Composition Of Gut Bacteria Research Articles

Comparative study of the gut microbial community structure of Spodoptera frugiperda and Spodoptera literal (Lepidoptera).

Spodoptera frugiperda, the fall armyworm is a destructive invasive pest, and S. litura the tobacco cutworm, is a native species closely related to S. frugiperda. The gut microbiota plays a vital role in insect growth, development, metabolism and immune system. Research on the competition between invasive species and closely related native species has focused on differences in the adaptability of insects to the environment. Little is known about gut symbiotic microbe composition and its role in influencing competitive differences between these two insects. We used a culture-independent approach targeting the 16S rRNA gene of gut bacteria of 5th instar larvae of S. frugiperda and S. litura. Larvae were reared continuously on maize leaves for five generations. We analyzed the composition, abundance, diversity, and metabolic function of gut microbiomes of S. frugiperda and S. litura larvae. Firmicutes, Proteobacteria, and Bacteroidetes were the dominant bacterial phyla in both species. Enterococcus, ZOR0006, Escherichia, Bacteroides, and Lactobacillus were the genera with the highest abundance in S. frugiperda. Enterococcus, Erysipelatoclostridium, ZOR0006, Enterobacter, and Bacteroides had the highest abundance in S.litura. According to α-diversity analysis, the gut bacterial diversity of S. frugiperda was significantly higher than that of S.litura. KEGG analysis showed 15 significant differences in metabolic pathways between S. frugiperda and S. litura gut bacteria, including transcription, cell growth and death, excretory system and circulatory system pathways. In the same habitat, the larvae of S. frugiperda and S. litura showed significant differences in gut bacterial diversity and community composition. Regarding the composition and function of gut bacteria, the invasive species S. frugiperda may have a competitive advantage over S. litura. This study provides a foundation for developing control strategies for S. frugiperda and S. litura.

Brewers’ spent grain as fish feed ingredient: Evaluation of bio-safety and analysis of its impact on gut bacteria of Cirrhinus reba by 16S Metagenomic sequencing

A comprehensive eight week feeding trial was conducted to investigate the potential of brewers' spent grain (BSG) as a sustainable fish feed ingredient. The study assessed both the biosafety of BSG and its impact on the gut microbiome of Cirrhinus reba, utilizing advanced 16S metagenomic sequencing techniques to analyze the composition and diversity of gut bacteria. A total of 90 healthy C. reba juveniles (average weight: 12 ± 1 g) were divided into two dietary groups [for control (C), for BSG meal (tB)] in triplicates. Feed prepared with conventional ingredients was used to feed the control group (C). The group tB was fed with BSG meal. After the feeding trial, the fish in tB group showed significantly higher (p < 0.05) growth parameters as compared to the control group. The results of bio-safety assessment indicated the absence of any pathological symptoms in the BSG meal fed carps. The fish in tB group didn't show any histopathological abnormality. Fish fed the Brewers' Spent Grain exhibited significantly elevated serum biochemical parameters, including alanine transaminase (ALT) and aspartate transaminase (AST), compared to the control group (p < 0.05). 16S Metagenomic sequencing of the fish gut microbiota provides insights into how BSG inclusion affects microbial diversity and composition within the digestive tract of C. reba. The analysis revealed the existence of 240 and 250 diverse bacterial genera in the gastrointestinal tract (GIT) of C. reba in dietary groups C and tB respectively. Importantly, the study found the gut of fish in tB group to be dominated by different beneficial genus including Bacillus, Lactobacillus, Bifidobacterium, Paenibacillus, and Lysinibacillus. Feeding C. reba with BSG meal significantly increased the alpha diversity of the gastrointestinal microbiota, as evidenced by elevated Chao 1 estimator and Shannon index values compared to the control diet (p < 0.05). This study provides comprehensive evidence for the bio-safety of BSG as a sustainable feed ingredient in aquaculture, demonstrating its potential to support healthy fish growth and development. Moreover, the prebiotic potential of BSG in fish has also been highlighted.

Gut dysbacteriosis induces expression differences in the adult head transcriptome of Spodoptera frugiperda in a sex-specific manner

Mounting evidence indicates that the gut microbiota influences the neurodevelopment and behavior of insects through the gut-brain axis. However, it is currently unclear whether the gut microbiota affect the head profiles and immune pathway in pests. Here, we find that gut bacteria is essential for the immune and neural development of adult Spodoptera frugiperda, which is an extremely destructive agricultural pest worldwide. 16 S rRNA sequencing analysis showed that antibiotics exposure significantly disturbed the composition and diversity of gut bacteria. Further transcriptomic analysis revealed that the adult head transcripts were greatly affected by gut dysbacteriosis, and differently expression genes critical for brain and neural development including A4galt, Tret1, nsun4, Galt, Mitofilin, SLC2A3, snk, GABRB3, Oamb and SLC6A1 were substantially repressed. Interestingly, the dysbacteriosis caused sex-specific differences in immune response. The mRNA levels of pll (serine/threonine protein kinase Pelle), PGRP (peptidoglycan-sensing receptor), CECA (cecropin A) and CECB (cecropin B) involved in Toll and Imd signaling pathway were drastically decreased in treated male adults’ heads but not in female adults; however, genes of HIVEP2, ZNF131, inducible zinc finger protein 1-like and zinc finger protein 99-like encoding zinc-finger antiviral protein (ZAP) involved in the interferon (IFNα/β) pathway were significantly inhibited in treated female adults’ heads. Collectively, these results demonstrate that gut microbiota may regulate head transcription and impact the S. frugiperda adults’ heads through the immune pathway in a sex-specific manner. Our finding highlights the relationship between the gut microbiota and head immune systems of S. frugiperda adults, which is an astonishing similarity with the discoveries of other animals. Therefore, this is the basis for further research to understand the interactions between hosts and microorganisms via the gut-brain axis in S. frugiperda and other insects.

The Correlation between the Gut Microbiota of Endoclita signifer (Lepidoptera, Hepialidae) Larvae and Their Host Preferences.

Insects' gut microbiota plays a crucial role in their host selection, adaptation, and plasticity. This study explored the impact of gut bacteria on the adaptation of host selection under different stresses (diverse feeding preferences and no feeding preferences). The seventh instar E. signifer larvae were artificially transferred from the most-selected host E. grandis × E. urophylla (Es) to more preferred hosts, M. apelta (Ma), as well as the non-preferred host, B. papyrifera (Bp). We then obtained the larval gut of three different feeding preference hosts. The gut bacterial DNA was sequenced and analyzed based on 16S rRNA. There were significant differences in the composition of dominant gut bacteria between Es with Ma and Bp, but without significant differences between Ma and Bp. In the process, Burkholderia and Microbacillus with degrading pesticides had significant changes, and Enterococcus with insect gut probiotics also had significant changes. The presence of enterococcus may be one of the main causes of intestinal microbiota changes before and after host transfer. Notably, when the feeding of E. signifer changes, the complex connections that exist between gut bacteria also change. Additionally, there was a negative correlation between the feeding preferences of E. signifer and the metabolic functions of their gut bacteria. This study provided a theoretical basis for the prediction and use of gut bacteria to interfere with the feeding of E. signifer.

α-Synuclein expression in response to bacterial ligands and metabolites in gut enteroendocrine cells: an in vitro proof of concept study.

Caudo-rostral migration of pathological forms of α-synuclein from the gut to the brain is proposed as an early feature in Parkinson's disease pathogenesis, but the underlying mechanisms remain unknown. Intestinal epithelial enteroendocrine cells sense and respond to numerous luminal signals, including bacterial factors, and transmit this information to the brain via the enteric nervous system and vagus nerve. There is evidence that gut bacteria composition and their metabolites change in Parkinson's disease patients, and these alterations can trigger α-synuclein pathology in animal models of the disorder. Here, we investigated the effect of toll-like receptor and free fatty acid receptor agonists on the intracellular level of α-synuclein and its release using mouse secretin tumour cell line 1 enteroendocrine cells. Secretin tumour cell line 1 enteroendocrine cells were treated for 24 or 48 h with toll-like receptor agonists (toll-like receptor 4 selective lipopolysaccharide; toll-like receptor 2 selective Pam3CysSerLys4) and the free fatty acid receptor 2/3 agonists butyrate, propionate and acetate. The effect of selective receptor antagonists on the agonists' effects after 24 hours was also investigated. The level of α-synuclein protein was measured in cell lysates and cell culture media by western blot and enzyme-linked immunosorbent assay. The level of α-synuclein and tumour necrosis factor messenger RNA was measured by quantitative reverse transcription real-time polymerase chain reaction. Stimulation of secretin tumour cell line 1 enteroendocrine cells for 24 and 48 hours with toll-like receptor and free fatty acid receptor agonists significantly increased the amount of intracellular α-synuclein and the release of α-synuclein from the cells into the culture medium. Both effects were significantly reduced by antagonists selective for each receptor. Toll-like receptor and free fatty acid receptor agonists also significantly increased tumour necrosis factor transcription, and this was effectively inhibited by corresponding antagonists. Elevated intracellular α-synuclein increases the likelihood of aggregation and conversion to toxic forms. Factors derived from bacteria induce α-synuclein accumulation in secretin tumour cell line 1 enteroendocrine cells. Here, we provide support for a mechanism by which exposure of enteroendocrine cells to specific bacterial factors found in Parkinson's disease gut dysbiosis might facilitate accumulation of α-synuclein pathology in the gut.

Optimizing Fecal Occult Blood Test (FOBT) Colorectal Cancer Screening Using Gut Bacteriome as a Biomarker

BackgroundColorectal cancer (CRC) is a major cause of cancer mortality in the world. One of the most widely used screening tests for CRC is the immunochemical fecal occult blood test (iFOBT), which detects human hemoglobin from patient's stool sample. Although it is highly efficient in detecting blood from patients with gastro-intestinal lesions, such as polyps and cancers, the iFOBT has a high rate of false positive discovery. Recent studies suggested gut bacteria as a promising noninvasive biomarker for improving the diagnosis of CRC. In this study, we examined the composition of gut bacteria using iFOBT leftover from patients undergoing screening test along with a colonoscopy. MethodsAfter collecting data from more than 800 patients, we considered 4 groups for this study. The first and second groups were respectively “healthy” in which the patients had either no blood in their stool or had blood but no lesions. The third and fourth groups of patients had both blood in their stools with precancerous and cancerous lesions and considered either as low-grade and high-grade lesion groups, respectively. An amplification of 16S rRNA (V4 region) gene was performed, followed by sequencing along with various statistical and bioinformatic analysis. ResultsWe analyzed the composition of the gut bacteriome at phylum, class, genus, and species levels. Although members of the Firmicute phylum increased in the 3 groups compared to healthy patients, the phylum Actinobacteriota was found to decrease. Moreover, Blautia obeum and Anaerostipes hadrus from the phylum Firmicutes were increased and Collinsella aerofaciens from phylum Actinobacteriota was found decreased when healthy group is compared to the patients with high-grade lesions. Finally, among the 5 machine learning algorithms used to perform our analysis, both elastic net (AUC > 0.7) and random forest (AUC > 0.8) performs well in differentiating healthy patients from 3 other patient groups having blood in their stool. ConclusionOur study integrates the iFOBT screening tool with gut bacterial composition to improve the prediction of CRC lesions.

Gut flora alterations among aquatic firefly Aquatica leii inhabiting various dissolved oxygen in fresh water

Knowledge about the impact of different dissolved oxygen (DO) on the composition and function of gut bacteria of aquatic insects is largely unknown. Herein, we constructed freshwater environments with different DOs (hypoxia: 2.50± 0.50, normoxia: 7.00± 0.50, and hyperoxia: 13.00± 0.50mg/L) where aquatic firefly Aquatica leii larvae lived for three months. Their gut flora was analyzed using the combination of 16S rRNA amplicon sequencing and metagenomics. The results showed no difference in alpha diversity of the gut flora between A.leii inhabiting various DOs. However, the relative abundance of several bacterial lineages presented significant changes, such as Pseudomonas. In addition, bacterial genes with an altered relative abundance in response to various DOs were primarily related to metabolism. The alteration of these functions correlated with the DO change. This is the first to uncover structure of gut flora under various DOs in aquatic insect larvae.

Gut Microbiota Metabolites Mediate Bax to Reduce Neuronal Apoptosis via cGAS/STING Axis in Epilepsy.

The beneficial effects of gut flora on reducing nerve cell apoptosis and inflammation and improving epilepsy (EP) symptoms have been reported, but the specific mechanism of action is still unclear. A series of in vitro and in vivo experiments revealed the relationship between gut microbiota metabolites and the cGAS/STING axis and their role in EP. These results suggest that antibiotic-induced dysbiosisof gutmicrobiotaexacerbatedepilepticsymptoms, probiotic supplements reduced epileptic symptoms in mice. Antibiotics and probiotics altered the diversityandcompositionofgutmicrobiota. The changes in gut bacteria composition, such as in the abundance of Firmicutes, Bacteroidetes, Lactobacillus and Ruminococcus, were associated with the production of short-chain fatty acids (SCFA) in the gut. The concentrations of propionate, butyrate and isovalerate were changed after feeding antibiotics and probiotics, and the increase in butyrate levels reduced the expression of cGAS/STING in nerve cell further reduced Bax protein expression. The reduction of Bax protein attenuated the hippocampal neuron cell apoptosis in PTZ-induced EP and EP progression. Our findings provide new insights into the roles and mechanisms of action of the gut microbiota in attenuating EP symptoms and progression.

Features of combined gut bacteria and fungi from a Chinese cohort of colorectal cancer, colorectal adenoma, and post-operative patients.

Colorectal cancer (CRC) accounts for the third highest morbidity burden among malignant tumors worldwide. Previous studies investigated gut microbiome changes that occur during colorectal adenomas (CRA) progression to overt CRC, thus highlighting the importance of the gut microbiome in carcinogenesis. However, few studies have examined gut microbiome characteristics across the entire spectrum, from CRC development to treatment. The study used 16S ribosomal ribonucleic acid and internal transcribed spacer amplicon sequencing to compare the composition of gut bacteria and fungi in a Chinese cohort of healthy controls (HC), CRC patients, CRA patients, and CRC postoperative patients (PP). Our analysis showed that beta diversity was significantly different among the four groups based on the gut bacterial and fungal data. A total of 51 species of bacteria and 8 species of fungi were identified in the HC, CRA, CRC, and PP groups. Correlation networks for both the gut bacteria and fungi in HC vs. CRA, HC vs. CRC, and HC vs. PP indicated some hub bacterial and fungal genera in each model, and the correlation between bacterial and fungal data indicated that a highly significant negative correlation exists among groups. Quantitative polymerase chain reaction (qPCR) analysis in a large cohort of HC, CRC, CRA, and PP patients demonstrated a significantly increasing trend of Fusobacterium nucleatum, Bifidobacterium bifidum, Candida albicans, and Saccharomyces cerevisiae in the feces of CRC patients than that of HC patients (p < 0.01). However, the abundance levels of CRA and PP were significantly lower in HC patients than those in CRC patients. Further studies are required to identify the functional consequences of the altered bacterial/fungal composition on metabolism and CRC tumorigenesis in the host.

The Gut Microbiota - Brain Axis: Potential Mechanism of Drug Addiction.

As a chronic encephalopathy, drug addiction is responsible for millions of deaths per year around the world. The gut microbiome is a crucial component of the human microbiome. Through dynamic bidirectional communication along the 'gut-brain axis,' gut bacteria cooperate with their hosts to regulate the development and function of the immune, metabolic, and nervous systems. These processes may affect human health because some brain diseases are related to the composition of gut bacteria, and disruptions in microbial communities have been implicated in neurological disorders. We review the compositional and functional diversity of the gut microbiome in drug addiction. We discuss intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems and possible contributions by the gut microbiota to neurological disorders. Finally, the treatment of probiotics and fecal transplantation was summarized. This was done to further understand the role of intestinal microecology in the pathogenesis of drug addiction and to explore new methods for the treatment of drug addiction.

Exploring the Role of Mentha in Gut Microbiota: A Modern Perspective of an Ancient Herb.

Gut microbiota includes the microbes present in the gut; these microbes are an essential component in maintaining a healthy gut. Gut microbiota has a wide range of functions, including effects on colonization, pathogen resistance, intestinal epithelial maintenance, metabolizing food and pharmaceutical chemicals, and influencing immunological functions. Every disease associated with the gut starts due to a disbalance in the composition of the gut microorganisms and can be managed by balancing the composition of gut bacteria using various herbal remedies. Mentha herbs are a variety of perennial herbs that are grown commercially in various parts of the world. Mentha is a potent herb that shows anticholinergic action and can block PGE2 and GM1 receptors and interact with cholera toxins; it is used traditionally in different systems of medicines to treat various gastrointestinal diseases associated with the gut. Mentha herbs have potent bactericidal, viricidal, and fungicidal properties. Mentha has been used to cure stomach and digestion issues as well as to treat a variety of disorders. This review article summarizes diseases associated with the gut, the composition, and function of gut microbiota, and mentha's effectiveness along with its extraction methods and traditional uses. Research findings have revealed mentha to be an essential source against a wide range of diseases, especially gastrointestinal disorders. From its ayurvedic claims to its present use, it has been confirmed to be clinically effective for human health. Mentha-based products are marketed in the form of oils, capsules, powder, etc. The present work describes the mechanism of action along with the bioactives present in this well-known herb from Ayurveda.

Short-chain fatty acids in cancer pathogenesis.

Cancer is a multi-step process that can be viewed as a cellular and immunological shift away from homeostasis in response to selected infectious agents, mutations, diet, and environmental carcinogens. Homeostasis, which contributes importantly to the definition of "health," is maintained, in part by the production of short-chain fatty acids (SCFAs), which are metabolites of specific gut bacteria. Alteration in the composition of gut bacteria, or dysbiosis, is often a major risk factor for some two dozen tumor types. Dysbiosis is often characterized by diminished levels of SCFAs in the stool, and the presence of a "leaky gut," permitting the penetration of microbes and microbial derived molecules (e.g., lipopolysaccharides) through the gut wall, thereby triggering chronic inflammation. SCFAs attenuate inflammation by inhibiting the activation of nuclear factor kappa B, by decreasing the expression of pro-inflammatory cytokines such as tumor necrosis factor alpha, by stimulating the expression of anti-inflammatory cytokines such as interleukin-10 and transforming growth factor beta, and by promoting the differentiation of naïve T cells into T regulatory cells, which down-regulate immune responses by immunomodulation. SCFA function epigenetically by inhibiting selected histone acetyltransferases that alter the expression of multiple genes and the activity of many signaling pathways (e.g., Wnt, Hedgehog, Hippo, and Notch) that contribute to the pathogenesis of cancer. SCFAs block cancer stem cell proliferation, thereby potentially delaying or inhibiting cancer development or relapse by targeting genes and pathways that are mutated in tumors (e.g., epidermal growth factor receptor, hepatocyte growth factor, and MET) and by promoting the expression of tumor suppressors (e.g., by up-regulating PTEN and p53). When administered properly, SCFAs have many advantages compared to probiotic bacteria and fecal transplants. In carcinogenesis, SCFAs are toxic against tumor cells but not to surrounding tissue due to differences in their metabolic fate. Multiple hallmarks of cancer are also targets of SCFAs. These data suggest that SCFAs may re-establish homeostasis without overt toxicity and either delay or prevent the development of various tumor types.

Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism

ABSTRACT Intestinal stem cells (ISCs) are critical for the development and rapid turnover of intestinal epithelium. The regulatory effects of gut microbiota and their metabolites on ISCs stemness remain elusive. Fucose has been demonstrated to mediate host–microbe interactions in the intestine. However, the association between fucose, gut bacteria, and ISCs stemness remains unclear. To investigate the effects of fucose on ISCs-mediated intestinal epithelial cells (IECs) development, we administered fucose to 4-week-old mice for 4 weeks. ISCs stemness, IECs proliferation, and differentiation were examined. Variations in gut microbes and metabolism were detected using 16S rDNA sequencing and metabolomic analysis. Fucose was added to the bacterial culture medium to further study its effects on metabolism. Crypts were isolated from the mouse ileum for organoids culture in vitro to evaluate the effects of metabolites and the underlying mechanism. The results showed that fucose accelerated ISCs proliferation and secretory lineage differentiation in mice, whereas antibiotics eliminated these effects. The composition and functions of gut bacteria were altered by fucose treatment, while significant increases in Akkermansia and propanoate metabolism were noted. Propionic acid and propionate have been shown to promote organoid development. Fucose fermentation increases the production of propionic acid in Akkermansia muciniphila and enhances its ability to increase the stemness of ISCs. Moreover, ileal contents from fucose-treated mice promoted organoid development in a Gpr41/Gpr43-dependent manner. Fucose administration activates the Wnt signaling pathway in ISCs, and Wnt inhibitors suppress the effects of fucose. We conclude that fucose accelerates ISC-mediated intestinal epithelial development by promoting Akkermansia-related propanoate metabolism. These findings provide new insights into the promotion of gut homeostasis and the application potential of fucose as a prebiotic.

Gut bacteria and sex differences in colorectal cancer.

Introduction. Differences in gut bacteria that are associated with the occurrence and development of colorectal cancer (CRC) exist between sexes, and males have a higher morbidity of CRC.Gap Statement. Clinical data for the relationship between gut bacteria and sexes in patients with CRC are not available and are needed to support individualized screening and treatment programmes.Aim. To analyse the relationship between gut bacteria and sexes in patients with CRC.Methodology. A total of 6 077 samples recruited by Fudan University's Academy of Brain Artificial Intelligence Science and Technology were included, and the gut bacteria composition mainly shows the top 30 genera. Linear discriminant analysis Effect Size (LEfSe) was used to analyse the differences in gut bacteria. Pearson correlation coefficients were calculated to demonstrate the relationship of discrepant bacteria. CRC risk prediction models were used to rank the importance of valid discrepant bacteria.Results. Bacteroides, Eubacterium and Faecalibacterium were the top three bacteria in males with CRC, while Bacteroides, Subdoligranulum and Eubacterium were the top three bacteria in females with CRC. The abundance of gut bacteria (Escherichia, Eubacteriales, Clostridia, etc.) was higher in males with CRC compared with that in females with CRC. In addition, Dorea and Bacteroides were important CRC-related bacteria (P<0.001). Finally, the importance of discrepant bacteria was ranked based on CRC risk prediction models. Blautia, Barnesiella and Anaerostipes were the top three important discrepant bacteria between males with CRC and females with CRC. The value of AUC was 1.0, the sensitivity was 92.0 %, the specificity was 68.4 %, and the accuracy was 83.3 % in the discovery set.Conclusion. Gut bacteria were correlated with sexes and CRC. It is necessary to consider gender when gut bacteria are used to treat and predict CRC.

Effects of Hermetia illucens larvae meal on the Pacific white shrimp (Litopenaeus vannamei) revealed by innate immunity and 16S rRNA gene sequencing analysis

The larvae of the black soldier fly, Hermetia illucens, are now attracting attention and becoming promising sources for aquafeed ingredient due to the nutritious substance. However, the introduction of a novel ingredient into the recipe may have unpredictable effects on the innate immune function and gut bacteria composition of crustaceans. Therefore, the present study aimed to evaluate how dietary black soldier fly larvae meal (BSFLM) affected the antioxidant ability, innate immunity and gut microbiome of shrimp (Litopenaeus vannamei) fed with a practical diet, including the gene expression of Toll and immunodeficiency (IMD) pathways. Six experimental diets were formulated by replacing gradient levels of fish meal (0 %, 10 %, 20 %, 30 %, 40 % and 50 %) based on a commercial shrimp diet. Four replicates of shrimp were fed different diets three times daily for 60 days. Growth performance linearly decreased with increasing BSFLM inclusion. Results of antioxidative enzyme activities and gene expression suggested that low dietary BSFLM levels activated the antioxidant capacity of shrimp, while dietary BSFLM levels up to 100 g/kg may induce oxidative stress and inhibit glutathione peroxidase activity. Although traf6, toll1, dorsal and relish were significantly upregulated in different BSFLM groups, the expression of tak1 was significantly downregulated in groups containing BSFLM, implying the immune susceptibility may be weakened. Gut flora analysis indicated dietary BSFLM altered both beneficial and opportunistic pathogenic bacterial abundance, with low levels of dietary BSFLM increased the abundance of bacteria that may contribute to carbohydrate utilization, while high levels of dietary BSFLM may cause intestinal disease and low intestinal immune response. To conclude, 60–80 g/kg of dietary BSFLM showed no adverse effects on the growth, antioxidant capacity and gut flora of shrimp, which was the adequate level in shrimp diet. While 100 g/kg dietary BSFLM may induce oxidative stress and potentially weaken the innate immunity of shrimp.

Early environmental exposure to oxytetracycline in Danio rerio may contribute to neurobehavioral abnormalities in adult zebrafish

The common antibiotic oxytetracycline (OTC) is nowadays commonly found in natural aquatic environments. However, the underlying mechanisms of low-dose OTC exposure and its neurotoxic effects on aquatic animals remain unknown. In this study, we exposed zebrafish larvae to environmental concentrations of OTC in early life and performed neurobehavioral, 16S rRNA gene sequencing, and transcriptomic analyses. OTC exposure resulted in hyperactivity of larvae and a significant reduction in the number of neurons in the midbrain. The expression levels of 15 genes related to neural function changed. Additionally, the composition of 65 genera of the gut microbiota of larvae was altered, which may be one of the reasons for the abnormal neural development. We further studied the long-term outcomes among adult fish long after cessation of OTC exposure. OTC treatment caused adult fish to be depressive and impulsive, symbolizing bipolar disorder. Adult fish exposed to OTC had significantly fewer neurons and their gut bacteria composition did not recover 104 days after terminating OTC exposure. Finally, we analyzed the correlation between the gut microbiota of larvae, genes related to neural function, and metabolites of adult fish brain tissue. The results showed that the abundance of several members of the biome in larvae was related to the transcription levels of genes related to neural function, which were related to the metabolic levels in the adult brain. In conclusion, our study showed that early-life exposure to environmental concentrations of OTC can lead to persistent neurobehavioral abnormalities until adulthood through dysbiosis in the gut microbiota.

Adverse effects of titanium dioxide nanoparticles on beneficial gut bacteria and host health based on untargeted metabolomics analysis

Titanium dioxide (TiO2) is a common additive in foods, medicines, and personal care products. In recent years, nano-scale particles in TiO2 additives have been an increasing concern due to their potential adverse effects on human health, especially gut health. The objective of this study was to determine the impact of titanium dioxide nanoparticles (TiO2 NPs, 30 nm) on beneficial gut bacteria and host response from a metabolomics perspective. In the in vitro study, four bacterial strains, including Lactobacillus reuteri, Lactobacillus gasseri, Bifidobacterium animalis, and Bifidobacterium longum were subjected to the treatment of TiO2 NPs. The growth kinetics, cell viability, cell membrane permeability, and metabolomics response were determined. TiO2 NPs at the concentration of 200 μg/mL showed inhibitory effects on the growth of all four strains. The confocal microscope results indicated that the growth inhibitory effects could be associated with cell membrane damage caused by TiO2 NPs to the bacterial strains. Metabolomics analysis showed that TiO2 NPs caused alterations in multiple metabolic pathways of gut bacteria, such as tryptophan and arginine metabolism, which were demonstrated to play crucial roles in regulating gut and host health. In the in vivo study, mice were fed with TiO2 NPs (0.1 wt% in diet) for 8 weeks. Mouse urine was collected for metabolomics analysis and the tryptophan metabolism pathway was also significantly affected in TiO2 NPs-fed mice. Moreover, four neuroprotective metabolites were significantly reduced in both in vitro bacteria and in vivo urine samples. Overall, this study provides insights into the potential adverse effects of TiO2 NPs on gut bacteria and the metabolic responses of both bacteria and host. Further research is needed to understand the causality between gut bacteria composition and the metabolism pathway, which is critical to monitor the gut-microbiome mediated metabolome changes in toxicological assessment of food components.

Gut microbiota mediated the individualized efficacy of Temozolomide via immunomodulation in glioma

BackgroundTemozolomide (TMZ) is the preferred chemotherapy strategy for glioma therapy. As a second-generation alkylating agent, TMZ provides superior oral bio-availability. However, limited response rate (less than 50%) and high incidence of drug resistance seriously restricts TMZ’s application, there still lack of strategies to increase the chemotherapy sensitivity.MethodsLuci-GL261 glioma orthotopic xenograft model combined bioluminescence imaging was utilized to evaluate the anti-tumor effect of TMZ and differentiate TMZ sensitive (S)/non-sensitive (NS) individuals. Integrated microbiomics and metabolomics analysis was applied to disentangle the involvement of gut bacteria in TMZ sensitivity. Spearman’s correlation analysis was applied to test the association between fecal bacteria levels and pharmacodynamics indices. Antibiotics treatment combined TMZ treatment was used to confirm the involvement of gut microbiota in TMZ response. Flow cytometry analysis, ELISA and histopathology were used to explore the potential role of immunoregulation in gut microbiota mediated TMZ response.ResultsFirstly, gut bacteria composition was significantly altered during glioma development and TMZ treatment. Meanwhile, in vivo anti-cancer evaluation suggested a remarkable difference in chemotherapy efficacy after TMZ administration. Moreover, 16s rRNA gene sequencing and non-targeted metabolomics analysis revealed distinct different gut microbiota and immune infiltrating state between TMZ sensitive and non-sensitive mice, while abundance of differential gut bacteria and related metabolites was significantly correlated with TMZ pharmacodynamics indices. Further verification suggested that gut microbiota deletion by antibiotics treatment could accelerate glioma development, attenuate TMZ efficacy and inhibit immune cells (macrophage and CD8α+ T cell) recruitment.ConclusionsThe current study confirmed the involvement of gut microbiota in glioma development and individualized TMZ efficacy via immunomodulation, hence gut bacteria may serve as a predictive biomarker as well as a therapeutic target for clinical TMZ application.

Changes of intestinal microbiota in the giant salamander (Andrias davidianus) during growth based on high-throughput sequencing.

Despite an increasing appreciation of the importance of host-microbe interaction in healthy growth, information on gut microbiota changes of the Chinese giant salamander (Andrias davidianus) during growth is still lacking. Moreover, it is interesting to identify gut microbial structure for further monitoring A. davidianus health. This study explored the composition and functional characteristics of gut bacteria in different growth periods, including tadpole stage (ADT), gills internalization stage (ADG), 1 year age (ADY), 2 year age (ADE), and 3 year age (ADS), using high-throughput sequencing. The results showed that significant differences were observed in microbial community composition and abundance among different growth groups. The diversity and abundance of intestinal flora gradually reduced from larvae to adult stages. Overall, the gut microbial communities were mainly composed of Fusobacteriota, Firmicutes, Bacteroidota, and Proteobacteria. More specifically, the Cetobacterium genus was the most dominant, followed by Lactobacillus and Candidatus Amphibiichlamydia. Interestingly, Candidatus Amphibiichlamydia, a special species related to amphibian diseases, could be a promising indicator for healthy monitoring during A. davidianus growth. These results could be an important reference for future research on the relationship between the host and microbiota and also provide basic data for the artificial feeding of A. davidianus.

Orally administered Lactiplantibacillus plantarum OLL2712 decreased intestinal permeability, especially in the ileum: Ingested lactic acid bacteria alleviated obesity-induced inflammation by collaborating with gut microbiota.

Chronic inflammation caused by dietary obesity has been considered to induce lifestyle-related diseases and functional ingredients with anti-inflammatory effects are attracting attention. Although multiple studies on obesity had proved the anti-inflammatory effects of ingestion of lactic acid bacteria (LAB) and other functional ingredients on adipose tissue, the precise effects on the intestine, especially on the individual intestinal segments have not been made clear. In this study, we elucidated the mechanisms of Lactiplantibacillus plantarum (basonym: Lactobacillus plantarum) OLL2712 in suppressing obesity-induced inflammation using high fat diet (HFD)-fed mice obesity model. We orally administered heat-treated LAB to HFD-fed mice model, and investigated the inflammatory changes in adipose tissue and intestinal immune cells. We also analyzed gut microbiota, and evaluated the inflammation and permeability of the duodenum, jejunum, ileum and colon; four intestinal segments differing in gut bacteria composition and immune response. After 3-week LAB administration, the gene expression levels of proinflammatory cytokines were downregulated in adipose tissue, colon, and Peyer's patches (PP)-derived F4/80+ cells. The LAB treatment alleviated obesity-related gut microbiota imbalance. L. plantarum OLL2712 treatment helps maintain intestinal barrier function, especially in the ileum, possibly by preventing ZO-1 and Occludin downregulation. Our results suggest that the oral administration of the LAB strain regulated the gut microbiota, suppressed intestinal inflammation, and improved the gut barrier, which could inhibit the products of obesity-induced gut dysbiosis from translocating into the bloodstream and the adipose tissue, through which the LAB finally alleviated the inflammation caused by dietary obesity. Barrier improvement was observed, especially in the ileum, suggesting collaborative modulation of the intestinal immune responses by ingested LAB and microbiota.