1).Conclusions Isoacids supplementation at 1% in swine diets can improve nutrient digestibility, particularly aminoacids and fiber at the ileal level and ATTD of crude protein, gross energy, and hemicellulose.