The amino acid sensor MetRS is required for methionine-induced milk protein synthesis in a domestic pigeon model.

This study was conducted to investigate whether methionyl-tRNA synthetase (MetRS) is a mediator of Met-induced crop milk protein synthesis via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signalling pathway in breeding pigeons. In Experiment 1, a total of 216 pairs of breeding pigeons were divided into 3 groups (control, Met-deficient, and Met-rescue groups). In Experiments 2 and 3, forty pairs of breeding pigeons from each experiment were allocated into 4 groups. The 2nd experiment included a control group and 3 MetRS inhibitor (REP8839) groups. The 3rd experiment included a Met-deficient group, Met-sufficient group, REP8839 + Met-deficient group, and REP8839 + Met-sufficient group. Experiment 1 showed that Met supplementation increased crop development, crop milk protein synthesis, the protein expression of MetRS and JAK2/STAT5 signalling pathway, and improved squab growth. Experiment 2 showed that crop development, crop milk protein synthesis, and the protein expression of MetRS and the JAK2/STAT5 signalling pathway were decreased, and squab growth was inhibited by the injection of 1.0 mg/kg BW REP8839, which was the selected dose for the 3rd experiment. These results showed that Met supplementation increased crop development, crop milk protein synthesis, and the expression of MetRS and JAK2/STAT5 signalling pathway and rescued squab growth after the injection of REP8839. Moreover, the Co-IP results showed that there was an interaction between MetRS and JAK2. Taken together, these findings indicate that MetRS mediates Met-induced crop milk protein synthesis via the JAK2/STAT5 signalling pathway, resulting in improved squab growth in breeding pigeons.

Lowering mortality risk in CR-HvKP infection in intestinal immunohistological and microbiota restoration.

Gut damage during carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-HvKP) infection is associated with a death risk. Understanding the mechanisms by which CR-HvKP causes intestinal damage and gut microbiota alteration, and the impact on immunity, is crucial for developing therapeutic strategies. This study investigated if gastrointestinal tract damage and disruption of gut microbiota induced by CR-HvKP infection undermined host immunity and facilitated multi-organ invasion of CR-HvKP; whether the therapeutic value of the rifampicin (RIF) and zidovudine (ZDV) combination was attributed to their ability to repair damages and restore host immunity was determined. A sepsis model was utilized to assess the intestinal pathological changes. Metagenomic analysis was performed to characterize the alteration of gut microbiota. The effects of the RIF and ZDV on suppressing inflammatory responses and improving immune functions and gut microbiota were evaluated by immunopathological and transcriptomic analyses. Rapid colonic damage occurred upon activation of the inflammation signaling pathways during lethal infections. Gut inflammation compromised host innate immunity and led to a significant decrease in probiotics abundance, including Bifidobacterium and Lactobacillus. Treatment with combination drugs significantly attenuated the inflammatory response, up-regulated immune cell differentiation signaling pathways, and promoted the abundance of Bifidobacterium (33.40 %). Consistently, supplementation of Bifidobacterium alone delayed the death in sepsis model. Gut inflammation and disrupted microbiota are key disease features of CR-HvKP infection but can be reversed by the RIF and ZDV drug combination. The finding that these drugs can restore host immunity through multiple mechanisms is novel and deserves further investigation of their clinical application potential.

Maternal or post-weaning dietary fructo-oligosaccharide supplementation reduces stillbirth rate of sows and diarrhea of weaned piglets.

Fructo-oligosaccharides (FOS) are well-known prebiotics that have the potential to improve sow reproductive performance and increase piglet growth. However, previous studies were observed in sole FOS-supplemented diets of sows or weaned piglets and did not consider the sow-to-piglet transfer effect on the performance and diarrhea rate of weaned piglets. This study explores the effects of dietary FOS supplementation on the reproductive performance of sows, and the effects of FOS supplementation at different stages on the growth performance and diarrhea rate of weaned piglets. A split-plot experimental design was used with sow diet effect in the whole plot and differing piglet diet effect in the subplot. Fifty-two multiparous sows (223.24 ± 14.77 kg) were randomly divided into 2 groups (0 or 0.2% FOS). The experiment lasted from day 85 of gestation to day 21 of lactation. Reproductive performance, glucose tolerance, placental angiogenesis, and intestinal flora of sows were assessed. At weaning, 192 weaned piglets were grouped in 2 × 2 factorial designs, with the main effects of FOS supplemental level of sow diet (0 and 0.2%), and FOS supplemental level of weaned piglet diet (0 and 0.2%), respectively. The growth performance and diarrhea rate of the weaned piglets were analyzed during a 28-d experiment. Maternal dietary supplementation of FOS was shown to reduce the stillbirth and invalid piglet rates (P < 0.05), improve the insulin sensitivity (P < 0.05) and fecal scores (P < 0.05) of sows, increase the abundance of Akkermansia muciniphila (P = 0.016), decrease the abundance of Escherichia coli (P = 0.035), and increase the isovalerate content in feces (P = 0.086). Meanwhile, the placental angiogenesis marker CD31 expression was increased in sows fed FOS diet (P < 0.05). Moreover, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets (P < 0.05) and increased the content of short-chain fatty acids in feces (P < 0.05). Furthermore, only post-weaning dietary FOS supplementation could improve nutrient digestibility of weaned piglets (P < 0.05). Collectively, FOS supplementation in sows can reduce stillbirth rate, perinatal constipation, and insulin resistance, as well as improve placental vascularization barrier. Additionally, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets, but only FOS supplementation in piglets alone at weaning stage could improve their nutrient digestibility.

Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.

The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukaemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with cachectic hallmarks. Biological samples and clinical data were collected from 30 antibiotic-free AML patients at diagnosis and matched volunteers (1:1) in a multicenter cross-sectional prospective study. The composition and functional potential of the faecal microbiota were analyzed using shotgun metagenomics. Faecal, blood, and urine metabolomics analyses were performed. AML patients displayed muscle weakness, anorexia, signs of altered gut function, and glycaemic disorders. The composition of the faecal microbiota differed between patients with AML and control subjects, with an increase in oral bacteria. Alterations in bacterial functions and faecal metabolome support an altered redox status in the gut microbiota, which may contribute to the altered redox status observed in patients with AML. Eubacterium eligens, reduced 3-fold in AML patients, was strongly correlated with muscle strength and citrulline, a marker of enterocyte mass and function. Blautia and Parabacteroides, increased in patients with AML, were correlated with anorexia. Several bacterial taxa and metabolites (e.g. Blautia, Prevotella, phenylacetate, and hippurate) previously associated with glycaemic disorders were altered. Our work revealed important perturbations in the gut microbiome of AML patients at diagnosis, which are associated with muscle strength, altered redox status, and anorexia. These findings pave the way for future mechanistic work to explore the function and therapeutic potential of the bacteria identified in this study.

Clinical use of tigecycline may contribute to the widespread dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae strains.

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses grave threats to human health. These strains increased dramatically in clinical settings in China in the past few years but not in other parts of the world. Four isogenic K. pneumoniae strains, including classical K. pneumoniae, carbapenem-resistant K. pneumoniae (CRKP), hypervirulent K. pneumoniae (hvKP) and CR-hvKP, were created and subjected to phenotypic characterization, competition assays, mouse sepsis model and rat colonization tests to investigate the mechanisms underlying the widespread nature of CR-hvKP in China. Acquisition of virulence plasmid led to reduced fitness and abolishment of colonization in the gastrointestinal tract, which may explain why hvKP is not clinically prevalent after its emergence for a long time. However, tigecycline treatment facilitated the colonization of hvKP and CR-hvKP and reduced the population of Lactobacillus spp. in animal gut microbiome. Feeding with Lactobacillus spp. could significantly reduce the colonization of hvKP and CR-hvKP in the animal gastrointestinal tract. Our data implied that the clinical use of tigecycline to treat carbapenem-resistant K. pneumoniae infections facilitated the high spread of CR-hvKP in clinical settings in China and demonstrated that Lactobacillus spp. was a potential candidate for anticolonization strategy against CR-hvKP.

Konjac flour-mediated gut microbiota alleviates insulin resistance and improves placental angiogenesis of obese sows.

Our previous study revealed that dietary konjac flour (KF) could remodel gut microbiota and improve reproductive performance of sows, but its underlying mechanisms remain unclear. This experiment aimed to investigate how dietary KF improves reproductive performance of obese sows. Here, 60 sows were assigned into three groups according to their backfat thickness: normal backfat sows fed with control diet (CON-N), high backfat sows fed with control diet (CON-H) and high backfat sows fed with KF inclusion diet (KF-H). The characteristics of sows and piglets were recorded. Next, fecal microbiota transplantation (FMT) was performed on female mice, followed by recording the characteristics of female mice. The results showed that compared with CON-H group, KF-H group showed downtrend in stillbirth rate (P = 0.07), an increase in placental efficiency (P < 0.01) and average piglet weight (P < 0.01); coupled with a decrease in the values of homeostasis model assessment-insulin resistance (P < 0.01); as well as an increase in placental vascular density and protein expression of angiogenesis markers (P < 0.01). As expected, sows fed KF diets had improved abundance and diversity of gut microbiota. More importantly, compared with CON-H(FMT) group, KF-H(FMT) group showed improvement in reproductive performance and insulin sensitivity (P < 0.05), as well as an increase in placental labyrinth zone and protein expression of angiogenesis markers (P < 0.05). Furthermore, we found a content increase (P < 0.05) of SCFAs in both KF-H group sow and KF-H (FMT) group mice. Overall, KF supplementation could alleviate insulin resistance, promote placental angiogenesis, and ultimately improve the reproductive performance of sows via gut microbiota remodeling.

Lachnospiraceae-derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus.

Inflammation-associated insulin resistance is a key trigger of gestational diabetes mellitus (GDM), but the underlying mechanisms and effective interventions remain unclear. Here, we report the association of placental inflammation (tumor necrosis factor-α) and abnormal maternal glucose metabolism in patients with GDM, and a high fermentable dietary fiber (HFDF; konjac) could reduce GDM development through gut flora-short-chain fatty acid-placental inflammation axis in GDM mouse model. Mechanistically, HFDF increases abundances of Lachnospiraceae and butyrate, reduces placental-derived inflammation by enhancing gut barrier and inhibiting the transfer of bacterial-derived lipopolysaccharide, and ultimately resists high-fat diet-induced insulin resistance. Lachnospiraceae and butyrate have similar anti-GDM and anti-placental inflammation effects, and they can ameliorate placental function and pregnancy outcome effects probably by dampening placental immune dysfunction. These findings demonstrate the involvement of important placental inflammation-related mechanisms in the progression of GDM and the great potential of HFDFs to reduce susceptibility to GDM through gut-flora-placenta axis.

Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss.

BACKGROUND & AIMS: Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks. METHODS: 10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited. Samples and data were collected before any therapeutic intervention (T0), at the end of the SIC (T1) and at discharge (T4). Gut microbiota composition and function, markers of inflammation, metabolism, gut barrier function and cachexia, as well as faecal, blood and urine metabolomes were assessed. RESULTS: AML patients demonstrated decreased appetite, weight loss and muscle wasting during hospitalization, with an incidence of cachexia of 50%. AML intensive treatment transiently impaired the gut barrier function and led to a long-lasting change of gut microbiota composition characterized by an important loss of diversity. Lactobacillaceae and Campylobacter concisus were increased at T1 while Enterococcus faecium and Staphylococcus were increased at T4. Metabolomics analyses revealed a reduction in urinary hippurate and faecal bacterial amino acid metabolites (bAAm) (2-methylbutyrate, isovalerate, phenylacetate). Integration using DIABLO revealed a deep interconnection between all the datasets. Importantly, we identified bacteria which disappearance was associated with impaired gut barrier function (Odoribacter splanchnicus) and body weight loss (Gemmiger formicilis), suggesting these bacteria as actionable targets. CONCLUSION: AML intensive therapy transiently impairs the gut barrier function while inducing enduring alterations in the composition and metabolic activity of the gut microbiota that associate with body weight loss. TRIAL REGISTRATION: NCT03881826, https://clinicaltrials.gov/ct2/show/NCT03881826.

Structural variation and introgression from wild populations in East Asian cattle genomes confer adaptation to local environment.

BACKGROUND: Structural variations (SVs) in individual genomes are major determinants of complex traits, including adaptability to environmental variables. The Mongolian and Hainan cattle breeds in East Asia are of taurine and indicine origins that have evolved to adapt to cold and hot environments, respectively. However, few studies have investigated SVs in East Asian cattle genomes and their roles in environmental adaptation, and little is known about adaptively introgressed SVs in East Asian cattle. RESULTS: In this study, we examine the roles of SVs in the climate adaptation of these two cattle lineages by generating highly contiguous chromosome-scale genome assemblies. Comparison of the two assemblies along with 18 Mongolian and Hainan cattle genomes obtained by long-read sequencing data provides a catalog of 123,898 nonredundant SVs. Several SVs detected from long reads are in exons of genes associated with epidermal differentiation, skin barrier, and bovine tuberculosis resistance. Functional investigations show that a 108-bp exonic insertion in SPN may affect the uptake of Mycobacterium tuberculosis by macrophages, which might contribute to the low susceptibility of Hainan cattle to bovine tuberculosis. Genotyping of 373 whole genomes from 39 breeds identifies 2610 SVs that are differentiated along a "north-south" gradient in China and overlap with 862 related genes that are enriched in pathways related to environmental adaptation. We identify 1457 Chinese indicine-stratified SVs that possibly originate from banteng and are frequent in Chinese indicine cattle. CONCLUSIONS: Our findings highlight the unique contribution of SVs in East Asian cattle to environmental adaptation and disease resistance.

Prevalence and genetic basis of tetracycline resistance in Vibrioparahaemolyticus isolates recovered from food products in Shenzhen, China during 2013 to 2021.

Understanding tetracycline resistance in Vibrio parahaemolyticus from food products is crucial for effective control measures against this foodborne pathogen. This study aimed to investigate the prevalence, evolution routes, and mechanism of transmission of tetracycline resistance in Vibrio parahaemolyticus isolates collected from food products in Shenzhen, China. A total of 2342 non-duplicate Vibrio parahaemolyticus were isolated from 3509 food samples during the period 2013-2021. Among these 2342 Vibrio parahaemolyticus strains, 530 (21.37 %) were resistant to tetracycline. These tetracycline-resistant Vibrio parahaemolyticus strains were mainly isolated from shrimp samples, with the highest resistance rate (46.9 %) observed in 2019. Phylogenetic and genomic analyses of 387 isolates carrying the tet genes revealed that five different types of tet genes (tet(34), tet(A), tet(B), tet(M), and tet(E)) were present. The tet(A) gene was the most common (65 % of isolates), while tet(E) and tet(M) genes were only detected in specific years. Although tet(A) is the most commonly detected gene, it only encodes resistance in a low percentage of strains (47/129). On the other hand, the resistance rate is highest in isolates carrying tet(B) (41/55). Interestingly, V. parahaemolyticus carrying the tet genes were not necessarily tetracycline-resistant, and vice versa. A total of six different types of plasmids and two transposable units were found to carry the tet genes. V. parahaemolyticus strains that harbored these plasmids were often resistant to multiple antibiotics, indicating that horizontal transfer of antibiotic resistance genes is common among V. parahaemolyticus strains. Our findings suggest a high prevalence of tetracycline resistance in Vibrio parahaemolyticus strains recovered from food products in Shenzhen, China. These results provide valuable insight into the evolution and transmission of tetracycline resistance in foodborne Vibrio parahaemolyticus isolates and highlight the need for effective control measures to prevent the spread of antibiotic resistance.

l-Malic Acid Facilitates Stem Cell-Driven Intestinal Epithelial Renewal through the Amplification of ß-Catenin Signaling by Targeting Frizzled7 in Chicks.

l-Malic acid (l-MA) contributes to energy metabolism and nutrient digestion, which is an alternative to antibiotics for livestock; however, it is not clear whether l-MA can replace antibiotics to promote intestinal development in chicks. To investigate the effects of l-MA on intestinal stem cells (ISCs) driving epithelial renewal, we employed in vivo chick feeding experiments, chick intestinal organoid (IO) models, and in vitro chick intestinal epithelial cell models. The results showed that the feed conversion rate and diarrhea scores were decreased with improved jejunal morphology and barrier function in the 0.5% l-MA group. l-MA promoted the proliferation and differentiation of ISCs, inhibited the cell apoptosis, increased the IO formation efficiency, surface area, budding efficiency, and number of buds, suggesting that l-MA promoted the expansion of ISCs. Furthermore, l-MA treatment dramatically upregulated the Wnt/ß-catenin signaling pathway in the jejunum. Importantly, Wnt transmembrane receptor Frizzled7 (FZD7) mRNA abundance was increased in response to dietary 0.5% l-MA. In addition, molecular docking analysis using Autodock software and isothermal titration calorimetry revealed that l-MA binds to Lys91 of FZD7 with high affinity, indicating a spontaneous interaction. The chick intestinal epithelial cells treated with 10 µM l-MA significantly increased cell viability, and the Wnt/ß-catenin signaling pathway was activated, but l-MA failed to upregulate the Wnt/ß-catenin signaling when treated with the FZD7-specific inhibitor Fz7-21 in chick intestinal epithelial cells, indicating that FZD7 is indispensable for l-MA activation of the Wnt/ß-catenin signaling. Collectively, l-MA stimulated ß-catenin signaling by targeting transmembrane receptor FZD7, which promoted ISC expansion and inhibited cell apoptosis to accelerate intestinal epithelial renewal in chicks.

Cysteamine and N-Acetyl-cysteine Alleviate Placental Oxidative Stress and Barrier Function Damage Induced by Deoxynivalenol.

Sows are highly sensitive to deoxynivalenol (DON) and susceptible to reproductive toxicity caused by oxidative stress, but the potential mechanisms and effective interventions remain unclear. Here, we investigated the role of two antioxidants (cysteamine and N-acetyl-cysteine) in regulating the reproductive performance, redox status, and placental barrier function of sows and their potential mechanisms under DON exposure. Maternal dietary supply of antioxidants from day 85 of gestation to parturition reduced the incidence of stillbirths and low-birth-weight piglets under DON exposure. Moreover, the alleviation of DON-induced reproductive toxicity by dietary antioxidants was associated with the alleviation of placental oxidative stress, the enhancement of the placental barrier, and the vascular function of sows. Furthermore, in vivo and in vitro vascularized placental barrier modeling further demonstrated that antioxidants could reverse both DON transport across the placenta and DON-induced increase of placental barrier permeability. The molecular mechanism of antioxidant resistance to DON toxicity may be related to the signal transducer and activator of the transcription-3-occludin/zonula occludens-1 signaling pathway. Collectively, these results demonstrate the potential of antioxidants to protect the mother from DON-induced reproductive toxicity by alleviating placental oxidative stress and enhancing the placental barrier.

A phylogenomic analysis of Limosilactobacillus reuteri reveals ancient and stable evolutionary relationships with rodents and birds and zoonotic transmission to humans.

BACKGROUND: Gut microbes play crucial roles in the development and health of their animal hosts. However, the evolutionary relationships of gut microbes with vertebrate hosts, and the consequences that arise for the ecology and lifestyle of the microbes are still insufficiently understood. Specifically, the mechanisms by which strain-level diversity evolved, the degree by which lineages remain stably associated with hosts, and how their evolutionary history influences their ecological performance remain a critical gap in our understanding of vertebrate-microbe symbiosis. RESULTS: This study presents the characterization of an extended collection of strains of Limosilactobacillus reuteri and closely related species from a wide variety of hosts by phylogenomic and comparative genomic analyses combined with colonization experiments in mice to gain insight into the long-term evolutionary relationship of a bacterial symbiont with vertebrates. The phylogenetic analysis of L. reuteri revealed early-branching lineages that primarily consist of isolates from rodents (four lineages) and birds (one lineage), while lineages dominated by strains from herbivores, humans, pigs, and primates arose more recently and were less host specific. Strains from rodent lineages, despite their phylogenetic divergence, showed tight clustering in gene-content-based analyses. These L. reuteri strains but not those ones from non-rodent lineages efficiently colonize the forestomach epithelium of germ-free mice. The findings support a long-term evolutionary relationships of L. reuteri lineages with rodents and a stable host switch to birds. Associations of L. reuteri with other host species are likely more dynamic and transient. Interestingly, human isolates of L. reuteri cluster phylogenetically closely with strains from domesticated animals, such as chickens and herbivores, suggesting zoonotic transmissions. CONCLUSIONS: Overall, this study demonstrates that the evolutionary relationship of a vertebrate gut symbiont can be stable in particular hosts over time scales that allow major adaptations and specialization, but also emphasizes the diversity of symbiont lifestyles even within a single bacterial species. For L. reuteri, symbiont lifestyles ranged from autochthonous, likely based on vertical transmission and stably aligned to rodents and birds over evolutionary time, to allochthonous possibly reliant on zoonotic transmission in humans. Such information contributes to our ability to use these microbes in microbial-based therapeutics.

Pathological Features and Genomic Characterization of an Actinobacillus equuli subsp. equuli Bearing Unique Virulence-Associated Genes from an Adult Horse with Pleuropneumonia.

Actinobacillus equuli subsp. equuli is the etiological agent of sleepy foal disease, an acute form of fatal septicemia in newborn foals. A. equuli is commonly found in the mucous membranes of healthy horses' respiratory and alimentary tracts and rarely causes disease in adult horses. In this study, we report a case of a 22-year-old American Paint gelding presenting clinical signs associated with an atypical pattern of pleuropneumonia subjected to necropsy. The gross and histopathological examinations revealed a unilateral fibrinosuppurative and hemorrhagic pleuropneumonia with an infrequent parenchymal distribution and heavy isolation of A. equuli. The whole genome sequence analysis indicated that the isolate shared 95.9% homology with the only other complete genome of A. equuli subsp. equuli available in GenBank. Seven virulence-associated genes specific to the isolate were identified and categorized as iron acquisition proteins, lipopolysaccharides (LPS), and capsule polysaccharides. Moreover, four genes (glf, wbaP, glycosyltransferase family 2 protein, and apxIB) shared higher amino acid similarity with the invasive Actinobacillus spp. than the reference A. equuli subsp. equuli genome. Availability of the whole genome sequence will allow a better characterization of virulence determinants of A. equuli subsp. equuli, which remain largely elusive.

Metagenomic analysis provides bases on individualized shift of colon microbiome affected by delaying colostrum feeding in neonatal calves.

This study investigated the effect of colostrum feeding time on the colon digesta microbiome of 2-day-old dairy calves using whole-genome-based metagenome sequencing, aiming to understand the dynamic changes of the colon microbiome when the colostrum feeding is delayed. In total, 24 male Holstein calves were grouped to different pasteurized colostrum feeding time treatments randomly: TRT0h (45 min after birth, n = 7); TRT6h (6 h after birth, n = 8); and TRT12h (12 h after birth, n = 9). Bacteria, archaea, eukaryotes, and viruses were identified in the colon microbiome, with bacteria (99.20%) being the most predominant domain. Streptococcus, Clostridium, Lactobacillus, Ruminococcus, and Enterococcus were the top five abundant bacteria genera. For colon microbiome functions, 114 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, with nutrients metabolism-related functions "carbohydrate metabolism," "amino acid metabolism," "metabolism of cofactors and vitamins," "metabolism of terpenoids and polyketides," and "metabolism of other amino acids" being the top five secondary level of KEGG hierarchy functions. When colon microbiomes were compared, they were not affected by delaying first colostrum feeding at both taxonomic and functional levels. However, distinct clusters of colon microbiome profiles were shown based on PERMANOVA analysis despite of different colostrum feeding treatment, suggesting the individualized responses. Moreover, the relative abundance of microbial taxa, microbial functions, and differentially expressed genes was compared between the two distinct clusters, and different relationships were observed among host differentially expressed genes, differential levels of microbial taxa, and microbial functions between the two clusters. Our results suggest that the host may play an important role in shaping the colon microbiome of neonatal dairy calves in response to the early life feeding management. Whether the observed colon microbiome shifts affect gut health and function in the long term requires further research.

The Effects of Breed and Residual Feed Intake Divergence on the Abundance and Active Population of Rumen Microbiota in Beef Cattle.

To assess the effects of residual feed intake (RFI) and breed on rumen microbiota, the abundance (DNA) and active population (RNA) of the total bacteria, archaea, protozoa, and fungi in the rumen of 96 beef steers from three different breeds (Angus (AN), Charolais (CH), and Kinsella Composite (KC)), and divergent RFIs (High vs Low), were estimated by measuring their respective maker gene copies using qRT-PCR. All experimental animals were kept under the same feedlot condition and fed with the same high-energy finishing diet. Rumen content samples were collected at slaughter and used for the extraction of genetic material (DNA and RNA) and further analysis. There was a significant difference (p < 0.01) between the marker gene copies detected for abundance and active populations for all four microbial groups. AN steers had a higher abundance of bacteria (p < 0.05) and a lower abundance of eukaryotes (protozoa and fungi, p < 0.05) compared to KC steers, while the abundance of protozoa (p < 0.05) in the AN cattle and fungi (p < 0.05) in the KC cattle were lower and higher, respectively, than those in the CH steers. Meanwhile, the active populations of bacteria, archaea, and protozoa in the KC steers were significantly lower than those in the AN and CH animals (p < 0.01). This work demonstrates that cattle breed can affect rumen microbiota at both the abundance and activity level. The revealed highly active protozoal populations indicate their important role in rumen microbial fermentation under a feedlot diet, which warrants further study.

Expressions of resistome is linked to the key functions and stability of active rumen microbiome.

BACKGROUND: The resistome describes the array of antibiotic resistant genes (ARGs) present within a microbial community. Recent research has documented the resistome in the rumen of ruminants and revealed that the type and abundance of ARGs could be affected by diet and/or antibiotic treatment. However, most of these studies only assessed ARGs using metagenomics, and expression of the resistome and its biological function within the microbiome remains largely unexplored. RESULTS: We characterized the pools of ARGs (resistome) and their activities in the rumen of 48 beef cattle belonging to three breeds (Angus, Charolais, Kinsella composite hybrid), using shotgun metagenomics and metatranscriptomics. Sixty (including 20 plasmid-associated) ARGs were expressed which accounted for about 30% of the total number of ARGs (187) identified in metagenomic datasets, with tetW and mefA exhibiting the highest level of expression. In addition, the bacterial hosts of 17 expressed ARGs were identified. The active resistome was less diverse in Kinsella composite hybrid than Angus, however, expression of ARGs did not differ among breeds. Although not associated with feed efficiency, the total abundance of expressed ARGs was positively correlated with metabolic pathways and 'attenuation values' (a measurement of stability) of the active rumen microbiome, suggesting that ARGs expression influences the stability and functionality of the rumen microbiome. Moreover, Ruminococcus spp., Prevotella ruminicola, Muribaculaceae spp. and Collinsella aerofaciens were all identified as hosts of expressed ARGs, possibly promoting the dominance of these carbohydrate degraders within the rumen microbiome. CONCLUSIONS: Findings from this study provide new insight into the active rumen resistome in vivo, which may inform strategies to limit the spread of ubiquitously found ARGs from the rumen to the broader environment without negatively impacting the key functional outcomes of the rumen microbiome.

Elucidating the role of the gut microbiota in the physiological effects of dietary fiber.

BACKGROUND: Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25-35 kg/m2) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX; n = 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC; n = 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamine N-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers. RESULTS: AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC. CONCLUSION: This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract.