Gut Microbial Function Research Articles

Strategic alteration of arabinoxylan feruloylation enables selective shaping of the human gut microbiota

Arabinoxylans (AXs) are promising prebiotic candidates abundant in cereals. While AX feruloylation impacts properties, its effects on long chains mimicking native structures are unclear. This study revealed a dose-dependent impact of long chain AX feruloylation on gut microbial composition and function. In vitro fecal fermentation with varying AX feruloylation showed increased Bacteroidetes and propionate along with decreased Firmicutes and butyrate. Distinct Bacteroides populations were enriched under different feruloylation levels, suggesting specialized adaptation. Community dynamics and co-occurrence networks highlighted intricate taxon-specific responses, underscoring the unique microbial profiles shaped by individual variations. This study lays the foundation for elucidating the metabolic pathways and enzymatic machineries enabling utilization of feruloylated AXs based on the dose-dependent enrichment of specific taxa. This knowledge can inform rational design of customized prebiotics through precision nutrition. This work provides novel insights into tailoring cereal biomass fermentation and microbiome structure-function relationships. It establishes a platform for developing optimized feruloylated prebiotics to deliberately modulate gut ecology and address intestinal dysbiosis.

Maternal gastrointestinal microbiome shapes gut microbial function and resistome of newborns in a cow-to-calf model

BackgroundThe maternal gut microbiome is the direct and important source of early colonization and development of the neonatal gut microbiome. However, differences in unique and shared features between mothers with different physiological phenotypes and their newborns still lack exhaustive investigation. Here, using a cow-to-calf model, a comprehensive investigation was conducted to elucidate the pattern and characterization of microbial transfer from the maternal source to the offspring.ResultsThe microbiota in the rumen and feces of dairy cows were divided into two clusters via enterotype analysis. The cows from the enterotype distinguished by Prevotella in the rumen had better production performance, whereas no difference was observed in the cows classified by feces enterotype. Furthermore, through a pairwise combination of fecal and ruminal enterotypes, we screened a group of dairy cows with excellent phenotypes. The gastrointestinal microbiomes of cows with different phenotypes and their offspring differed significantly. The rumen was a more important microbial source for meconium than feces. Transmission of beneficial bacteria from mother to offspring was observed. Additionally, the meconium inherits advantageous metabolic functions of the rumen. The resistome features of the rumen, feces, and meconium were consistent, and resistome abundance from cows to calves showed an expanding trend. The interaction between antibiotic-resistance genes and mobile genetic elements from the rumen to meconium was the most remarkable. The diversity of core metabolites from cows to calves was stable and not affected by differences in phenotypes. However, the abundance of specific metabolites varied greatly.ConclusionsOur study demonstrates the microbial taxa, metabolic function, and resistome characteristics of maternal and neonatal microbiomes, and reveals the potential vertical transmission of the microbiome from a cow-to-calf model. These findings provide new insights into the transgenerational transmission pattern of the microbiome.2cueHjjtpyRzwmAWUdZ5oAVideo

Structural and functional differences of gut microbiota in Pomacea canaliculata from different geographical locations and habitats.

Gut microbiota is related to host fitness, and influenced by geographical locations and habitats. Pomacea canaliculata is a malignant invasive alien snail that threatens agricultural production and ecosystem functions worldwide. Clarifying the general rules of the gut microbial community structure and function of the snails in different geographical locations and habitats is of great significance for understanding their invasion at different spatial scales. This study used high-throughput sequencing technology to compare and analyze the differences in community structure and function of gut microbiota in P. canaliculata from five geographical locations (Liuzhou, Yulin, Nanning, Wuzhou, and Hezhou) and three different habitats (pond, paddy field, and ditch) in Guangxi Province. The results showed that intestinal microbial alpha diversity of P. canaliculata was higher in Liuzhou, Yulin, lower in Nanning, Wuzhou, Hezhou, and higher in ponds compared with paddy fields and ditches. The dominant phyla of gut microbiota in snails were Firmicutes, Cyanobacteria, Proteobacteria, Fusobacteriota, Bacteroidota, and the dominant genus was Lactococcus. The community structure of gut microbiota in snails varied significantly across different geographical locations and habitats, and the phyla Firmicutes, Cyanobacteria had significantly higher relative abundance in snails collected from Nanning and Yulin, respectively. Moreover, the relative abundance of gut functional microbiota associated with human disease in P. canaliculata was significantly affected by geographical locations and habitats, and with the highest abundance in ponds. However, the relative abundance of functional microbiota related to metabolism, genetic information processing, organizational system, environmental information processing, and cellular processes were only significantly affected by geographical locations. Collectively, geographical locations and habitats had significantly different effects on the community structure and function of gut microbiota in P. canaliculata, and the greater differences were caused by geographical locations rather than by habitats.

Gut microbiota dynamics of adult and sub‐adult sika deer during reintroduction

AbstractPrey populations significantly influence the distribution of top predators. The sika deer (Cervus nippon), a key prey species for the Amur tiger in Northeast China, plays a critical role in the recovery and dispersal of Amur tiger populations. Reintroduction is a pivotal strategy for restoring prey populations, but it presents challenges, especially in terms of adaptation to the natural environment during the natural training process before animals are released. In this study, we sampled six adult and six sub‐adult sika deer and employed high‐throughput sequencing of the 16S ribosomal RNA gene to investigate changes in gut microbial diversity, composition, and function during natural training. The results showed that adult sika deer had higher gut microbiota diversity compared to sub‐adults. However, as natural training progressed, the gut microbial diversity in sub‐adults approached that of adults. Additionally, beneficial, fiber‐digesting bacteria associated with adaptation to the natural environment tended to increase during nature training in both adult and sub‐adult sika deer, while pathogenic bacteria tended to decrease. We also compared the metabolic function of the gut microbiota in adult and sub‐adult sika deer, which showed that the carbohydrate metabolic function of both adults and sub‐adults decreased significantly with natural training, declining more rapidly in sub‐adults. Conversely, the lipid metabolic function in sub‐adults increased significantly with natural training. Overall, a period of nature training is necessary before reintroducing animals to their natural habitats, and sub‐adult sika deer, in particular, exhibit greater adaptability to environmental changes as reflected by their gut microbiota dynamics. These findings offer valuable insights for the reintroduction of sika deer and other ungulates. We recommend incorporating natural training in reintroduction programs and prioritizing sub‐adult animals for reintroduction.

Environmentally acquired gut-associated bacteria are not critical for growth and survival in a solitary bee, Megachile rotundata.

Social bees have been extensively studied for their gut microbial functions, but the significance of the gut microbiota in solitary bees remains less explored. Solitary bee, Megachile rotundata females provision their offspring with pollen from various plant species, harboring a diverse microbial community that colonizes larvae guts. The Apilactobacillus is the most abundant microbe, but evidence concerning the effects of Apilactobacillus and other provision microbes on growth and survival are lacking. We hypothesized that the presence of Apilactobacillus in abundance would enhance larval and prepupal development, weight, and survival, while the absence of intact microbial communities was expected to have a negative impact on bee fitness. We reared larvae on pollen provisions with naturally collected microbial communities (Natural pollen) or devoid of microbial communities (Sterile pollen). We also assessed the impact of introducing Apilactobacillus micheneri by adding it to both types of pollen provisions. Feeding larvae with sterile pollen + A. micheneri led to the highest mortality rate, followed by natural pollen + A. micheneri, and sterile pollen. Larval development was significantly delayed in groups fed with sterile pollen. Interestingly, larval and prepupal weights did not significantly differ across treatments compared to natural pollen-fed larvae. 16S rRNA gene sequencing found a dominance of Sodalis, when A. micheneri was introduced to natural pollen. The presence of Sodalis with abundant A. micheneri suggests potential crosstalk between both, shaping bee nutrition and health. Hence, this study highlights that the reliance on nonhost-specific environmental bacteria may not impact fitness of M. rotundata.IMPORTANCEThis study investigates the impact of environmentally acquired gut microbes of solitary bee fitness with insights into the microbial ecology of bee and their health. While the symbiotic microbiome is well-studied in social bees, the role of environmental acquired microbiota in solitary bees remains unclear. Assessing this relationship in a solitary pollinator, the leaf-cutting bee, Megachile rotundata, we discovered that this bee species does not depend on the diverse environmental bacteria found in pollen for either its larval growth or survival. Surprisingly, high concentrations of the most abundant pollen bacteria, Apilactobacillus micheneri did not consistently benefit bee fitness, but caused larval mortality. Our findings also suggest an interaction between Apilactobacillus and the Sodalis and perhaps their role in bee nutrition. Hence, this study provides significant insights that contribute to understanding the fitness, conservation, and pollination ecology of other solitary bee species in the future.

Gut Microbiome Compositional and Functional Features Associate with Alzheimer's Disease Pathology.

The gut microbiome is a potentially modifiable factor in Alzheimer's disease (AD); however, understanding of its composition and function regarding AD pathology is limited. Shallow-shotgun metagenomic data was used to analyze fecal microbiome from participants enrolled in the Wisconsin Microbiome in Alzheimer's Risk Study, leveraging clinical data and cerebrospinal fluid (CSF) biomarkers. Differential abundance and ordinary least squares regression analyses were performed to find differentially abundant gut microbiome features and their associations with CSF biomarkers of AD and related pathologies. Gut microbiome composition and function differed between people with AD and cognitively unimpaired individuals. The compositional difference was replicated in an independent cohort. Differentially abundant gut microbiome features were associated with CSF biomarkers of AD and related pathologies. These findings enhance our understanding of alterations in gut microbial composition and function in AD, and suggest that gut microbes and their pathways are linked to AD pathology.

Diet and gut microbiome: Impact of each factor and mutual interactions on prevention and treatment of type 1, type 2, and gestational diabetes mellitus

The gut microbiota (GM) plays a key role in health by influencing several physiological functions, including the digestive process, the immune system, vitamin production, and mental health. Dysbiosis in gut microbial composition and function has been linked to systemic inflammatory response and the development of metabolic diseases, including diabetes mellitus (DM). "Leaky gut" resulting from dysbiosis causes endotoxemia, leading to systemic inflammation and insulin resistance, which are pathogenetic agents of type 2 and gestational DM. Moreover, in children, gut dysbiosis has been associated with the immunitary dysregulation with increased risk of autoimmunity and development of type 1 DM. However, dietary changes in the GM and their role in DM are poorly understood. Plant-based diets that are low in fat and high in fiber have been associated with beneficial effects on the GM. Clinical trials of prebiotics and probiotics have shown promising, albeit mixed, results. This narrative review summarizes recent findings on the relationship between the GM, diet, and DM, focusing on the systems in which the microbiota is involved in the pathogenesis of this disease and its potential use as a therapy. In addition, we discuss immune dysfunction associated with gut dysbiosis and its role in type 1, type 2, and gestational DM. Further research is needed to evaluate the GM as a potential therapeutic target for the prevention and treatment of DM.

Mining metagenomic data to gain a new insight into the gut microbial biosynthetic potential in placental mammals.

Mammals host a remarkable diversity and abundance of gut microbes. Biosynthetic gene clusters (BGCs) in microbial genomes encode biologically active chemical products and play an important role in microbe-host interactions. Traditionally, the exploration of gut microbial metabolic functions has relied on the pure culture method. However, given the limited amounts of microbes being cultivated, insights into the metabolism of gut microbes in mammals continued to be very limited. In this study, we adopted a computational pipeline for mining the metagenomic data (named taxonomy-guided identification of biosynthetic gene clusters, TaxiBGC) to identify experimentally verified BGCs in 373 metagenomes across 53 mammalian species in an unbiased manner. We demonstrated that polyketides (PKs) and nonribosomal peptides (NRPs) are representative of mammals, and the products derived from them were associated with cell-cell communication and resistance to inflammation. Large carnivores had the highest number of BGCs, followed by large herbivores and small mammals. We also observed that the large mammals had more common BGCs that aid in the biosynthesis of a variety of natural products. However, small mammals not only had fewer BGCs but were also unique to each species. Our results provide novel insights into the mining of metagenomic data sets to identify active BGCs and their products across mammals.IMPORTANCEThe gut microbes host numerous biosynthetic gene clusters (BGCs) that biosynthesize natural products and impact the host's physiology. Historically, our understanding of BGCs in mammalian gut microbes was largely based on studies on cultured isolates; however, only a small fraction of mammal-associated microbes have been investigated. The biochemical diversity of the mammalian gut microbiota is poorly understood. Metagenomic sequencing contains data from a vast number of organisms and provides information on the total gene content of communities. Unfortunately, the existing BGC prediction tools are designed for individual microbial genomes. Recently, a BGC prediction tool called the taxonomy-guided identification of biosynthetic gene clusters (TaxiBGC) that directly mine the metagenome was developed. To gain new insights into the microbial metabolism, we used TaxiBGC to predict BGCs from 373 metagenomes across 53 mammalian species representing seven orders. Our findings elucidate the functional activities of complex microbial communities in the gut.

The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review.

The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.

Characteristics of stachyose-induced effects on gut microbiota and microbial metabolites in vitro associated with obesity in children.

Childhood obesity presents a serious health concern associated with gut microbiota alterations. Dietary interventions targeting the gut microbiota have emerged as promising strategies for managing obesity in children. This study aimed to elucidate the impact of stachyose (STS) supplementation on the gut microbiota composition and metabolic processes in obese children. Fecal samples were collected from 40 obese children (20 boys and 20 girls) aged between 6 and 15 and in vitro fermentation was conducted with or without the addition of STS, respectively, followed by 16S rRNA amplicon sequencing and analysis of short-chain fatty acids (SCFAs) and gases. Notably, our results revealed that STS supplementation led to significant alterations in gut microbiota composition, including an increase in the abundance of beneficial bacteria such as Bifidobacterium and Faecalibacterium, and a decrease in harmful bacteria including Escherichia-Shigella, Parabacteroides, Eggerthella, and Flavonifractor. Moreover, STS supplementation resulted in changes in SCFAs production, with significant increases in acetate levels and reductions in propionate and propionate, while simultaneously reducing the generation of gases such as H2S, H2, and NH3. The Area Under the Curve (AUC)-Random Forest algorithm and PICRUSt 2 were employed to identify valuable biomarkers and predict associations between the gut microbiota, metabolites, and metabolic pathways. The results not only contribute to the elucidation of STS's modulatory effects on gut microbiota but also underscore its potential in shaping metabolic activities within the gastrointestinal environment. Furthermore, our study underscores the significance of personalized nutrition interventions, particularly utilizing STS supplementation, in the management of childhood obesity through targeted modulation of gut microbial ecology and metabolic function.

Sub-chronically exposing zebrafish to environmental levels of methomyl induces dysbiosis and dysfunction of the gut microbiota

The widespread use of carbamate pesticides has led to numerous environmental and health concerns, including water contamination and perturbation of endocrine homeostasis among organisms. However, there remains a paucity of research elucidating the specific effects of methomyl on gut microbial composition and physiological functions. This study aimed to investigate the intricate relationship between changes in zebrafish bacterial communities and intestinal function after 56 days of sub-chronic methomyl exposure at environmentally relevant concentrations (0, 0.05, 0.10, and 0.20 mg/L). Our findings reveal significant methomyl-induced morphological changes in zebrafish intestines, characterized by villi shortening and breakage. Notably, methomyl exposure down-regulated nutrient and energy metabolism, and drug metabolism at 0.05−0.10 mg/L, while up-regulating cortisol, inflammation-related genes, and apoptotic markers at 0.20 mg/L. These manifestations indicate physiological stress imposition and disruption of gut microbiota equilibrium, impacting metabolic processes and instigating low-grade inflammatory responses and apoptotic cascades. Importantly, changes in intestinal function significantly correlated with shifts in specific bacterial taxa abundance, including Shewanella, Rubrobacter, Acinetobacter, Bacillus, Luteolibacter, Nocardia, Defluviimonas, and Bacteroides genus. In summary, our study underscores the potential adverse effects of environmental methomyl exposure on aquatic organisms, emphasizing the necessity for further research to mitigate its repercussions on environmental health and ecosystem stability.

Distinct gut microbiomes in Thai patients with colorectal polyps.

Colorectal polyps that develop via the conventional adenoma-carcinoma sequence [e.g., tubular adenoma (TA)] often progress to malignancy and are closely associated with changes in the composition of the gut microbiome. There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway, such as hyperplastic polyps (HP). Exploration of microbiome alterations associated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis. To investigate gut microbiome signatures, microbial associations, and microbial functions in HP and TA patients. Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps [control group (CT), n = 40], patients with HP (n = 52), and patients with TA (n = 60). Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA. Analytical techniques in this study included differential abundance analysis, co-occurrence network analysis, and differential pathway analysis. Colorectal cancer (CRC)-associated bacteria, including Streptococcus gallolyticus (S. gallolyticus), Bacteroides fragilis, and Clostridium symbiosum, were identified as characteristic microbial species in TA patients. Mediterraneibacter gnavus, associated with dysbiosis and gastrointestinal diseases, was significantly differentially abundant in the HP and TA groups. Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively, whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis (e.g., mevalonate); S. gallolyticus was a major contributor. Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients, whereas TA patients exhibited co-occurrence of CRC-associated bacteria. Furthermore, the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients. This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development, providing insights concerning the roles of microbial species, functional pathways, and microbial interactions in colorectal carcinogenesis.

Enhancing gut microbiota and microbial function with inulin supplementation in children with obesity.

Gut dysbiosis that resulted from the alteration between host-microbe interaction might worsen obesity-induced systemic inflammation. Gut microbiota manipulation by supplementation of prebiotic inulin may reverse metabolic abnormalities and improve obesity. This study aimed to determine whether inulin supplementation improved intestinal microbiota and microbial functional pathways in children with obesity. Children with obesity whose BMI above median + 2SDs were recruited to a randomized, double-blinded placebo-controlled study. The participants aged 7-15 years were assigned to inulin supplement extracted from Thai Jerusalem artichoke (intervention), maltodextrin (placebo), and dietary fiber advice groups. All participants received similar monthly conventional advice and follow-up for 6 months. Fecal samples were collected for gut microbiome analysis using 16S rRNA sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was performed to infer microbial functional pathways. One hundred and forty-three children with available taxonomic and functional pathway abundance profiles were evaluated. A significant increase in alpha-diversity was observed in the inulin group. Inulin supplementation substantially enhanced Bifidobacterium, Blautia, Megasphaera, and several butyrate-producing bacteria, including Agathobacter, Eubacterium coprostanoligenes, and Subdoligranulum, compared to the other groups. The inulin group showed a significant difference in functional pathways of proteasome and riboflavin metabolism. These changes correlated with clinical and metabolic outcomes exclusively in the inulin group. Inulin supplementation significantly promoted gut bacterial diversity and improved gut microbiota dysbiosis in children with obesity. The modulation of functional pathways by inulin suggests its potential to establish beneficial interactions between the gut microbiota and host physiology. Inulin supplementation could be a strategic treatment to restore the balance of intestinal microbiota and regulate their functions in childhood obesity.

Probiotics administration alleviates cognitive impairment and circadian rhythm disturbance induced by sleep deprivation

Gut microbiome is indispensable for maintaining normal brain function. Specifically, gut microbiota plays a causal role in sleep deprivation (SD)-induced cognitive impairment. In this study, neurobehavioral effects of the Bifidobacterium breve strain (CCFM1025) were assessed in sleep-deprived mice. CCFM1025 improved the body weight and food and water intake of the mice. It also alleviated SD-induced cognitive behavioural abnormalities (in the novel object recognition test), but did not show beneficial effects on mood- and spatial memory-related behaviours. CCFM1025 significantly altered the gut microbial composition and genome function. Key microbial metabolites that may regulate sleep function were also identified, such as isovaleric acid and γ-aminobutyric acid in the gut and purine metabolites in the serum. Those metabolites may participate in gut-brain communication by acting on the striatal melatonin system, for example to increase melatonin levels, and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1. Collectively, administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites. These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.

Cadmium exposure induces changes in gut microbial composition and metabolic function in long-tailed dwarf hamsters, Cricetulus longicaudatus.

Numerous studies have demonstrated that exposure to cadmium disrupts the diversity and composition of the gut microbiota, resulting in damage to organ tissue. However, there remains a lack of comprehensive understanding regarding the broader ecological reality associated with this phenomenon. In this study, we conducted a thorough evaluation of the effects of different concentrations of Cd (6, 12, 24, and 48 mg/L) over a period of 35 consecutive days on the organ viscera and the gut microbiota of long-tailed dwarf hamsters, Cricetulus longicaudatus (Rodentia: Cricetidae), using histopathological analysis, 16S rDNA, and metagenome sequencing. Our findings revealed that the results suggest that Cd exposure induced liver, spleen, and kidney damage, potentially leading to increased intestinal permeability and inflammation. These alterations were accompanied by significant perturbations in the gut microbiota composition, particularly affecting potentially pathogenic bacteria such as Prevotella and Treponema within the gut ecosystem. Consequently, host susceptibility to underlying diseases was heightened due to these changes. Notably though, Cd exposure did not significantly impact the overall structure of the gut microbiota itself. Additionally, Cd exposure induced significant changes in the metabolic functions, with the pathways related to disease and environmental information processing notably enhanced, possibly indicating stronger innate defense mechanisms against external injuries among wild mammals exposed to Cd. This study offers a novel approach to comprehensively evaluate the significant impact of Cd pollution on ecosystems by investigating both structural and functional alterations in the digestive system, as well as disruptions in intestinal flora among wild mammals.

The diet-intestinal microbiota dynamics and adaptation in an elevational migration bird, the Himalayan bluetail (Tarsiger rufilatus).

Migratory birds experience changes in their environment and diet during seasonal migrations, thus requiring interactions between diet and gut microbes. Understanding the co-evolution of the host and gut microbiota is critical for elucidating the rapid adaptations of avian gut microbiota. However, dynamics of gut microbial adaptations concerning elevational migratory behavior, which is prevalent but understudied in montane birds remain poorly understood. We focused on the Himalayan bluetail (Tarsiger rufilatus) in the montane forests of Mt. Gongga to understand the diet-gut microbial adaptations of elevational migratory birds. Our findings indicate that elevational migratory movements can rapidly alter gut microbial composition and function within a month. There was a significant interaction between an animal-based diet and gut microbiota across migration stages, underscoring the importance of diet in shaping microbial communities. Furthermore, the gut microbial composition of T. rufilatus may be potentially altered by high-altitude acclimatization. An increase in fatty acid and amino acid metabolism was observed in response to low temperatures and limited resources, resulting in enhanced energy extraction and nutrient utilization. Moreover, microbial communities in distinct gut segments varied in relative abundance and responses to environmental changes. While the bird jejunum exhibited greater susceptibility to food and environmental fluctuations, there was no significant difference in metabolic capacity among gut segments. This study provides initial evidence of rapid diet-gut microbial changes in distinct gut segments of elevational migratory birds and highlights the importance of seasonal sample collection. Our findings provide a deeper understanding of the unique high-altitude adaptation patterns of the gut microbiota for montane elevational migratory birds.

Metaproteomic portrait of the healthy human gut microbiota

Gut metaproteomics can provide direct evidence of microbial functions actively expressed in the colonic environments, contributing to clarify the role of the gut microbiota in human physiology. In this study, we re-analyzed 10 fecal metaproteomics datasets of healthy individuals from different continents and countries, with the aim of identifying stable and variable gut microbial functions and defining the contribution of specific bacterial taxa to the main metabolic pathways. The “core” metaproteome included 182 microbial functions and 83 pathways that were identified in all individuals analyzed. Several enzymes involved in glucose and pyruvate metabolism, along with glutamate dehydrogenase, acetate kinase, elongation factors G and Tu and DnaK, were the proteins with the lowest abundance variability in the cohorts under study. On the contrary, proteins involved in chemotaxis, response to stress and cell adhesion were among the most variable functions. Random-effect meta-analysis of correlation trends between taxa, functions and pathways revealed key ecological and molecular associations within the gut microbiota. The contribution of specific bacterial taxa to the main biological processes was also investigated, finding that Faecalibacterium is the most stable genus and the top contributor to anti-inflammatory butyrate production in the healthy gut microbiota. Active production of other mucosal immunomodulators facilitating host tolerance was observed, including Roseburia flagellin and lipopolysaccharide biosynthetic enzymes expressed by members of Bacteroidota. Our study provides a detailed picture of the healthy human gut microbiota, contributing to unveil its functional mechanisms and its relationship with nutrition, immunity, and environmental stressors.

Secondary bile acids are associated with body lipid accumulation in obese pigs

The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs. The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation. Fourteen pigs, including seven lean and seven obese pigs with body weights of approximately 80 kg, were fed the same diet at an amount approximately equivalent to 3% of their respective body weights daily for 42 d. In vitro, 3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium. Then, bile acids were added to mature adipocytes for 4 d. The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs (P < 0.05). According to the results of gut microbial function prediction, the bile acid biosynthesis in colonic digesta of obese pigs were different from that in lean pig. Sixty-five bile acids were further screened by metabolomics, of which 4 were upregulated (P < 0.05) and 2 were downregulated (P < 0.05) in obese pigs compared to lean pigs. The results of the correlation analysis demonstrated that chenodeoxycholic acid-3-β-D-glucuronide (CDCA-3Gln) and ω-muricholic acid (ω-MCA) had a negative correlation with abdominal fat weight and abdominal fat rate, while isoallolithocholic acid (IALCA) was positively associated with crude fat in the liver and abdominal fat rate. There was a positive correlation between loin muscle area and CDCA-3Gln and ω-MCA (P < 0.05), however, IALCA and 3-oxodeoxycholic acid (3-oxo-DCA) were negatively associated with loin eye muscle area (P < 0.05). Isoallolithocholic acid increased the gene expression of peroxisome proliferator-activated receptor gamma (PPARG) and the number of lipid droplets (P < 0.05), promoting the lipid storage when IALCA was added to 3T3-L1 mature adipocytes in vitro. In conclusion, the concentration of bile acids, especially gut microbiota related-secondary bile acids, in obese pigs was different from that in lean pigs, which may contribute to lipid accumulation within obese pigs.

Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response.

Maternal obesity and/or Western diet (WD) is associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by the dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of Il10 (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition and was associated with a reduced abundance of Lactobacillus in GF offspring. Further, the expression of Il10 was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of Il10. Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, highlighting the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and the development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.

A Comprehensive Pilot Study to Elucidate the Distinct Gut Microbial Composition and Its Functional Significance in Cardio-Metabolic Disease.

Cardio-metabolic disease is a significant global health challenge with increasing prevalence. Recent research underscores the disruption of gut microbial balance as a key factor in disease susceptibility. We aimed to characterize the gut microbiota composition and function in cardio-metabolic disease and healthy controls. For this purpose, we collected stool samples of 18 subjects (12 diseased, 6 healthy) and we performed metagenomics analysis and functional prediction using QIIME2 and PICRUSt. Furthermore, we carried out assessments of microbe-gene interactions, gene ontology, and microbe-disease associations. Our findings revealed distinct microbial patterns in the diseased group, particularly evident in lower taxonomic levels with significant variations in 14 microbial features. The diseased cohort exhibited an enrichment of Lachnospiraceae family, correlating with obesity, insulin resistance, and metabolic disturbances. Conversely, reduced levels of Clostridium, Gemmiger, and Ruminococcus genera indicated a potential inflammatory state, linked to compromised butyrate production and gut permeability. Functional analyses highlighted dysregulated pathways in amino acid metabolism and energy equilibrium, with perturbations correlating with elevated branch-chain amino acid levels-a known contributor to insulin resistance and type 2 diabetes. These findings were consistent across biomarker assessments, microbe-gene associations, and gene ontology analyses, emphasizing the intricate interplay between gut microbial dysbiosis and cardio-metabolic disease progression. In conclusion, our study unveils significant shifts in gut microbial composition and function in cardio-metabolic disease, emphasizing the broader implications of microbial dysregulation. Addressing gut microbial balance emerges as a crucial therapeutic target in managing cardio-metabolic disease burden.