Host Gut Microbiota Research Articles

Pristimerin Alleviates DSS-Induced Colitis in Mice by Modulating Intestinal Barrier Function, Gut Microbiota Balance and Host Metabolism

Pristimerin Alleviates DSS-Induced Colitis in Mice by Modulating Intestinal Barrier Function, Gut Microbiota Balance and Host Metabolism

Pathobiont and symbiont contribute to microbiota homeostasis through Malpighian tubules-gut countercurrent flow in Bactrocera dorsalis

Abstract Host-gut microbiota interactions are more complex than good or bad. Both gut symbiotic bacteria and pathobionts can provide essential functions to their host in one scenario and yet be detrimental to host health in another. So, these gut-dwelling bacteria must be tightly controlled to avoid harmful effects on the host. However, how pathobionts and other symbiotic bacteria coordinate to establish a host immune defense system remains unclear. Here, using a Tephritidae fruit fly Bactrocera dorsalis, we report that both pathobionts and other gut symbiotic bacteria release tyramine, which is recognized by the host insects. These tyramines induce the formation of insect-conserved Malpighian tubules-gut countercurrent flow upon bacterial infection, which requires tyramine receptors and aquaporins. At the same time, pathobionts but not gut symbiotic bacteria induce the generation of reactive oxygen species, which are preserved by the countercurrent flow, promoting bacteria elimination through increasing gut peristalsis. More importantly, our results show that the Malpighian tubules-gut countercurrent flow maintains proper microbiota composition. Our work suggests a model where pathobiont-induced reactive oxygen species are preserved by Malpighian tubules-gut countercurrent flow involving both pathobionts and symbiotic bacteria. Furthermore, our work provides a Malpighian tubules-gut interaction that ensures efficient maintenance of the gut microbiota.

Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively.Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability.Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels.Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.

Unraveling the Gut Microbiota: Implications for Precision Nutrition and Personalized Medicine

Recent studies have shown a growing interest in the complex relationship between the human gut microbiota, metabolism, and overall health. This review aims to explore the gut microbiota–host association, focusing on its implications for precision nutrition and personalized medicine. The objective is to highlight how gut microbiota modulate metabolic and immune functions, contributing to disease susceptibility and wellbeing. The review synthesizes recent research findings, analyzing key studies on the influence of gut microbiota on lipid and carbohydrate metabolism, intestinal health, neurobehavioral regulation, and endocrine signaling. Data were drawn from both experimental and clinical trials examining microbiota–host interactions relevant to precision nutrition. Our findings highlight the essential role of gut microbiota-derived metabolites in regulating host metabolism, including lipid and glucose pathways. These metabolites have been found to influence immune responses and gut barrier integrity. Additionally, the microbiota impacts broader physiological processes, including neuroendocrine regulation, which could be crucial for dietary interventions. Therefore, understanding the molecular mechanisms of dietary–microbiota–host interactions is pivotal for advancing personalized nutrition strategies. Tailored dietary recommendations based on individual gut microbiota compositions hold promise for improving health outcomes, potentially revolutionizing future healthcare approaches across diverse populations.

Comprehensive genomic analysis and evaluation of in vivo and in vitro safety of Heyndrickxia coagulans BC99

This study aimed to evaluate the safety profile and beneficial effects of Heyndrickxia coagulans strain BC99 (BC99) for potential use in functional foods and pharmaceuticals. We began with whole genome sequencing of BC99, followed by a comprehensive safety assessment comprising genome analysis, hemolysis, cytotoxicity, antibiotic susceptibility tests, and cell adhesion and tolerance studies, along with acute and subacute oral toxicity studies in animal models. BC99 was isolated from a well-characterized collection originating from the feces of a healthy infant. Our results indicated no hemolytic activity on Columbia blood agar plates and broad antibiotic sensitivity, including to gentamicin, ampicillin, chloramphenicol, ciprofloxacin, and others. Cytotoxicity testing confirmed no adverse effects on HT-29 cells and significant adhesive properties to intestinal epithelial cells. Tolerance tests demonstrated over 90% viability of BC99 under simulated gastrointestinal conditions. In vivo studies in mice and rats confirmed the absence of adverse effects following oral administration. Collectively, these findings support BC99’s robust tolerance to gastrointestinal environments, strong adhesion capabilities, and a broad spectrum of antibiotic resistance, underlining its potential as a safe and effective agent for gut microbiota modulation and host health enhancement.

Metabolic interactions of host-gut microbiota: New possibilities for the precise diagnosis and therapeutic discovery of gastrointestinal cancer in the future-a review.

Gastrointestinal (GI) cancer continues to pose a significant global health challenge. Recent advances in our understanding of the complex relationship between the host and gut microbiota have shed light on the critical role of metabolic interactions in the pathogenesis and progression of GI cancer. In this study, we examined how microbiota interact with the host to influence signalling pathways that impact the formation of GI tumours. Additionally, we investigated the potential therapeutic approach of manipulating GI microbiota for use in clinical settings. Revealing the complex molecular exchanges between the host and gut microbiota facilitates a deeper understanding of the underlying mechanisms that drive cancer development. Metabolic interactions hold promise for the identification of microbial signatures or metabolic pathways associated with specific stages of cancer. Hence, this study provides potential strategies for the diagnosis, treatment and management of GI cancers to improve patient outcomes.

Taeniasis impacts human gut microbiome composition and function.

Human taeniasis, caused by Taenia tapeworms, is a global parasitic disease with significant implications for public health and food safety. These tapeworms can grow to considerable sizes and potentially impact the microecology of the host gut. Despite their importance, the effects of Taenia infection on host gut microbiota haven't been thoroughly investigated. In this study, we conducted a cross-sectional analysis of the gut microbiome in patients infected with Taenia asiatica (n = 87) compared to healthy controls (n = 79) in the Dali cohort, China. We also performed a longitudinal assessment of microbial changes following deworming in a subset of patients (n = 24). Our findings reveal a significant shift in gut microbial composition, characterized by increased alpha-diversity and an enrichment of Prevotella-driven enterotypes in infected patients compared to healthy controls. The stability of these microbial features post-deworming varied widely among individuals and was lower in those with lower initial alpha diversity and Prevotella-enterotype before deworming. We observed a significant depletion of Bifidobacterium species in infected individuals, regardless of enterotypes, and these prebiotics did not recover post-deworming. Metabolic network analysis and in vitro experiments suggest that the reduction of Bifidobacterium was linked to metabolic competition for ecological niches or nutrients, particularly stachyose, from other microbes rather than the parasitism itself. Furthermore, our machine learning analysis demonstrated that taxa associated with Bifidobacterium in stachyose metabolism could robustly predict infection but could not predict deworming. This study highlights the substantial impact of taeniasis on the human gut microbiome and overall gut health.

Oral co-administration of Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 improves host defense against influenza A virus infection.

Influenza is an important zoonotic disease that persistently threatens global public health. While it is widely acknowledged that probiotics can modulate the host response to protect the host against infectious disease, the prophylactic efficacy on respiratory viral infection and the detailed mechanism remains elusive. Lactobacillus, the most commonly used probiotic widely applied in food production, has garnered significant attention. In our study utilizing both C57BL/6 and BALB/c mouse models, we explored the protective effect against two strains of influenza virus, A/Mink/China/01/2014(H9N2) and A/California/04/2009(H1N1), through the administration of Lactiplantibacillus plantarum strain 16 (L. plantarum 16) and Lacticaseibacillus rhamnosus strain P118 (L. rhamnosus P118), aiming to identify robust probiotic strains with antiviral properties. Our findings indicate that administering L. plantarum 16 or L. rhamnosus P118 alone does not provide sufficient protection against influenza. However, the co-administration of L. plantarum 16 and L. rhamnosus P118 dramatically reduces viral titers in the respiratory tract and lung, thereby markedly alleviating the clinical symptoms, improving prognosis, and reducing mortality. The mechanisms underlying this effect involve the modulation of host gut microbiota and metabolism through the co-administration of L. plantarum 16 and L. rhamnosus P118, resulting in enrichment of Firmicutes and enhancement of phenylalanine-related metabolism, ultimately leading to an augmentation of the antiviral immune response. Notably, we identified that the circulating metabolic molecule 2-Hydroxycinnamic acid plays a significant role in combating influenza. Our data suggest the potential utility of L. plantarum 16 and L. rhamnosus P118 two-bacterium or 2-Hydroxycinnamic acid in preventing influenza.IMPORTANCEVaccination represents the most optimal strategy to control influenza. Nevertheless, influenza viruses constantly evolve due to antigenic drift and shift, leading to the need for regular updates on influenza vaccines. Additionally, vaccination failure poses significant challenges to influenza prevention. Therefore, it is essential and beneficial to identify novel or universal antiviral measures to protect against influenza. While cumulative data suggest that probiotics offer protection against infectious diseases, the specific mechanisms, such as the effective metabolites or components, remain largely unknown. Our research discovered the capacity of combinational two-bacterium Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 to fight against influenza infection in a mouse model. The protection may occur through modulating the host's gut microbiota and metabolism, further influencing the host's antiviral immune response. Notably, we have identified a novel metabolic molecule, 2-Hydroxycinnamic acid, capable of enhancing antiviral response and restricting viral replication in vivo.

Trace antibiotic exposure affects murine gut microbiota and metabolism

Gut microbiota is important for host metabolism regulation. Antibiotic exposure disturbs this regulation by affecting the microbiome. Trace levels of antibiotics in water have been widely reported and the impact on gut microbiota remains understudied. We provide evidence of trace antibiotic exposure affecting the host's gut microbiota using a mouse model exposed to trace amounts of azithromycin (AZI) or ciprofloxacin (CIP) in drinking water. AZI exposure in males changed the distribution of gram-positive (Firmicutes and Bacteroidetes) and gram-negative (Proteobacteria, Fusobacteria, and Verrucomicrobia) bacteria at an early age. Both AZI and CIP resulted in abnormal microbiota maturation. Additionally, the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, in females is affected. Serum hormone and metabolome levels shifted after trace antibiotic exposure. AZI and CIP exposure broadly disrupted original host-microbe interaction relationships between the gut microbiota and SCFAs or serum metabolites. In this study, we demonstrated that trace antibiotic exposure was associated with extensive gut microbiota and metabolism perturbation in mice and that the potential health risks in susceptible populations should be considered.

Bioactive Compounds and Their Chondroprotective Effects for Osteoarthritis Amelioration: A Focus on Nanotherapeutic Strategies, Epigenetic Modifications, and Gut Microbiota

In degenerative joint disease like osteoarthritis (OA), bioactive compounds like resveratrol, epigallocatechin gallate, curcumin, and other polyphenols often target various signalling pathways, including NFκB, TGFβ, and Wnt/β-catenin by executing epigenetic-modifying activities. Epigenetic modulation can target genes of disease pathophysiology via histone modification, promoter DNA methylation, and non-coding RNA expression, some of which are directly involved in OA but have been less explored. OA patients often seek options that can improve the quality of their life in addition to existing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Although bioactive and natural compounds exhibit therapeutic potential against OA, several disadvantages loom, like insolubility and poor bioavailability. Nanoformulated bioactive compounds promise a better way to alleviate OA since they also control systemic events, including metabolic, immunological, and inflammatory responses, by modulating host gut microbiota that can regulate OA pathogenesis. Recent data suggest gut dysbiosis in OA. However, limited evidence is available on the role of bioactive compounds as epigenetic and gut modulators in ameliorating OA. Moreover, it is not known whether the effects of polyphenolic bioactive compounds on gut microbial response are mediated by epigenetic modulatory activities in OA. This narrative review highlights the nanotherapeutic strategies utilizing bioactive compounds, reporting their effects on chondrocyte growth, metabolism, and epigenetic modifications in osteoarthritis amelioration.

Parameter Estimation of Host Genomic and Gut Microbiota Contribution to Growth and Feed Efficiency Traits in Meat Rabbits.

Rabbits can efficiently utilize plant fibers that are indigestible to humans, and hence may contribute to the alleviation of feed-food competition. Therefore, it is economically and ecologically important to genetically improve the growth performance and feed efficiency of meat rabbits. In this study, we combined pedigree, genomic, and gut microbiota data to estimate genetic and microbial parameters for nine growth and feed efficiency traits of 739 New Zealand White rabbits, including body weight (BW) at 35 (BW35), 70 (BW70), and 84 (BW84) days of age, and average daily gain (ADG), feed conversion ratio (FCR), and residual feed intake (RFI) within two age intervals of 35-70 days (ADG70, FCR70, and RFI70) and 35-84 days (ADG84, FCR84, and RFI84). Based on single-step genomic best linear unbiased prediction, three BW traits and two ADG traits had the high estimates (±standard error, SE) of heritability, ranging from 0.44 ± 0.13 of BW35 to 0.66 ± 0.08 of BW70. Moderate heritabilities were observed for RFI70 (0.22 ± 0.07) and RFI84 (0.29 ± 0.07), whereas the estimates did not significantly deviate from zero for the two FCR traits. There was moderate positive genetic correlation (±SE) between BW70 and ADG70 (0.579 ± 0.086), but BW70 did not correlate with RFI70. Based on microbial best linear unbiased prediction, the estimates of microbiability did not significantly deviate from zero for any trait. Based on the combined use of genomic and gut microbiota data, the parameters obtained in this study could help us to implement efficient breeding schemes in meat rabbits.

The modulation of intestinal commensal bacteria possibly contributes to the growth and immunity promotion in Epinephelus akaara after feeding the antimicrobial peptide Scy-hepc.

Our previous study revealed that feeding the antimicrobial peptide (AMP) product Scy-hepc significantly enhances the growth of mariculture fish through the activation of the GH-Jak2-STAT5-IGF1 axis. However, the contribution of gut microbiota to this growth enhancement remains unclear. This study aimed to elucidate the potential mechanism involved in intestinal absorption and modulation of gut microbiota in Epinephelus akaara following Scy-hepc feeding. The results showed that a 35day regimen of Scy-hpec markedly promoted the growth of E. akaara compared to groups supplemented with either florfenicol, B. subtilis, or a vector. The growth enhancement is likely attributed to alterations in microbiota colonization in the foregut and midgut, characterized by an increasing abundance of potential probiotics (Rhizobiaceae and Lysobacter) and a decreased abundance of opportunistic pathogens (Psychrobacter and Brevundimonas) as determined by 16S rRNA analysis. Additionally, similar to the effect of florfenicol feeding, Scy-hepc significantly improved host survival rate by over 20% in response to a lethal dose challenge with Edwardsiella tarda. Further investigations demonstrated that Scy-hepc is absorbed by the fish foregut (20-40min) and midgut (20-30min) as confirmed by Western blot, ELISA, and Immunofluorescence. The absorption of Scy-hepc affected the swimming, swarming and surfing motility of Vibrio harveyi and Bacillus thuringiensis isolated from E. akaara's gut. Moreover, Scy-hepc induced the downregulation of 40 assembly genes and the upregulation expression of 5, with the most significant divergence in gene expression between opportunistic pathogens and probiotics concentrated in their motility genes (PomA/B, MotA/B). In summary, this study shows that feeding AMP Scy-hepc can promote growth and bolster immunity in E. akaara. These beneficial effects are likely due to the absorption of Scy-hepc in the fish's foregut and midgut, which modulates the colonization and motility of commensal bacteria, leading to favorable changes in the composition of the foregut and midgut microbiota. Therefore, a profound understanding of the mechanisms by which antimicrobial peptides affect host gut microbiota will contribute to a comprehensive assessment of their advantages and potential application prospects as substitutes for antibiotics in fish health and improving aquaculture practices.

Aged garlic oligosaccharides modulate host metabolism and gut microbiota to alleviate high-fat and high-cholesterol diet-induced atherosclerosis in ApoE−/− mice

Atherosclerosis (AS) is a cardiovascular disease caused by excessive accumulation of lipids in arterial walls. In this study, we developed an AS model in ApoE−/− mice using a high-fat, high-cholesterol diet and investigated the anti-AS mechanism of aged garlic oligosaccharides (AGOs) by focusing on the gut microbiota. Results revealed that AGOs exhibited significant anti-AS effects, reduced trimethylamine N-oxide levels from 349.9 to 189.2 ng/mL, and reduced aortic lipid deposition from 31.7 % to 9.5 %. AGOs significantly increased the levels of short-chain fatty acids in feces, in which acetic, propionic, and butyric acids were increased from 1.580, 0.364, and 0.469 mg/g to 2.233, 0.774, and 0.881 mg/g, respectively. An analysis of the gut microbiota indicated that AGOs restored alpha and beta diversity, decreased the Firmicutes/Bacteroidetes ratio, and promoted the dominance of the genus Akkermansia. A metagenomic analysis revealed that AGOs alleviated AS through the ABC transporter pathway and the lipopolysaccharide biosynthesis pathway.

Dissecting causal relationships between gut microbiome, immune cells, and brain injury: A Mendelian randomization study.

Increasing literature has affirmed that changes in the gut microbiome (GM) composition were linked to distinct brain injury (BI) through the gut-brain axis, but it is uncertain if such links reflect causality. Further, the immune cell changes mediating the impact of GM on BI are not completely understood. We made use of the summary statistics of 211 GM (MiBioGen consortium), 731 immune cells, and 2 different BIs (FinnGen consortium), namely traumatic BI (TBI) and focal BI (FBI), from the extensive genome-wide association studies to date. We executed bidirectional Mendelian randomization (MR) analyses to ascertain the causal relationships between the GM and BI, and 2-step MR to validate possible mediating immune cells. Additionally, thorough sensitivity analyses verified the heterogeneity, robustness, as well as horizontal pleiotropy of the results. Based on the results of inverse-variance weighted (IVW) and sensitivity analyses, in MR analyses, 5 specific GM taxa and 6 specific GM taxa were causally associated with FBI and TBI, respectively; 27 immunophenotypes and 39 immunophenotypes were causally associated with FBI and TBI, respectively. Remarkably, Anaerofilum, LachnospiraceaeNC2004group, RuminococcaceaeUCG004, CCR2 on myeloid dendritic cell (DC), CD123 on CD62L+ plasmacytoid DC, and CD123 on plasmacytoid DC were causally associated with TBI and FBI (all P < .040). However, our reverse MR did not indicate any influence of TBI and FBI on the specific GM. In mediation analysis, we found that the associations between Escherichia.Shigella and FBI were mediated by CD123 on CD62L + plasmacytoid DC in addition to CD123 on plasmacytoid DC, each accounting for 4.21% and 4.21%; the association between FamilyXIIIAD3011group and TBI was mediated by CCR2 on myeloid DC, with mediated proportions of 5.07%. No remarkable horizontal pleiotropy or heterogeneity of instrumental variables was detected. Our comprehensive MR analysis first provides insight into potential causal links between several specific GM taxa with FBI/TBI. Additionally, CD123 on plasmacytoid DC in conjunction with CCR2 on myeloid DC may function in gut microbiota-host crosstalk in FBI and TBI, correspondingly. Further studies are critical to unravel the underlying mechanisms of the links between GM and BI.

From raw milk cheese to the gut: investigating the colonization strategies of Bifidobacterium mongoliense.

The microbial ecology of raw milk cheeses is determined by bacteria originating from milk and milk-producing animals. Recently, it has been shown that members of the Bifidobacterium mongoliense species may become transmitted along the Parmigiano Reggiano cheese production chain and ultimately may colonize the consumer intestine. However, there is a lack of knowledge regarding the molecular mechanisms that mediate the interaction between B. mongoliense and the human gut. Based on 128 raw milk cheeses collected from different Italian regions, we isolated and characterized 10 B. mongoliense strains. Comparative genomics allowed us to unveil the presence of enzymes required for the degradation of sialylated host-glycans in B. mongoliense, corroborating the appreciable growth on de Man-Rogosa-Sharpe (MRS) medium supplemented with 3'-sialyllactose (3'-SL) or 6'-sialyllactose (6'-SL). The B. mongoliense BMONG18 was chosen, due to its superior ability to utilize 3'-SL and mucin as representative strain, to investigate its behavior when co-inoculated with other bifidobacterial species. Conversely, members of other bifidobacterial species did not appear to benefit from the presence of BMONG18, highlighting a competitive scenario for nutrient acquisition. Transcriptomic data of BMONG18 reveal no significant differences in gene expression when cultivated in a gut simulating medium (GSM), regardless of whether cheese was included or not. Furthermore, BMONG18 was shown to exhibit high adhesion capabilities to HT29-MTX human cells, in line with its colonization ability of a human host.IMPORTANCEFermented foods are nourishments produced through controlled microbial growth that play an essential role in worldwide human nutrition. Research interest in fermented foods has increased since the 80s, driven by growing awareness of their potential health benefits beyond mere nutritional content. Bifidobacterium mongoliense, previously identified throughout the production process of Parmigiano Reggiano cheese, was found to be capable of establishing itself in the intestines of its consumers. Our study underscores molecular mechanisms through which this bifidobacterial species, derived from food, interacts with the host and other gut microbiota members.

Uncovering new Firmicutes species in vertebrate hosts through metagenome-assembled genomes with potential for sporulation.

Metagenome-assembled genomes (MAGs) have contributed to identifying non-culturable microorganisms and understanding their ecological functions. MAGs offer an advantage in investigating sporulation-associated genes, especially given the difficulty of isolating many species residing in the gut microbiota of multiple hosts. Bacterial sporulation is a key survival mechanism with implications for pathogenicity and biotechnology. Here, we investigate MAGs from vertebrate hosts, emphasizing taxonomic identification and identifying sporulation-associated genes in potential novel species within the Firmicutes phylum. We identified potential new species in the classes Clostridia (Borkfalkiaceae, Lachnospiraceae, Monoglobaceae, and Oscillospiraceae families) and Bacilli (Bacillaceae and Erysipelotrichaceae families) through phylogenetic and functional pathway analyses, highlighting their sporulation potential. Our study covers 146 MAGs, 124 of them without refined taxonomic assignments at the family level. We found that Clostridia and Bacilli have unique sporulation gene profiles in the refined family MAGs for cattle, swine, poultry, and human hosts. The presence of genes related to Spo0A regulon, engulfment, and spore cortex in MAGs underscores fundamental mechanisms in sporulation processes in currently uncharacterized species with sporulation potential from metagenomic dark matter. Furthermore, genomic analyses predict sporulation potential based on gene presence, genome size, and metabolic pathways involved in spore formation. We emphasize MAGs covering families not yet characterized through the phylogenetic analysis, and with extensive potential for spore-forming bacteria within Clostridia, Bacilli, UBA4882, and UBA994 classes. These findings contribute to exploring spore-forming bacteria, which provides evidence for novel species diversity in multiple hosts, their adaptive strategies, and potential applications in biotechnology and host health.IMPORTANCESpores are essential for bacterial survival in harsh environments, facilitating their persistence and adaptation. Exploring sporulation-associated genes in metagenome-assembled genomes (MAGs) from different hosts contributes to clinical and biotechnological domains. Our study investigated the extent of genes associated with bacterial sporulation in MAGs from poultry, swine, cattle, and humans, revealing these genes in uncultivated bacteria. We identified potential novel Firmicutes species with sporulation capabilities through phylogenetic and functional analyses. Notably, MAGs belonging to Clostridia, Bacilli, and unknown classes, namely UBA4882 and UBA994, remained uncharacterized at the family level, which raises the hypothesis that sporulation would also be present in these genomes. These findings contribute to our understanding of microbial adaptation and have implications for microbial ecology, underlining the importance of sporulation in Firmicutes across different hosts. Further studies into novel species and their sporulation capability can contribute to bacterial maintenance mechanisms in various organisms and their applications in biotechnology studies.

Unveiling the dynamic processes of dietary advanced glycation end-products (dAGEs) in absorption, accumulation, and gut microbiota metabolism.

This study delves into the dynamics of dietary advanced glycation end-products (dAGEs) on host health and gut microbiota. Using 13C-labeled carboxymethyllysine (CML) bound casein, we identify bound AGEs as the primary entry route, in contrast to free AGEs dominating urinary excretion. Specifically, our results show that the kidneys accumulate 1.5 times more dAGEs than the liver. A high AGE (HA) diet prompts rapid gut microbiota changes, with an initial stress-induced mutation phase, evidenced by a 20% increase in Bacteroides and Parabacteroides within the first week, followed by stabilization. These bacteria emerge as potential dAGE-utilizing bacteria, influencing the microbiota composition. Concurrent metabolic shifts affect lipid and carbohydrate pathways, with lipid metabolism alterations persisting over time, impacting host metabolic homeostasis. This study illuminates the intricate interplay between dietary AGEs, gut microbiota, and host health, offering insights into the health consequences of short- and long-term HA dietary patterns.

40 The gut microbiota modifies host-parasite interactions

Abstract It is well documented that parasitic infections induce a profound change in the structure and function of host gut microbiota, likely due to infection-associated perturbations in the gut microenvironment. However, the mechanisms remain largely unknown. Here we aim to understand how the gut microbiota is modified by host-parasite relationships or vice versa using an integrated multi-omics analysis in a swine-Ascaris infection model. Female pigs (n = 30; 6 to 8 mo of age) were randomly divided into three groups (n = 10 per group). One group served as normal uninfected controls (NU); the remaining 20 pigs were inoculated per os with ~10,000 infective A. suum eggs; and the infection was allowed to progress for 35 d post-inoculation (dpi). At 21 dpi, one of the infected groups (IP) was treated with a single daily dose of an anthelmintic drug, Panacur, for three consecutive days while the other infected pigs remained untreated (IU). At necropsy, intestine tissue, serum and fecal samples were collected for untargeted metabolome analysis using UPLC-MS/MS and the fecal microbiota was characterized using full-length 16S rRNA gene-based sequencing with DADA2. Fecal and serum metabolites were categorized for their origin using MetOrigin. An integrated multi-omics analysis was performed using DIABLO algorithms and NetCoMi networking tools. Our results showed that A. suum worms were well developed in pigs from the IU group, which harbored a significantly reduced microbiota alpha diversity (Simpson, P &amp;lt; 0.005) compared with NU. The infection altered the abundance of at least 17 bacterial species/strains, including multiple butyrate-producing Clostridium spp., such as C. butyricum. The infection also dysregulated 51 fecal metabolites, including microbiota-derived metabolites such as glutaric acid and p-Cresol sulfate, and succinate of mixed origin. Moreover, the anthelmintic treatment was efficacious and eliminated all worms from the gut. Nevertheless, 11 pathways of both host and microbiota origin were significantly enriched in the gut of pigs from the IP group, including peptidoglycan biosynthesis, histidine metabolism (in both feces and serum), and primary bile acid biosynthesis, suggesting the infection-induced alterations may not be transient. In conclusion, the host microbiota modified swine-Ascaris interactions via three different mechanisms. First, microbiota-derived metabolites directly regulate host gene expression, which in turn affects host physiology and immune responses. Second, plasticity of the gut microbiota allows the exploitation of the niche differentiated upon infection, resulting in blossom of certain strains in the gut of post-treated animals. Lastly, the host microbiota is likely one of the key determinants of parasite gut microbiota, indirectly exerting its effect on parasite physiology and nutrition. Further studies aiming to understand reciprocal yet complex relations between the gut microbiota, the host, and parasites (including parasite gut microbiota) will be conducive to the design of next-generation functional anthelmintics.

Host genetics and gut microbiota synergistically regulate feed utilization in egg-type chickens

BackgroundFeed efficiency is a crucial economic trait in poultry industry. Both host genetics and gut microbiota influence feed efficiency. However, the associations between gut microbiota and host genetics, as well as their combined contributions to feed efficiency in laying hens during the late laying period, remain largely unclear.MethodsIn total, 686 laying hens were used for whole-genome resequencing and liver transcriptome sequencing. 16S rRNA gene sequencing was conducted on gut chyme (duodenum, jejunum, ileum, and cecum) and fecal samples from 705 individuals. Bioinformatic analysis was performed by integrating the genome, transcriptome, and microbiome to screen for key genetic variations, genes, and gut microbiota associated with feed efficiency.ResultsThe heritability of feed conversion ratio (FCR) and residual feed intake (RFI) was determined to be 0.28 and 0.48, respectively. The ileal and fecal microbiota accounted for 15% and 10% of the FCR variance, while the jejunal, cecal, and fecal microbiota accounted for 20%, 11%, and 10% of the RFI variance. Through SMR analysis based on summary data from liver eQTL mapping and GWAS, we further identified four protein-coding genes, SUCLA2, TNFSF13B, SERTM1, and MARVELD3, that influence feed efficiency in laying hens. The SUCLA2 and TNFSF13B genes were significantly associated with SNP 1:25664581 and SNP rs312433097, respectively. SERTM1 showed significant associations with rs730958360 and 1:33542680 and is a potential causal gene associated with the abundance of Corynebacteriaceae in feces. MARVELD3 was significantly associated with the 1:135348198 and was significantly correlated with the abundance of Enterococcus in ileum. Specifically, a lower abundance of Enterococcus in ileum and a higher abundance of Corynebacteriaceae in feces were associated with better feed efficiency.ConclusionsThis study confirms that both host genetics and gut microbiota can drive variations in feed efficiency. A small portion of the gut microbiota often interacts with host genes, collectively enhancing feed efficiency. Therefore, targeting both the gut microbiota and host genetic variation by supporting more efficient taxa and selective breeding could improve feed efficiency in laying hens during the late laying period.

Multi-omics analysis reveals associations between host gene expression, gut microbiota, and metabolites in chickens.

Egg-laying is an important trait in chickens, and it is affected by many factors, such as hormones regulated by the hypothalamic-pituitary axis and precursors synthesized by the liver. Recent studies showed that gut microbiota was associated with egg-laying, however, its underlying mechanism remains unclear. We comprehensively analyzed the host transcriptome, gut microbiota, and metabolome in broiler breeder hens during the pre-laying, peak-laying, and late-laying periods. The transcriptome analysis of the tissues related to the hypothalamic-pituitary-liver (HPL) axis revealed dynamic gene expression during egg-laying periods. Differentially expressed genes (DEGs) (i.e., PENK, NPY, AVP, PRL, RLN3, and FST) from the hypothalamus and pituitary gland were involved in female gonadal development, hormone secretion, response to endogenous stimulus, liver development, and amide metabolism. In liver, DEGs (i.e., FABP3, VTG1, LPL, APOA5, APOV1, and RBP5) were enriched in efferocytosis, sphingolipid metabolism, amide, and peptide biosynthesis. Alpha and beta diversity changed significantly in cecum microbiota during different laying periods. The abundance of Firmicutes was decreased and the abundance of Bacteroidota was increased during the peak-laying period. Functional analysis showed that the biosynthesis of secondary metabolites, amino acids, purine, and steroid hormones was altered during laying. The metabolome analysis from cecal contents showed that amino acid metabolism and steroid hormone biosynthesis changed during laying. Integrated analysis of the cecal microbiota and metabolites showed the genus Megasphaera was involved in amino acid metabolism, which included 3-phenyllatic acid, quinic acid, caffeic acid, and folic acid, and the genus Hungatella participated in steroid hormone biosynthesis through its strong correlation with estradiol. These results explored the dynamic changes in tissues related to the HPL axis and cecal microbiota and provided new insights into the interaction between the host and microbiota during egg-laying in chickens.