Host Gut Microbiota Research Articles

Genome-Wide and 16S rRNA Sequencing-Based Analysis on the Health Effects of Lacticaseibacillus paracasei XLK401 on Chicks.

Lacticaseibacillus paracasei, serves as a growth promoter used in the poultry industry, contributeing to broiler development. However, practical studies are needed to determine the probiotic potential and growth-promoting effects of specific L. paracasei strains. This study aims to determine whether L. paracasei XLK401 influences broiler chicken growth and the mechanisms involved. Notably, we identified several bile salt and acid tolerance-related genes (Asp23, atpD, atpA, atpH, and atpF) in L. paracasei XLK401. This bacterium demonstrates robust probiotic properties under acidic conditions (pH 2.0) and 0.3% bile salt conditions. It also contains a variety of antioxidant-related genes (trxA, trxB, and tpx), carbohydrate-related genes, gene-encoding glycosidases (e.g., GH and GT), and three clusters of genes associated with antimicrobial compounds. Supplementation with L. paracasei XLK401 significantly increased the body weight of the chicks. In addition, it significantly increased hepatic antioxidant enzyme activities (GSH-Px, SOD, and T-AOC) while significantly decreasing the levels of oxidative damage factors and inflammatory factors (MDA and IL-6), resulting in improved chick health. Improvements in body weight and health status were associated with significant increases in α-amylase activity and the remodeling of the host gut microbiota by L. paracasei XLK401. Among them, actinobacteria abundance in chicken intestines after feeding them L. paracasei XLK401 was significantly decreased, Bifidobacterium sp. abundance was also significantly decreased, and Subdoligranulum sp. abundance was significantly increased. This suggests that L. paracasei XLK401 can regulate the abundance of certain bacteria without changing the overall microbial structure. In addition, in the correlation analysis, Subdoligranulums sp. were positively correlated with SOD and negatively correlated with IL-1β and MDA. Overall, our study demonstrates that L. paracasei XLK401 effectively promotes healthy chick growth. This is made possible by the modulation of gut microbe abundance and the underlying probiotic effect of L. paracasei XLK401. Based on these findings, we postulate L. paracasei XLK401 as a potential efficient growth promoter in broiler farming.

Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis

Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged as distinct mechanistic pathways implicated in the development of NAFLD. Here, we report that a group of gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with the presence and severity of NAFLD. HDCA treatment has been shown to alleviate NAFLD in multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) and upregulating hepatic CYP7B1. Additionally, HDCA significantly increased abundances of probiotic species such as Parabacteroides distasonis, which enhances lipid catabolism through fatty acid-hepatic peroxisome proliferator-activated receptor alpha (PPARα) signaling, which in turn upregulates hepatic FXR. These findings suggest that HDCA has therapeutic potential for treating NAFLD, with a unique mechanism of simultaneously activating hepatic CYP7B1 and PPARα.

Effects of parasitism by a parasitoid wasp on the gut microbiota in a predaceous lady beetle host.

The gut microbiota has an intimate relationship with insect hosts and this relationship can become complicated with parasitic organisms being involved with the host. To date there has been limited evidence for the relevance of parasitism of the host by parasitoids to host gut microbiota, especially in host insect predators. Here, our study examined gut microbiotas in larvae of the predaceous lady beetle, Coccinella septempunctata, in response to their parasitism by Homalotylus eytelweinii regarding the development progress of offspring parasitoids. Overall 58.5% of gut bacterial operational taxonomic units (OTUs) in the parasitized lady beetle were different from those in the unparasitized host. The phylum Proteobacteria abundance increased while Firmicutes decreased in parasitized hosts compared to the unparasitized. The abundance of genus Aeribacillus decreased substantially in the parasitized lady beetle across all stages of the offspring development compared to the unparasitized host. The α-diversity of the gut microbiota in a parasitized lady beetle larva increased at the early stage of offspring parasitoids and then returned over the intermediate and later stages. Analyses of β-diversity indicated that the gut microbial community in a parasitized lady beetle was distinct from that in an unparasitized one and different between early or middle and late stages of offspring parasitoids in parasitized hosts. Our results provide evidence for the relevance of the gut microbiota to interactions between a lady beetle host and its parasitoid. Our study provides a starting point for further investigations of the role the gut microbiota may play in host-parasitoid interactions. © 2023 Society of Chemical Industry.

Probiotic Bacillus subtilis contributes to the modulation of gut microbiota and blood metabolic profile of hosts

Probiotic Bacillus subtilis has beneficial efficacy on host's health. The microbiota-gut-blood system (MGBS) plays a crucial role in maintaining the homeostasis of hosts. However, the mechanism by which the probiotic B. subtilis positively acts on the MGBS of hosts remains unclear. Herein, we used an interspecies animal model to explore the causal associations between this bacterium and the micro-ecology balance and circulatory homeostasis of hosts. Results showed that the body weight of hosts significantly increased after probiotic B. subtilis supplementation (P < 0.05). Enterococcus was found to be the most important microbial marker causing the intergroup differences observed herein, and its relative abundance remarkably increased after B. subtilis supplementation. In addition, the supplementation of B. subtilis induced significant alterations in the levels of circulating metabolites, such as serine, arginine, adenine, uric acid, and pyridoxal (P < 0.05), indicating that B. subtilis modulated the metabolic profile of blood circulation in the host. The metabolisms of amino acids, purine, and vitamin B were the primary pathways modulated by B. subtilis. In conclusion, probiotic B. subtilis substantially introduced subtle but positive changes in the host's gut microbiome, and it promoted the physiological activity of the host by modulating circulating metabolites. The study provides a theoretical reference for the application of probiotic B. subtilis to improve the health state of specific populations.

Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target.

A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk. We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.

NAD+ Precursors in Human Health and Disease: Current Status and Future Prospects.

Significance: Nicotinamide adenine dinucleotide (NAD+) acts as a cofactor in many important biological processes. The administration of NAD+ precursors increases the intracellular NAD+ pool and has beneficial effects on physiological changes and diseases associated with aging in various organisms, including rodents and humans. Recent Advances: Evidence from preclinical studies demonstrating the beneficial effects of NAD+ precursors has rapidly increased in the last decade. The results of these studies have prompted the development of clinical trials using NAD+ precursors, particularly nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). In addition, in vivo studies of NAD+ metabolism have rapidly progressed. Critical Issues: Several studies have demonstrated that the oral administration of NAD+ precursors, such as NR and NMN, is safe and significantly increases NAD+ levels in humans. However, the efficacy of these NAD+ precursors is lower than expected from the results of preclinical studies. In addition, the identification of the contribution of the host-gut microbiota interactions to NR and NMN metabolism has added to the complexity of NAD+ metabolism. Future Directions: Further studies are required to determine the efficacy of NAD+ precursors in humans. Further in vivo studies of NAD+ metabolism are required to optimize the effects of NAD+ supplementation. There is also a need for methods of delivering NAD+ precursors to target organs or tissues to increase the outcomes of clinical trials. Antioxid. Redox Signal. 39, 1133-1149.

Biglycan regulated colorectal cancer progress by modulating enteric neuron-derived IL-10 and abundance of Bacteroides thetaiotaomicron

Biglycan (BGN) is a proteoglycan with branch chains and highly expressed in enteric neurons in the tumor tissue of colorectal cancer (CRC), which is negatively associated with survival rates in patients with CRC. However, how the proteoglycan promotes the progress of CRC through interacting with bacteria and regulating the immune response of enteric neurons remains largely unknown. In the present study, we found that biglycan deficiency changed tumor distribution in a colitis-associated colon cancer model. Furthermore, we revealed that BGN deficiency inhibits tumor growth in an allograft tumor model and the migration of cancer cell by upregulating interleukin-10 expression in enteric neurons. Significantly, we demonstrated that biglycan deficiency enriched the abundance of Bacteroides thetaiotaomicron through competing with it for chondroitin sulfate to inhibit CRC progress. Our work provided new insights into the interaction between host proteoglycan and gut microbiota as well as the role of enteric neurons in the tumor microenvironment.

Transcriptome and the gut microbiome analysis of the impacts of Brucella abortus oral infection in BALB/c mice

Brucellosis is a zoonotic infectious disease caused by Brucella spp, which could cause serious economic losses to animal husbandry and threaten human public health. Ingestion of contaminated animal products is a common way to acquire Brucella infection in humans, while research on effect of oral Brucella infection on host gut microbiota and the gene expression in intestinal tissues is limited. In the present study, 16S rRNA sequencing and RNA sequencing were conducted to explore gut microbiota and expression profiles of mRNAs in the colon of BALB/c mice, which were infected by Brucella abortus 2308. The fecal samples were collected at 7 and 28 days post infection to observe changes in the gut microbiota during Brucella infection. In the alpha diversity analysis, significantly increased Chao 1 index was observed at 28 days after Brucella infection. The Bray–Curtis distancebased principal coordinate analysis indicated that the WT group showed a separation from the Brucella infection groups. In addition, analysis of composition of microbes revealed that Prevotellaceae_NK3B31_group were more abundant in 1 week and 4 week infection groups, while Turicibacter was only more abundant in 4 week infection group. Based on the RNA-seq assay, a total of 45 differentially expressed genes were detected between Brucella abortus infection group and control group. Furthermore, KEGG pathway enrichment analysis showed that protein processing in endoplasmic reticulum, Legionellosis, Spliceosome, Hippo signaling pathway and Influenza A were significantly enriched in response to Brucella abortus infection. Our finding will help to improve the knowledge of the mechanisms underlying Brucella infection and may provide novel targets for future treatment of this pathogen infection.

Palmitoylethanolamide counteracts high-fat diet-induced gut dysfunction by reprogramming microbiota composition and affecting tryptophan metabolism.

Obesity is associated with gastrointestinal (GI) tract and central nervous system (CNS) disorders. High-fat diet (HFD) feeding-induced obesity in mice induces dysbiosis, causing a shift toward bacteria-derived metabolites with detrimental effects on metabolism and inflammation: events often contributing to the onset and progression of both GI and CNS disorders. Palmitoylethanolamide (PEA) is an endogenous lipid mediator with beneficial effects in mouse models of GI and CNS disorders. However, the mechanisms underlining its enteroprotective and neuroprotective effects still need to be fully understood. Here, we aimed to study the effects of PEA on intestinal inflammation and microbiota alterations resulting from lipid overnutrition. Ultramicronized PEA (30 mg/kg/die per os) was administered to HFD-fed mice for 7 weeks starting at the 12th week of HFD regimen. At the termination of the study, the effects of PEA on inflammatory factors and cells, gut microbial features and tryptophan (TRP)-kynurenine metabolism were evaluated. PEA regulates the crosstalk between the host immune system and gut microbiota via rebalancing colonic TRP metabolites. PEA treatment reduced intestinal immune cell recruitment, inflammatory response triggered by HFD feeding, and corticotropin-releasing hormone levels. In particular, PEA modulated HFD-altered TRP metabolism in the colon, rebalancing serotonin (5-HT) turnover and reducing kynurenine levels. These effects were associated with a reshaping of gut microbiota composition through increased butyrate-promoting/producing bacteria, such as Bifidobacterium, Oscillospiraceae and Turicibacter sanguinis, with the latter also described as 5-HT sensor. These data indicate that the rebuilding of gut microbiota following PEA supplementation promotes host 5-HT biosynthesis, which is crucial in regulating intestinal function.

“Host-gut microbiota” interactions in a case of eubiosis and dysbiosis

This review consolidates the data of recent Russian and foreign research works, considering how gut microbiota composition and gut metabolites can affect metabolic disorders. From the standpoint of modern concepts, the authors discuss the functions of the immune system responsible for maintaining relationships with symbiotic microorganisms, analyze the accumulated information on the participation of metabolites of gut microflora in the development of pathological conditions. According to the results of the last two decades achieved, challenges ahead include translation of findings and mechanisms into clinical practice and development of therapeutic options and regimens that target metabolic risks by modulation of gut microbes and metabolites.

Uncovering the Carboxylated Metabolome in Gut Microbiota-Host Co-metabolism: A Chemical Derivatization-Molecular Networking Approach.

Gut microbiota-host co-metabolites serve as essential mediators of communication between the host and gut microbiota. They provide nutrient sources for host cells and regulate gut microenvironment, which are associated with a variety of diseases. Analysis of gut microbiota-host co-metabolites is of great significance to explore the host-gut microbiota interaction. In this study, we integrated chemical derivatization, liquid chromatography-mass spectrometry, and molecular networking (MN) to establish a novel CD-MN strategy for the analysis of carboxylated metabolites in gut microbial-host co-metabolism. Using this strategy, 261 carboxylated metabolites from mouse feces were detected, which grouped to various classes including fatty acids, bile acids, N-acyl amino acids, benzoheterocyclic acids, aromatic acids, and other unknown small-scale molecular clusters in MN. Based on the interpretation of the bile acid cluster, a novel type of phenylacetylated conjugates of host bile acids was identified, which were mediated by gut microbiota and exhibited a strong binding ability to Farnesoid X receptor and Takeda G protein-coupled receptor 5. Our proposed strategy offers a promising platform for uncovering carboxylated metabolites in gut microbial-host co-metabolism.

Altered gut microbiota–host bile acid metabolism in IBS-D patients with liver depression and spleen deficiency pattern

BackgroundDysregulation of gut microbiota–host bile acid (BA) co-metabolism is a critical pathogenic factor of diarrhea-predominant irritable bowel syndrome (IBS-D). Traditional Chinese Medicine (TCM), instructed by pattern differentiation, is effective in treating IBS-D, in which liver depression and spleen deficiency (LDSD) is the most prevalent pattern. Still, it is unclear the linkage between the LDSD pattern and the BA metabolic phenotype.PurposeThis study aimed to uncover the biological basis of the LDSD pattern from the BA metabolic perspective.MethodsPatients with IBS-D completed questionnaires regarding the irritable bowel severity scoring system (IBS-SSS), stool frequency, Stool Bristol scale, and Self-Rating Scales of mental health. Fasting blood and morning feces were collected to analyze the gut metagenome and BA-related indices/metabolites.ResultsIBS-D patients with LDSD had a higher incidence of BA overexcretion (41% vs. 23% non-LDSD) with significant elevations in fecal total BAs and serum BA precursor 7α-hydroxy-4-cholesten-3-one levels. Compared to controls or non-LDSD patients, LDSD patients had a featured fecal BA profile, with higher proportions of deoxycholic acid (DCA), 7-ketodeoxycholic acid, and lithocholic acid. It is consistent with the BA-metabolizing genomic changes in the LDSD gut microbiota characterized by overabundances of 7-dehydroxylating bacteria and BA-inducible genes (baiCD/E/H). The score of bowel symptoms (stool frequency and abdominal pain) showing greater severity in the LDSD pattern were positively correlated with bai-expressing bacterial abundances and fecal DCA levels separately.ConclusionWe clarified a differed BA metabolic phenotype in IBS patients with LDSD, which closely correlates with the severity of bowel symptoms. It demonstrates that gut microbiota and host co-metabolism of BAs would provide crucial insight into the biology of the LDSD pattern and its internal relationship with IBS progression.

High-fat diet-disturbed gut microbiota-colonocyte interactions contribute to dysregulating peripheral tryptophan-kynurenine metabolism

BackgroundAberrant tryptophan (Trp)-kynurenine (Kyn) metabolism has been implicated in the pathogenesis of human disease. In particular, populations with long-term western-style diets are characterized by an excess of Kyn in the plasma. Host-gut microbiota interactions are dominated by diet and are essential for maintaining host metabolic homeostasis. However, the role of western diet-disturbed gut microbiota-colonocyte interactions in Trp metabolism remains to be elucidated.ResultsHere, 4-week-old mice were fed with a high-fat diet (HFD), representing a typical western diet, for 4 weeks, and multi-omics approaches were adopted to determine the mechanism by which HFD disrupted gut microbiota-colonocyte interplay causing serum Trp-Kyn metabolism dysfunction. Our results showed that colonocyte-microbiota interactions dominated the peripheral Kyn pathway in HFD mice. Mechanistically, persistent HFD-impaired mitochondrial bioenergetics increased colonic epithelial oxygenation and caused metabolic reprogramming in colonites to support the expansion of Proteobacteria in the colon lumen. Phylum Proteobacteria-derived lipopolysaccharide (LPS) stimulated colonic immune responses to upregulate the indoleamine 2,3-dioxygenase 1 (IDO1)-mediated Kyn pathway, leading to Trp depletion and Kyn accumulation in the circulation, which was further confirmed by transplantation of Escherichia coli (E.coli) indicator strains and colonic IDO1 depletion. Butyrate supplementation promoted mitochondrial functions in colonocytes to remodel the gut microbiota in HFD mice, consequently ameliorating serum Kyn accumulation.ConclusionsOur results highlighted that HFD disrupted the peripheral Kyn pathway in a gut microbiota-dependent manner and that the continuous homeostasis of gut bacteria-colonocytes interplay played a central role in the regulation of host peripheral Trp metabolism. Meanwhile, this study provided new insights into therapies against western diet-related metabolic disorders.24aEGHfcpJRSeLcqMKL4VcVideo

Dysbiosis of gut microbiota by actual long-term exposure to textile wastewater treatment plant effluents in adult zebrafish (Danio rerio) using aquatic microcosm systems

In the future, textile industry wastewater may create greater possibilities of releasing emerging contaminants into aquatic environments. Research on textile dyeing wastewater has focused on its adverse effects on biota. However, the effects of textile wastewater on gut microbiome and host health have not yet been elucidated, especially for the toxic assessment of combined pollutants under receiving water environment conditions. During this study, adult zebrafish were exposed to realistic textile wastewater treatment plant (TWTP) effluents in aquatic microcosm systems (AMS) for six months, a histopathological examination was performed, after which 16S rRNA and metagenomic sequencing of the intestinal microbiota was conducted and fish growth performance was also examined. As a result of exposure to TWTP effluents, adult zebrafish growth was significantly inhibited, the condition factor was exacerbated, and mortality was significantly increased. Also, significant alterations were observed in zebrafish guts after chronic exposure, which are the opportunistic pathogens Flavobacterium, Aeromonas, and Escherichia. The chronic effects of increased probiotic Cetobacterium, Bacteroides, and Planctomyces deserve further attention. Metagenomic sequencing also showed that genes of core metabolism pathways were affected by TWTP effluent exposure. The study has, for the first time, demonstrated gut microbiota's susceptibility and host health of adult zebrafish to TWTP effluents using aquatic microcosm systems, which are assumed to be clean, thus warranting additional research to reveal their mode of toxicity.

Fecal microbiota transplantation: A new strategy to delay aging

The gut microbiota, the community of gut microorganisms that inhabit the gastrointestinal tract, plays a crucial role in modulating host immunity, metabolism, and neurological health, thereby influencing the entire organism. Aging is associated with changes in gut microbiota composition and functionality, often resulting in dysbiosis, an imbalance of gut microbiota and an aging hallmark. Recent studies have suggested that fecal microbiota transplantation (FMT), the transfer of fecal material containing beneficial microbes from a healthy donor to a recipient with a disturbed microbiota, may restore the balance of host gut microbiota and ameliorate some aging-associated impairments in diverse organs. In particular, FMT from young donors has shown more beneficial effects than FMT from aged donors. In this paper, we review recent advances in FMT for its effects on aging and discuss the potential mechanisms and challenges of this novel intervention, highlighting its potential to improve health outcomes in the aging population.

From probiotics to postbiotics: Concepts and applications

AbstractIn recent years, the important role of gut microbiota in promoting animal health and regulating immune function in livestock and poultry has been widely reported. The issue of animal health problems causes significant economic losses each year. Probiotics and postbiotics have been widely developed as additives due to their beneficial effects in balancing host gut microbiota, enhancing intestinal epithelial barrier, regulating immunity, and whole‐body metabolism. Probiotics and postbiotics are composed of complex ingredients, with different components and compositions having different effects, requiring classification for discussing their mechanisms of action. Probiotics and postbiotics have considerable prospects in preventing various diseases in the livestock industry and animal feed and medical applications. This review highlights the application value of probiotics and postbiotics as potential probiotic products, emphasizing their concept, mechanism of action, and application, to improve the productivity of livestock and poultry.

Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery

BackgroundMost interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother–offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important disruptive factor of this transfer. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation in a murine model of CSD.ResultsThe higher sensitivity to chemically induced inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the pup’s immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early life involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex-germ-free mice colonized by CSD pups’ microbiota.ConclusionsEarly-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice.BBJL6KRzb7pAFtZtZ-zX7MVideo

Short-Term Clinical Response and Changes in the Fecal Microbiota and Metabolite Levels in Patients with Crohn's Disease After Stem Cell Infusions.

Recent studies have shown a close relationship between the gut microbiota and Crohn's disease (CD). This study aimed to determine whether mesenchymal stem cell (MSC) treatment alters the gut microbiota and fecal metabolite pathways and to establish the relationship between the gut microbiota and fecal metabolites. Patients with refractory CD were enrolled and received 8 intravenous infusions of MSCs at a dose of 1.0 × 106 cells/kg. The MSC efficacy and safety were evaluated. Fecal samples were collected, and their microbiomes were analyzed by 16S rDNA sequencing. The fecal metabolites at baseline and after 4 and 8 MSC infusions were identified by liquid chromatography-mass spectrometry (LC--MS). A bioinformatics analysis was conducted using the sequencing data. No serious adverse effects were observed. The clinical symptoms and signs of patients with CD were substantially relieved after 8 MSC infusions, as revealed by changes in weight, the CD activity index (CDAI) score, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). Endoscopic improvement was observed in 2 patients. A comparison of the gut microbiome after 8 MSC treatments with that at baseline showed that the genus Cetobacterium was significantly enriched. Linoleic acid was depleted after 8 MSC treatments. A possible link between the altered Cetobacterium abundance and linoleic acid metabolite levels was observed in patients with CD who received MSCs. This study enabled an understanding of both the gut microbiota response and bacterial metabolites to obtain more information about host-gut microbiota metabolic interactions in the short-term response to MSC treatment.

Porphyromonas gingivalis exacerbates alcoholic liver disease by altering gut microbiota composition and host immune response in mice.

Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, increases the risk of systemic diseases. P. gingivalis infection is closely associated with alcoholic liver disease (ALD), but the underlying mechanism remains unclear. We aimed to investigate the role of P. gingivalis in the pathogenesis of ALD. An ALD mouse model was established using a Lieber-DeCarli liquid diet, and C57BL/6 mice were treated with P. gingivalis to detect the pathological indicators of ALD. Oral administration of P. gingivalis exacerbated alcohol-induced alterations in the gut microbiota, leading to gut barrier dysfunction and inflammatory response and disruption of the T-helper 17 cell/T-regulatory cell ratio in the colon of ALD mice. Furthermore, P. gingivalis worsened liver inflammation in ALD mice by increasing the protein expression of toll-like receptor 4 (TLR4) and p65, increasing the mRNA expression of interleukins-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) and up-regulating the transforming growth factor-beta 1 (TGF-β1) and galectin-3 (Gal-3) production. These results indicate that P. gingivalis accelerates the pathogenesis of ALD via the oral-gut-liver axis, necessitating a new treatment strategy for patients with ALD complicated by periodontitis.

Deletion of hepatic growth hormone receptor (GHR) alters the mouse gut microbiota by affecting bile acid metabolism

ABSTRACT Both growth hormone (GH) and gut microbiota play significant roles in diverse physiological processes, but the crosstalk between them is poorly understood. Despite the regulation of GH by gut microbiota, study on GH’s influence on gut microbiota is limited, especially on the impacts of tissue specific GH signaling and their feedback effects on the host. In this study, we profiled gut microbiota and metabolome in tissue-specific GHR knockout mice in the liver (LKO) and adipose tissue (AKO). We found that GHR disruption in the liver rather than adipose tissue affected gut microbiota. It changed the abundance of Bacteroidota and Firmicutes at phylum level as well as abundance of several genera, such as Lactobacillus, Muribaculaceae, and Parasutterella, without affecting α-diversity. Moreover, the impaired liver bile acid (BA) profile in LKO mice was strongly associated with the change of gut microbiota. The BA pools and 12-OH BAs/non-12-OH BAs ratio were increased in the LKO mice, which was due to the induction of CYP8B1 by hepatic Ghr knockout. Consequently, the impaired BA pool in cecal content interacted with gut bacteria, which in turn increased the production of bacteria derived acetic acid, propionic acid, and phenylacetic acid that were possible to participate in the impaired metabolic phenotype of the LKO mice. Collectively, our findings suggested that the liver GH signaling regulates BA metabolism by its direct regulation on CYP8B1, which is an important factor influencing gut microbiota. Our study is significant in exploring gut microbiota modification effects of tissue-specific GH signaling as well as its involvement in gut microbiota–host interaction.