Bacteroides-derived isovaleric acid enhances mucosal immunity by facilitating intestinal IgA response in broilers

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.

Lactobacillus frumenti mediates energy production via fatty acid β-oxidation in the liver of early-weaned piglets

Background:Early-weaning of piglets is often accompanied by severe disorders,especially diarrhea.The gut microbiota and its metabolites play a critical role in the maintenance of the physiologic and metabolic homeostasis of the host.Our previous studies have demonstrated that oral administration of Lactobacillus frumenti improves epithelial barrier functions and confers diarrhea resistance in early-weaned piglets.However,the metabolic response to L.frumenti administration remains unclear.Then,we conducted simultaneous serum and hepatic metabolomic analyses in early-weaned piglets administered by L.frumenti or phosphatebuffered saline(PBS).Results:A total of 1006-day-old crossbred piglets(Landrace×Yorkshire)were randomly divided into two groups and piglets received PBS(sterile,2 m L)or L.frumenti(suspension in PBS,10~8 CFU/m L,2 m L)by oral administration once per day from 6 to 20 days of age.Piglets were weaned at 21 days of age.Serum and liver samples for metabolomic analyses were collected at 26 days of age.Principal components analysis(PCA)showed that L.frumenti altered metabolism in serum and liver.Numerous correlations(P<0.05)were identified among the serum and liver metabolites that were affected by L.frumenti.Concentrations of guanosine monophosphate(GMP),inosine monophosphate(IMP),and uric acid were higher in serum of L.frumenti administration piglets.Pathway analysis indicated that L.frumenti regulated fatty acid and amino acid metabolism in serum and liver.Concentrations of fatty acidβ-oxidation related metabolites in serum(such as3-hydroxybutyrylcarnitine,C4-OH)and liver(such as acetylcarnitine)were increased after L.frumenti administration.Conclusions:Our findings suggest that L.frumenti regulates lipid metabolism and amino acid metabolism in the liver of early-weaned piglets,where it promotes fatty acidβ-oxidation and energy production.High serum concentrations of nucleotide intermediates,which may be an alternative strategy to reduce the incidence of diarrhea in early-weaned piglets,were further detected.These findings broaden our understanding of the relationships between the gut microbiota and nutrient metabolism in the early-weaned piglets.

Effects of Aeriscardovia aeriphila on growth performance,antioxidant functions,immune responses,and gut microbiota in broiler chickens

Aeriscardovia aeriphila,also known as Bifidobacterium aerophilum,was first isolated from the caecal contents of pigs and the faeces of cotton-top tamarin.Bifidobacterium species play important roles in preventing intestinal infections,decreasing cholesterol levels,and stimulating the immune system.In this study,we isolated a strain of bacteria from the duodenal contents of broiler chickens,which was identified as A.aeriphila,and then evaluated the effects of A.aeriphila on growth performance,antioxidant functions,immune functions,and gut microbiota in commercial broiler chickens.Chickens were orally gavaged with A.aeriphila(1×109 CFU/mL)for 21 d.The results showed that A.aeriphila treatment significantly increased the average daily gain and reduced the feed conversion ratio(P<0.001).The levels of serum growth hormone(GH)and insulin-like growth factor 1(IGF-1)were significantly increased following A.aeriphila treatment(P<0.05).Blood urea nitrogen and aspartate aminotransferase levels were decreased,whereas glucose and creatinine levels increased as a result of A.aeriphila treatment.Furthermore,the levels of serum antioxidant enzymes,including catalase(P<0.01),superoxide dismutase(P<0.001),and glutathione peroxidase(P<0.05),and total antioxidant capacity(P<0.05)were enhanced following A.aeriphila treatment.A.aeriphila treatment significantly increased the levels of serum immunoglobulin A(IgA)(P<0.05),IgG(P<0.01),IgM(P<0.05),interleukin-1(IL-1)(P<0.05),IL-4(P<0.05),and IL-10(P<0.05).The broiler chickens in the A.aeriphila group had higher secretory IgA(SIgA)levels in the duodenum(P<0.01),jejunum(P<0.001),and cecum(P<0.001)than those in the control group.The messenger RNA(mRNA)relative expression levels of IL-10(P<0.05)and IL-4(P<0.001)in the intestinal mucosa of chickens were increased,while nuclear factor-κB(NF-κB)(P<0.001)expression was decreased in the A.aeriphila group compared to the control group.Phylum-level analysis revealed Firmicutes as the main phylum,followed by Bacteroidetes,in both groups.The data also found that Phascolarctobacterium and Barnesiella were increased in A.aeriphila-treated group.In conclusion,oral administration of A.aeriphila could improve the growth performance,serum antioxidant capacity,immune modulation,and gut health of broilers.Our findings may provide important information for the application of A.aeriphila in poultry production.

Multi-omics analysis reveals gut microbiota-induced intramuscular fatdeposition via regulating expression of lipogenesis-associated genes

The gut microbiome has great effects on the digestion, absorption, and metabolism of lipids. However,the microbiota composition that can alter the fat deposition and the meat quality of pigs remains unclear.Here, we used Laiwu (LW) pigs (a native Chinese breed with higher intramuscular fat) compared withcommercial crossbreed Duroc×(Landrace×Yorkshire) (DLY) pigs to investigate the effects of microbiotaon meat quality, especially in intramuscular fat content. A total of 32 DLY piglets were randomly allottedto 4 groups and transplanted with fecal microbiota from healthy LW pigs. The results indicated that thehigh dose of fecal microbiota transplantation (HFMT) selectively enhanced fat deposition in longissimusdorsi (P < 0.05) but decreased backfat thickness (P < 0.05) compared with control group. HFMT significantlyaltered meat color and increased feed conversation ratio (P < 0.05). Furthermore, the multi-omicsanalysis revealed that Bacteroides uniformis, Sphaerochaeta globosa, Hydrogenoanaerobacterium saccharovorans,and Pyramidobacter piscolens are the core species which can regulate lipid deposition. A total of140 male SPF C57BL/6j mice were randomly allotted into 7 groups and administrated with these 4 microbesalone or consortium to validate the relationships between microbiota and lipid deposition.Inoculating the bacterial consortium into mice increased intramuscular fat content (P < 0.05) comparedwith control mice. Increased expressions of lipogenesis-associated genes including cluster of differentiation36 (Cd36), diacylglycerol O-acyltransferase 2 (Dgat2), and fatty acid synthase (FASN) wereobserved in skeletal muscle in the mice with mixed bacteria compared with control mice. Together, ourresults suggest that the gut microbiota may play an important role in regulating the lipid deposition in the muscle of pigs and mice.

Successful resolution of hemophagocytic lymphohistiocytosis during the chemotherapy course of acute myelocytic leukemia with ruxolitinib

To the Editor:Hemophagocytic lymphohistiocytosis(HLH)is a severe or even fatal inflammatory condition.Malignant HLH(M-HLH)is one of the most common types of secondary HLH(sHLH),especially in adults.HLH can occur either as the initial manifestation of malignant disease(here referred to as“malignancy-triggered HLH”)or in the setting of iatrogenic immuno-suppression from chemotherapy(“HLH during chemotherapy”or Ch-HLH).