Induced Gut Microbiota Dysbiosis Research Articles

Antibiotic Cocktail Effects on Intestinal Microbial Community, Barrier Function, and Immune Function in Early Broiler Chickens.

This study investigated the effects of an antibiotic cocktail on intestinal microbial composition, mechanical barrier structure, and immune functions in early broilers. One-day-old healthy male broiler chicks were treated with a broad-spectrum antibiotic cocktail (ABX; neomycin, ampicillin, metronidazole, vancomycin, and kanamycin, 0.5 g/L each) or not in drinking water for 7 and 14 days, respectively. Sequencing of 16S rRNA revealed that ABX treatment significantly reduced relative Firmicutes, unclassified Lachnospiraceae, unclassified Oscillospiraceae, Ruminococcus torques, and unclassified Ruminococcaceae abundance in the cecum and relative Firmicutes, Lactobacillus and Baccillus abundance in the ileum, but significantly increased richness (Chao and ACE indices) and relative Enterococcus abundance in the ileum and cecum along with relatively enriched Bacteroidetes, Proteobacteria, Cyanobacteria, and Enterococcus levels in the ileum following ABX treatment for 14 days. ABX treatment for 14 days also significantly decreased intestinal weight and length, along with villus height (VH) and crypt depth (CD) of the small intestine, and remarkably increased serum LPS, TNF-α, IFN-γ, and IgG levels, as well as intestinal mucosa DAO and MPO activity. Moreover, prolonged use of ABX significantly downregulated occludin, ZO-1, and mucin 2 gene expression, along with goblet cell numbers in the ileum. Additionally, chickens given ABX for 14 days had lower acetic acid, butyric acid, and isobutyric acid content in the cecum than the chickens treated with ABX for 7 days and untreated chickens. Spearman correlation analysis found that those decreased potential beneficial bacteria were positively correlated with gut health-related indices, while those increased potential pathogenic strains were positively correlated with gut inflammation and gut injury-related parameters. Taken together, prolonged ABX application increased antibiotic-resistant species abundance, induced gut microbiota dysbiosis, delayed intestinal morphological development, disrupted intestinal barrier function, and perturbed immune response in early chickens. This study provides a reliable lower-bacteria chicken model for further investigation of the function of certain beneficial bacteria in the gut by fecal microbiota transplantation into germ-free or antibiotic-treated chickens.

Long-term Bisphenol S exposure induced gut microbiota dysbiosis, obesity, hepatic lipid accumulation, intestinal lesions and dyslipidemia in mice

Bisphenol S (BPS) is a commonly detected chemical raw material in water, which poses significant threats to both the ecological environment and human health. Despite being recognized as a typical endocrine disruptor and a substitute for Bisphenol A, the toxicological effects of BPS remain nonnegligible. In order to comprehensively understand the health impacts of BPS, a long-term (154 days) exposure experiment was conducted on mice, during which the physiological indicators of the liver, intestine, and blood were observed. The findings revealed that exposure to BPS resulted in dysbiosis of the gut microbiota, obesity, hepatic lipid accumulation, intestinal lesions, and dyslipidemia. Furthermore, there exists a significant correlation between gut microbiota and indicators of host health. Consequently, the identification of specific gut microbiota can be considered as potential biomarkers for the evaluation of risk associated with BPS. This study will effectively address the deficiency in toxicological data pertaining to BPS. The novel BPS data obtained from this research can serve as a valuable reference for professionals in the field.

In situ profiling reveals spatially metabolic injury in the initiation of polystyrene nanoplastic-derived intestinal epithelial injury in mice

Despite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury.

Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood–brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

Polyethylene microplastics induced gut microbiota dysbiosis leading to liver injury via the TLR2/NF-κB/NLRP3 pathway in mice

Microplastics (MPs) are ubiquitous environmental contaminants that have negative impacts on health and safety. The gut microbiota plays multiple roles as a newly discovered virtual metabolic organ. The objective of this study was to investigate the potential of MPs to cause liver injury by disrupting the balance of gut microbiota. The results indicated that exposure to MPs resulted in liver damage and disrupted the homeostasis of gut microbiota. MPs significantly reduced the liver organ coefficient, leading to liver cell injury and impaired function. Additionally, there was an increase in the expression of fibril-related proteins, which positively correlated with MPs concentration. Furthermore, MPs increased the relative abundances of Desulfovibrio, Clostridia, Enterorhabdus, Bacteroides, and Gemella while decreasing the abundance of Dubosoella. Different concentrations of MPs exhibited varying effects on specific bacterial groups, however, both concentrations resulted in an increase in pathogenic bacteria and a decrease in beneficial bacteria, as well as alterations in microbial structure. Moreover, MPs induced oxidative stress, inflammation, apoptosis and necrosis in liver cells. The study found that MPs disrupted gut microbiota homeostasis and activated TLR2/NF-κB/NLRP3 pathway in the liver, providing a new insight into the mechanism underlying MPs-induced liver injury. These findings serve as a warning regarding environmental pollution caused by MPs.

Per- and polyfluoroalkyl substance (PFAS) mixtures induce gut microbiota dysbiosis and metabolic disruption in silkworm (Bombyx mori L.)

Mixed legacy and emerging per- and polyfluoroalkyl substances (PFASs) are commonly found in soil and dust; however, the potential toxicity of PFAS mixtures (mPFASs) in insects is unknown. Using 16S rRNA gene sequencing and transcriptome sequencing (RNA-Seq), we evaluated the adverse effects of mPFASs on silkworms, a typical lepidopteran insect. After exposure to mPFASs, the silkworm midgut was enriched with high levels of PFASs, which induced histopathological changes. The composition of the midgut microbiota was significantly affected by mPFAS exposure, and functional predictions revealed significant disruption of some metabolic pathways. RNA-seq analysis revealed that mPFASs significantly changed the transcription profiles. Functional enrichment analysis of the differentially expressed genes also revealed that biological processes related to metabolic pathways and the digestive system were significantly affected, similar to the results of the gut microbiota analysis, suggesting that mPFAS exposure had an adverse effect on the metabolic function of silkworms and may further affect their normal growth. Finally, the significant correlation between abundance changes in the gut microbiota and metabolism/digestion-related genes further highlighted the role of the gut microbiota in mPFAS-related processes affecting the metabolic functions of silkworms. To our knowledge, this study is the first to evaluate the toxic effects of mPFASs in insects and provide basic data for further PFAS toxicity investigations in insects and comprehensive ecological risk assessments of mPFASs.

CHRONIC HIGH-FAT DIET CONSUMPTION ACCELERATES OSTEOBLAST DYSFUNCTION AND OSTEOPOROSIS BY GUT MICROBIAL METABOLITE TRIMETHYLAMINE-N-OXIDE

Obesity is correlated with the development of osteoporotic diseases. Gut microbiota-derived metabolite trimethylamine-n-oxide (TMAO) accelerates obesity-mediated tissue deterioration. This study was aimed to investigate what role TMAO may play in osteoporosis development during obesity.Mice were fed with high-fat diet (HFD; 60 kcal% fat) or chow diet (CD; 10 kcal% fat) or 0.2% TMAO in drinking water for 6 months. Body adiposis and bone microstructure were investigated using μCT imaging. Gut microbiome and serum metabolome were characterized using 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry. Osteogenic differentiation of bone-marrow mesenchymal cells was quantified using RT-PCR and von Kossa staining. Cellular senescence was evaluated by key senescence markers p16, p21, p53, and senescence association β-galactosidase staining.HFD-fed mice developed hyperglycemia, body adiposis and osteoporosis signs, including low bone mineral density, sparse trabecular microarchitecture, and decreased biomechanical strength. HFD consumption induced gut microbiota dysbiosis, which revealed a high Firmicutes/Bacteroidetes ratio and decreased α-diversity and abundances of beneficial microorganisms Akkermansiaceae, Lactobacillaceae, and Bifidobacteriaceae. Serum metabolome uncovered increased serum L-carnitine and TMAO levels in HFD-fed mice. Of note, transplantation of fecal microbiota from CD-fed mice compromised HFD consumption-induced TMAO overproduction and attenuated loss in bone mass, trabecular microstructure, and bone formation rate. TMAO treatment inhibited trabecular and cortical bone mass and biomechanical characteristics; and repressed osteogenic differentiation capacity of bone-marrow mesenchymal cells. Mechanistically, TMAO accelerated mitochondrial dysfunction and senescence program, interrupted mineralized matrix production in osteoblasts.Gut microbial metabolite TMAO induced osteoblast dysfunction, accelerating the development of obesity-induced skeletal deterioration. This study, for the first time, conveys a productive insight into the catabolic role of gut microflora metabolite TMAO in regulating osteoblast activity and bone tissue integrity during obesity.

Microbiota-mediated metabolic perturbations in the gut and brain of mice after microplastic exposure

Microplastics (MPs), emerging environmental toxicants, have drawn attention because of their wide distribution in the environment. Exposure to MPs induces gut microbiota dysbiosis, intestinal barrier dysfunction, metabolic perturbations, and neurotoxicity in different rodents. However, the relationship between MPs, gut microbiota, and the metabolome of the gut and brain in mice remains unclear. In this study, female C57BL/6 mice were orally gavaged with vehicle, 200 nm MP, and 800 nm MP three times per week for four weeks. Cecal contents were collected for gut microbiota analysis using 16S rRNA gene sequencing. Intestinal and brain tissues from mice were used to determine metabolic profiles using liquid chromatography-mass spectrometry (LC-MS). The results showed that MP altered microbiota composition, accompanied by metabolic perturbations in the mouse gut and brain. Specifically, Firmicutes and Bacteroidetes were suggested to be important phyla for MP exposure, partially dominating further metabolite alterations. Simultaneously, MP-induced metabolic profiles were associated with energy homeostasis and bile acid, nucleotide, and carnitine metabolic pathways. The results of the mediation analysis further revealed an MP-microbiota-metabolite relationship. Our results indicate that MPs can induce gut dysbiosis and disturb metabolic dysfunction in the mouse brain and/or intestine. Integrative omics approaches have the potential to monitor MP-induced molecular responses in various organs and systematically elucidate the complex mechanisms of human health effects.

Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis

Apolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction–associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulatory effect of APOH, mediated through various pathways, on metabolic homeostasis and MASLD pathogenesis. We analyzed serum marker levels, liver histopathology, and cholesterol metabolism–related gene expression in global ApoH−/− C57BL/6 male mice. We used RNA sequencing and metabolomic techniques to investigate the association between liver metabolism and bacterial composition. Fifty-two differentially expressed genes were identified between ApoH−/− and WT mice. The mRNA levels of de novo lipogenesis genes were highly upregulated in ApoH−/− mice than in WT mice. Fatty acid, glycerophospholipid, sterol lipid, and triglyceride levels were elevated, while hyodeoxycholic acid levels were significantly reduced in the liver tissues of ApoH−/− mice than in those of WT mice. Microbial beta diversity was lower in ApoH−/− mice than in WT mice, and gut microbiota metabolic functions were activated in ApoH−/− mice. Moreover, ApoH transcripts were downregulated in patients with MASLD, and APOH-related differential genes were enriched in lipid metabolism. Open-source transcript-level data from human metabolic dysfunction–associated steatohepatitis livers reinforced a significant association between metabolic dysfunction–associated steatohepatitis and APOH downregulation. In conclusion, our studies demonstrated that APOH downregulation aggravates fatty liver and induces gut microbiota dysbiosis by dysregulating bile acids. Our findings offer a novel perspective on APOH-mediated lipid metabolic dysbiosis and provide a valuable framework for deciphering the role of APOH in fatty liver disease.

Continuous oral exposure to micro- and nanoplastics induced gut microbiota dysbiosis, intestinal barrier and immune dysfunction in adult mice

Micro/nanoplastics in the environment can be ingested by organisms and spread throughout the food chain, ultimately posing a threat to human health. However, the risk of continuous oral exposure in mammals remains unresolved. In this study, we utilized a continuous gavage mouse model to investigate the potential intestinal risks associated with oral exposure to polystyrene micro/nanoplastics (PS-MNPs) with environmentally relevant concentrations. The effects of PS-MNPs with different particle sizes on the gut microbiota, intestinal barrier, and intestinal immune function were evaluated. PS-MNPs can accumulate in the intestine after oral exposure and alter the composition of the gut microbiota. Exposure to PS-MNPs significantly reduced the ratio of Firmicutes to Bacteroidetes as well as the number of potentially beneficial bacteria in the gut, while the number of potentially harmful bacteria significantly increased. The short-chain fatty acids metabolized by gut microbiota were significantly changed by PS-MNPs. Exposure to PS-MNPs disrupts the function of the intestinal barrier and leads to inflammation in the intestines. The levels of secretory immunoglobulin A in the intestine and the differentiation of CD4+ and CD8+ T cells in mesenteric lymph nodes were significantly decreased by PS-MNPs. Moreover, the impact of PS-MNPs on mammalian intestinal health is influenced by the exposure duration and particle size, rather than the concentration. It also suggests that nanoplastics may pose more severe environmental risks.

An obesogenic diet increases atherosclerosis through promoting microbiota dysbiosis-induced gut lymphocyte trafficking into the periphery

Although high-fat diet (HFD)-induced gut microbiota dysbiosis is known to affect atherosclerosis, the underlying mechanisms remain to be fully explored. Here, we show that the progression of atherosclerosis depends on a gut microbiota shaped by an HFD but not a high-cholesterol (HC) diet and, more particularly, on low fiber (LF) intake. Mechanistically, gut lymphoid cells impacted by HFD- or LF-induced microbiota dysbiosis highly proliferate in mesenteric lymph nodes (MLNs) and migrate from MLNs to the periphery, which fuels Tcell accumulation within atherosclerotic plaques. This is associated with the induction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) within plaques and the presence of enterotropic lymphocytes expressing β7 integrin. MLN resection or lymphocyte deficiency abrogates the pro-atherogenic effects of a microbiota shaped by LF. Our study shows a pathological link between a diet-shaped microbiota, gut immune cells, and atherosclerosis, suggesting that a diet-modulated microbiome might be a suitable therapeutic target to prevent atherosclerosis.

Dextran sulfate sodium-induced gut microbiota dysbiosis aggravates liver injury in mice with S100-induced autoimmune hepatitis

Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation.

Environmental cadmium exposure facilitates mammary tumorigenesis via reprogramming gut microbiota-mediated glutamine metabolism in MMTV-Erbb2 mice

Cadmium (Cd) is a heavy metal that has been widely reported to be linked to the onset and progression of breast cancer (BC). However, the mechanism of Cd-induced mammary tumorigenesis remains elusive. In our study, a transgenic mouse model that spontaneously develops tumors through overexpression of wild-type Erbb2 (MMTV-Erbb2) was constructed to investigate the effects of Cd exposure on BC tumorigenesis. The results showed that oral exposure to 3.6 mg/L Cd for 23 weeks dramatically accelerated tumor appearance and growth, increased Ki67 density and enhanced focal necrosis and neovascularization in the tumor tissue of MMTV-Erbb2 mice. Notably, Cd exposure enhanced glutamine (Gln) metabolism in tumor tissue, and 6-diazo-5-oxo-l-norleucine (DON), a Gln metabolism antagonist, inhibited Cd-induced breast carcinogenesis. Then our metagenomic sequencing and mass spectrometry-based metabolomics confirmed that Cd exposure disturbed gut microbiota homeostasis, especially Helicobacter and Campylobacter abundance remodeling, which altered the gut metabolic homeostasis of Gln. Moreover, intratumoral Gln metabolism profoundly increased under Cd-elevated gut permeability. Importantly, depletion of microbiota with an antibiotic cocktail (AbX) treatment led to a significant delay in the appearance of palpable tumors, inhibition of tumor growth, decrease in tumor weight, reduction in Ki67 expression and low-grade pathology in Cd-exposed MMTV-Erbb2 mice. Also, transplantation of Cd-modulated microbiota decreased tumor latency, accelerated tumor growth, increased tumor weight, upregulated Ki67 expression and exacerbated neovascularization as well as focal necrosis in MMTV-Erbb2 mice. In summary, Cd exposure induced gut microbiota dysbiosis, elevated gut permeability and increased intratumoral Gln metabolism, leading to the promotion of mammary tumorigenesis. This study provides novel insights into environmental Cd exposure-mediated carcinogenesis.

Hyperammonemia induced gut microbiota dysbiosis and motor coordination disturbances in mice: new insight into gut‑brain axis involvement in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric hepatic‑induced syndrome in which several factors are involved in promoting brain perturbations, with ammonia being the primary factor. Motor impairment, incoordination, and gut dysbiosis are some of the well‑known symptoms of HE. Nevertheless, the link between the direct effect of hyperammonemia and associated gut dysbiosis in the pathogenesis of HE is not well established. Thus, this work aimed to assess motor function in hyperammonemia and gut dysbiosis in mice. Twenty‑eight Swiss mice were distributed into three groups: two‑week and four‑week hyperammonemia groups were fed with an ammonia‑rich diet (20% w/w), and the control group was pair‑fed with a standard diet. Motor performance in the three groups was measured through a battery of motor tests, namely the rotarod, parallel bars, beam walk, and static bars. Microbial analysis was then carried out on the intestine of the studied mice. The result showed motor impairments in both hyperammonemia groups. Qualitative and quantitative microbiological analysis revealed decreased bacterial load, diversity, and ratios of both aerobic and facultative anaerobic bacteria, following two and four weeks of ammonia supplementation. Moreover, the Shannon diversity index revealed a time‑dependent cutback of gut bacterial diversity in a treatment‑time‑dependent manner, with the presence of only Enterobacteriaceae, Streptococcaceae, and Enterococcaceaeat at four weeks. The data showed that ammonia‑induced motor coordination deficits may develop through direct and indirect pathways acting on the gut‑brain axis.

Aflatoxin B1 induces liver injury by disturbing gut microbiota-bile acid-FXR axis in mice.

Aflatoxin B1 (AFB1) is one of major pollutant in food and feed worldwide. The purpose of this study is to investigate the mechanism of AFB1-induced liver injury. Our results showed that AFB1 caused hepatic bile duct proliferation, oxidative stress, inflammation and liver injury in mice. AFB1 exposure induced gut microbiota dysbiosis and reduced fecal bile salt hydrolase (BSH) activity. AFB1 exposure promoted hepatic bile acid (BA) synthesis and changed intestinal BA metabolism, especially increased intestinal conjugated bile acids levels. AFB1 exposure inhibited intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) signaling. Furthermore, the mice received fecal microbiota transplantation from AFB1-treated mice induced liver injury, reduced intestinal FXR signaling and increased hepatic BA synthesis. Finally, the intestine-restricted FXR agonist treatment decreased hepatic BA synthesis, ROS level, inflammation and liver injury in AFB1-treated mice. This study suggests that modifying the gut microbiota, altering intestinal BA metabolism and/or activating intestinal FXR/FGF-15 signaling may be of value for the treatment of AFB1-induced liver disease.

Gut-derived bacterial LPS attenuates incubation of methamphetamine craving via modulating microglia

BackgroundThe microbiota-gut-brain axis plays a critical role in the pathophysiology of neuropsychiatric disorders, and the compositions of gut microbiota are altered by addictive drugs. However, the role of gut microbiota in the incubation of methamphetamine (METH) craving remains poorly understood. Methods16S rRNA gene sequencing was performed to assess the richness and diversity of gut microbiota in METH self-administration model. Hematoxylin and eosin staining was performed to evaluate the integrity of intestinal barrier. Immunofluorescence and three-dimensional reconstruction were performed to assess the morphologic changes of microglia. Serum levels of lipopolysaccharide (LPS) were determined using the rat enzyme-linked immunosorbent assay kits. Quantitative real-time PCR was performed to assess transcript levels of dopamine receptor, glutamate ionotropic AMPA receptor 3 and brain-derived neurotrophic factor. ResultsMETH self-administration induced gut microbiota dysbiosis, intestinal barrier damage and microglia activation in the nucleus accumbens core (NAcc), which was partially recovered after prolonged withdrawal. Microbiota depletion via antibiotic treatment increased LPS levels and induced a marked change in the microglial morphology in the NAcc, as indicated by the decreases in the lengths and numbers of microglial branches. Depleting the gut microbiota also prevented the incubation of METH craving and increased the population of Klebsiella oxytoca. Furthermore, Klebsiella oxytoca treatment or exogenous administration of the gram-negative bacterial cell wall component LPS increased serum and central LPS levels, induced microglial morphological changes and reduced the dopamine receptor transcription in the NAcc. Both treatments and NAcc microinjections of gut-derived bacterial LPS significantly decreased METH craving after prolonged withdrawal. ConclusionsThese data suggest that LPS from gut gram-negative bacteria may enter circulating blood, activate microglia in the brain and consequently decrease METH craving after withdrawal, which may have important implications for novel strategies to prevent METH addiction and relapse.

Effects of hazelnut protein isolate-induced food allergy on the gut microenvironment in a BALB/c mouse model.

Hazelnuts are reported as among the nuts that cause severe allergic reactions. However, few systematic studies exist on the changes in the gut microenvironment following hazelnut allergy. This study focused on the effects of hazelnut allergy on the duodenum, jejunum, ileum and colon microenvironment in vivo. We established a hazelnut protein isolate (HPI)-allergic mouse model, which was distinguished by the visible allergy symptoms, dropped temperatures and enhanced allergic inflammatory factor levels in serum, such as HPI-specific immunoglobulin E (sIgE), sIgG2a, interleukin-4, histamine, mouse mast cell protease-1, TNF-α, monocyte chemotactic protein-1 and lipopolysaccharide. For HPI sensitized mice, aggravated mast cell degranulation, severe morphologic damage and inflammatory cell infiltration were observed in the duodenum, jejunum, ileum, and colon, while goblet cell numbers were reduced in the duodenum, jejunum and ileum. Secretory IgA of the jejunum and tight junctions of the duodenum and jejunum were decreased significantly after HPI sensitization. There was no remarkable difference in the pH values of small intestinal contents, but the pH values of colonic contents were elevated, which was due to the decreased short-chain fatty acids (mainly acetate, propionate and butyrate) in the colon. The antioxidant capacity of both large and small intestinal contents declined after HPI sensitization, as evidenced by the increased malondialdehyde and decreased superoxide dismutase activity. HPI sensitization induced gut microbiota dysbiosis with decreased α diversity and altered β diversity in colonic contents. Spearman correlation analysis indicated that the increased characteristic genera, namely Bacteroides, Lactobacillus, Alloprevotella, Erysipelatoclostridium, Parabacteroides, and Helicobacter, played potentially synergistic roles in promoting allergy and gut microenvironment dysregulation.

Alterations of the fecal microbiota in relation to acute COVID-19 infection and recovery

People with acute COVID-19 due to SARS-CoV-2 infection experience a range of symptoms, but major factors contributing to severe clinical outcomes remain to be understood. Emerging evidence suggests associations between the gut microbiome and the severity and progression of COVID-19. To better understand the host-microbiota interactions in acute COVID-19, we characterized the intestinal microbiome of patients with active SARS-CoV-2 infection in comparison to recovered patients and uninfected healthy controls. We performed 16S rRNA sequencing of stool samples collected between May 2020 and January 2021 from 20 COVID-19-positive patients, 20 COVID-19-recovered subjects and 20 healthy controls. COVID-19-positive patients had altered microbiome community characteristics compared to the recovered and control subjects, as assessed by both α- and β-diversity differences. In COVID-19-positive patients, we observed depletion of Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae, as well as decreased relative abundances of the genera Faecalibacterium, Adlercreutzia, and the Eubacterium brachy group. The enrichment of Prevotellaceae with COVID-19 infection continued after viral clearance; antibiotic use induced further gut microbiota perturbations in COVID-19-positive patients. In conclusion, we present evidence that acute COVID-19 induces gut microbiota dysbiosis with depletion of particular populations of commensal bacteria, a phenomenon heightened by antibiotic exposure, but the general effects do not persist post-recovery.

Correlations between gastrointestinal and oral microbiota in children with cerebral palsy and epilepsy.

We here studied the correlation between gut and oral microbiota in children with cerebral palsy and Epilepsy (CPE). We enrolled 27 children with this condition from the social welfare center of Longgang District, collected their oral plaque and stool samples, and analyzed their gut microbiota (GM) and oral microbiota (OM) through 16S rRNA gene sequencing. Taxonomical annotation revealed that the levels of Firmicutes and Bacteroides in the oral cavity were significantly lower in CPE children than in healthy children, whereas the abundance of Actinomycetes increased significantly in CPE children. In addition, Prevotella, Fusobacterium, and Neisseria were the top three abundant genera, representing 15.49%, 9.34%, and 7.68% of the OM and suggesting potential correlations with caries, periodontitis, and malnutrition. For the GM, Bifidobacterium, Bacteroides, and Prevotella were the top three abundant genera in CPE children and probably contributed to the development of chronic inflammation and malnutrition. Furthermore, the OM and GM correlated with each other closely, and the bacterial components of these microbiota in CPE children were remarkably different from those in healthy children, such as Bifidobacterium, Fusobacterium, Bacteroides, and Neisseria. Conclusively, dysbiotic OM can translocate to the intestinal tract and induce GM dysbiosis, suggesting the consistency between OM and GM variations. Altered oral and gut microbial structures have potential impacts on the occurrence of clinical diseases such as periodontitis, caries, and malnutrition.

Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer’s disease

BackgroundAlzheimer's disease (AD) is the most common neurodegenerative disease and its pathogenesis is still unclear. There is dysbiosis of gut microbiota in AD patients. More importantly, dysbiosis of the gut microbiota has been observed not only in AD patients, but also in patients with mild cognitive impairment (MCI). However, the mechanism of gut microbiota dysbiosis in AD is poorly understood. Cholinergic anti-inflammatory pathway is an important pathway for the central nervous system (CNS) regulation of peripheral immune homeostasis, especially in the gut. Therefore, we speculated that dysfunction of cholinergic anti-inflammatory pathway is a potential pathway for dysbiosis of the gut microbiota in AD.MethodsIn this study, we constructed AD model mice by injecting Aβ1–42 into the lateral ventricle, and detected the cognitive level of mice by the Morris water maze test. In addition, 16S rDNA high-throughput analysis was used to detect the gut microbiota abundance of each group at baseline, 2 weeks and 4 weeks after surgery. Furthermore, immunofluorescence and western blot were used to detect alteration of intestinal structure of mice, cholinergic anti-inflammatory pathway, and APP process of brain and colon in each group.ResultsAβ1–42 i.c.v induced cognitive impairment and neuron damage in the brain of mice. At the same time, Aβ1–42 i.c.v induced alteration of gut microbiota at 4 weeks after surgery, while there was no difference at the baseline and 2 weeks after surgery. In addition, changes in colon structure and increased levels of pro-inflammatory factors were detected in Aβ1–42 treatment group, accompanied by inhibition of cholinergic anti-inflammatory pathways. Amyloidogenic pathways in both the brain and colon were accelerated in Aβ1–42 treatment group.ConclusionsThe present findings suggested that Aβ in the CNS can induce gut microbiota dysbiosis, alter intestinal structure and accelerate the amyloidogenic pathways, which were related to inhibiting cholinergic anti-inflammatory pathways.