Induced Gut Microbiota Research Articles

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.

Gut microbiota regulate wheat starch‐induced metabolic disorders via control of colonic SCD1

AbstractUnbalanced carbohydrate diets are linked to metabolic disorders; however, there is limited information on the role of gut microbiota. We explored differences in mice gut microbiota and metabolic phenotypes resulting from diets with different carbohydrate sources. To investigate the metabolic dysfunction and mechanism of the wheat flour and starch on metabolic disorders, we analyzed the changes of phenotype and biomarkers in rice and wheat flour diet in C57BL/6 mice (specific pathogen‐free) and fecal transplantation from antibiotic‐treated or germ‐free (GF) mice model. Rice‐fed mice presented normal metabolic reactions, whereas wheat‐fed mice exhibited increased body weight, insulin resistance, serum triglycerides, and fasting glucose levels. Wheat starch‐fed mice displayed lower fecal microbiota alpha diversity, with a reduced abundance of Bacteroidetes, than high‐fat diet (HFD)‐fed and chow‐fed mice. Fecal transplantation from antibiotic‐treated or GF mice revealed that metabolic disruption induced by wheat diet feeding was mediated through gut microbiota and stearoyl‐CoA desaturase 1 (SCD1) signaling in the colon. Taken together, wheat‐based diets induce gut microbiota alterations, causing obesity and metabolic diseases through molecular activity linked to colonic SCD1. Therefore, colonic SCD1 could be a therapeutic target for patients with metabolic diseases who consume high‐carbohydrate diets.

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.

Mitochondrial dysfunction-associated microbiota establishes a transmissible refractory response to anti-TNF therapy during ulcerative colitis

ABSTRACT Anti-TNF therapy can induce and maintain a remission status during intestinal bowel disease. However, up to 30% of patients do not respond to this therapy by mechanisms that are unknown. Here, we show that the absence of MCJ, a natural inhibitor of the respiratory chain Complex I, induces gut microbiota changes that are critical determinants of the lack of response in a murine model of DSS-induced inflammation. First, we found that MCJ expression is restricted to macrophages in human colonic tissue. Therefore, we demonstrate by transcriptomic analysis of colon macrophages from DSS-induced mice that MCJ-deficiency is linked to the expression of genes belonging to the FcγR signaling pathway and contains an anti-TNF refractory gene signature identified in ulcerative colitis patients. The gut microbial composition changes observed upon DSS treatment in the MCJ-deficient mice revealed the increased presence of specific colitogenic members, including Ruminococcus gnavus and Oscillospira, which could be associated with the non-response to TNF inhibitors. Further, we show that the presence of a microbiota associated resistance to treatment is dominant and transmissible to responsive individuals. Collectively, our findings underscore the critical role played by macrophage mitochondrial function in the gut ecological niche that can substantially affect not only the severity of inflammation but also the ability to successfully respond to current therapies.

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.

Combined oral intake of short and long fructans alters the gut microbiota in food allergy model mice and contributes to food allergy prevention

BackgroundIt has become clear that the intestinal microbiota plays a role in food allergies. The objective of this study was to assess the food allergy-preventive effects of combined intake of a short fructan (1-kestose [Kes]) and a long fructan (inulin ([Inu]) in an ovalbumin (OVA)-induced food allergy mouse model.ResultsOral administration of fructans lowered the allergenic symptom score and alleviated the decreases in rectal temperature and total IgA levels and increases in OVA-specific IgE and IgA levels induced by high-dose OVA challenge, and in particular, combined intake of Kes and Inu significantly suppressed the changes in all these parameters. The expression of the pro-inflammatory cytokine IL-4, which was increased in the allergy model group, was significantly suppressed by fructan administration, and the expression of the anti-inflammatory cytokine IL-10 was significantly increased upon Kes administration. 16 S rRNA amplicon sequencing of the gut microbiota and beta diversity analysis revealed that fructan administration may induce gut microbiota resistance to food allergy sensitization, rather than returning the gut microbiota to a non-sensitized state. The relative abundances of the genera Parabacteroides B 862,066 and Alloprevotella, which were significantly reduced by food allergy sensitization, were restored by fructan administration. In Parabacteroides, the relative abundances of Parabacteroides distasonis, Parabacteroides goldsteinii, and their fructan-degrading glycoside hydrolase family 32 gene copy numbers were increased upon Kes or Inu administration. The concentrations of short-chain fatty acids (acetate and propionate) and lactate were increased by fructan administration, especially significantly in the Kes + Inu, Kes, and Inu-fed (Inu, Kes + Inu) groups.ConclusionCombined intake of Kes and Inu suppressed allergy scores more effectively than single intake, suggesting that Kes and Inu have different allergy-preventive mechanisms. This indicates that the combined intake of these short and long fructans may have an allergy-preventive benefit.

Succinate signaling attenuates high-fat diet-induced metabolic disturbance and intestinal barrier dysfunction

Succinate is a vital signaling metabolite produced by the host and gut microbiota. Succinate has been shown to regulate host metabolic homeostasis and inhibit obesity-associated inflammation in macrophages by engaging its cognate receptor, SUCNR1. However, the contribution of the succinate-SUCNR1 axis to intestinal barrier dysfunction in obesity remains unclear. In the present study, we explored the effects of succinate-SUCNR1 signaling on high-fat diet (HFD)-induced intestinal barrier dysfunction. Using a SUCNR1-deficient mouse model under HFD feeding conditions, we identified the effects of succinate-SUCNR1 axis on obesity-associated intestinal barrier impairment. Our results showed that HFD administration decreased goblet cell numbers and mucus production, promoted intestinal pro-inflammatory responses, induced gut microbiota composition imbalance, increased intestinal permeability, and caused mucosal barrier dysfunction. Dietary succinate supplementation was sufficient to activate a type 2 immune response, trigger the differentiation of barrier-promoting goblet cells, suppress intestinal inflammation, restore HFD-induced mucosal barrier impairment and intestinal dysbiosis, and eventually exert anti-obesity effects. However, SUNNR1-deficient mice failed to improve the intestinal barrier function and metabolic phenotype in HFD mice. Our data indicate the protective role of the succinate-SUCNR1 axis in HFD-induced intestinal barrier dysfunction.

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.

Dietary fat source induces gut microbiota alterations and impacts chronic murine graft- versus-host disease severity

Abstract It has been observed that a constriction of the gut microbiome occurs with high fat diet, and likewise decreased microbiome diversity is directly correlated with more severe graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation. Taken together it is plausible that not only fat content, but source of dietary fat could influence gut microbiota and GvHD outcome. We sought to address this question and developed experimental rodent diets that have the same fat content (25% kcal fat, a moderate increase in fat content from normal chow) which differ only by fat source: animal- versus plant-derived fat and found that these diets drive alterations in gut microbiota diversity. Both diets yielded similar outcomes in an acute model of GvHD, however we found that mice fed the animal-derived fat diet exhibited worse survival and outcomes in a model of chronic GvHD, than mice fed the plant-derived fat diet. These findings correlated with increased inflammation and alterations in intestinal immune cell populations following chronic GvHD induction. Collectively, our data show that diets that are equal in macronutrient content but different in fat source can promote different gut microbiomes and in turn alter intestinal homeostasis and chronic GvHD outcome. Century for the Cure - Philanthropic Fund

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.

Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity.

Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anticancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation, which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues to promote optimal antitumor T cell responses in both the tumor-draining lymph nodes (TDLNs) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into mesenteric lymph nodes (MLNs) and TDLNs, diminished DC and effector CD8+ T cell responses, and attenuated responses to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anticancer immunity.

High dietary copper intake induces perturbations in the gut microbiota and affects host ovarian follicle development

Increasing evidence has shown that gut microbes play an important role in the reproductive endocrine system and the development of polycystic ovary syndrome (PCOS). However, whether environmental factors are involved in these gut microbiota alterations has seldom been studied. In this study, we aimed to explore the crucial role of an imbalanced gut microbiota on abnormal ovarian follicle development induced by Cu. A 1:1 matched case-control study with 181 PCOS patients and 181 controls was conducted using a propensity score matching protocol. Information regarding dietary Cu intake was obtained from a face-to-face dietary intake interview. Alterations in the gut microbiota were detected by high-throughput 16 S rDNA sequencing. The results showed that dietary Cu intake was positively correlated with the risk of PCOS, and the risk threshold was approximately 1.992 mg/d. Compared with those with dietary Cu intakes lower than 1.992 mg/d, those who had a higher dietary Cu intake had a 1.813-fold increased risk of PCOS (OR=1.813, 95% CI: 1.150–2.857). PCOS patients had a lower relative abundance of Bacteroides than controls (P = 0.003), and Bacteroides played a partial mediating role between dietary Cu exposure and PCOS (Pindirect effect=0.026, 95% CI: 0.002–0.072). In addition, an animal model of Cu exposure through the diet showed that Cu can induce gut microbiota disorder; increase serum levels of LPS, MDA, and IL-6; and alter host ovarian steroidogenesis to affect ovarian follicle development. Staphylococcus played a partial mediating role between Cu exposure and CYP17A1 (Pg_Staphylococcus=0.083, 95% CI: 0.001–0.228). Overall, this study shows that long-term exposure to high dietary Cu levels can affect the composition of the gut microbiota, cause inflammation and oxidative stress, and then interfere with hormone signaling, ultimately affecting ovarian follicle development.

Effect of edible bird's nest and N-acetylneuraminic acid on gut microbiota in different stages of pregnant rats fed with zinc deficient diet

Zinc deficiency diet during pregnancy and lactation have become an important hidden danger to the healthy development of offspring. Therefore, natural supplements are urgently needed to treat gut microbiota disorder induced by zinc deficiency diet. The study aims to investigate the effects of edible bird's nest (EBN) and N-acetylneuraminic acid (NANA) on gut microbiota in different stages of pregnant rats fed with zinc deficient diet. Zinc deficiency diet was used to induce gut microbiota disorder in pregnant rats. High-throughput 16S rRNA gene sequencing and bioinformatics analysis technology were also conducted. And the relationship between body weight, food intake and organ index of pregnant rats and differential microbiota was analyzed. It was found that dietary zinc deficiency can lead to gut microbiota disturbance in pregnant rats, which can be improved by EBN and NANA to increase beneficial bacteria such as Bacteroides, Bifidobacterium and Lactobacillus, and reduce the harmful ones such as Enterococcus, Turicibacter and Parabacteroides. These results can not only deepen the understanding of the effects of EBN and NANA on gut microbiota in pregnant rats, but also lay an important foundation for the further utilization of them in the pregnant population.

Dietary supplementation with casein/cyanidin-3-O-glucoside nanoparticles alters the gut microbiota in high-fat fed C57BL/6 mice

This study aims to investigate the dietary intervention effect of casein/cyanidin-3-O-glucoside nanoparticles (Cs-C3G) on high-fat-diet (HFD)induced gut microbiota disorders. In HFD-fed C57BL/6mice, Cs-C3G has ameliorated HFD-caused fat accumulation and liver oxidative stress. Cs-C3G as a dietary supplementation can restore the abundance and diversity of gut microbiota with descending the ratio of Firmicutes to Bacteroidetes, increasing some beneficial microorganisms, and reducing some opportunistic pathogenic bacteria. In general, Cs-C3G has a effect on regulating the disturbance of gut microbiota, and then prevents HFD-induced obesity and liver damage.

Fecal microbiota transplantation and short-chain fatty acids protected against cognitive dysfunction in a rat model of chronic cerebral hypoperfusion.

Clear roles and mechanisms in explaining gut microbial dysbiosis and microbial metabolites short-chain fatty acids (SCFAs) alterations in chronic cerebral ischemic pathogenesis have yet to be explored. In this study, we investigated chronic cerebral hypoperfusion (CCH)-induced gut microbiota and metabolic profiles of SCFAs as well as the effects and mechanisms of fecal microbiota transplantation (FMT) and SCFAs treatment on CCH-induced hippocampal neuronal injury. Bilateral common carotid artery occlusion (BCCAo) was used to establish the CCH model. Gut microbiota and SCFAs profiles in feces and hippocampus were evaluated by 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. RNA sequencing analysis was performed in hippocampal tissues. The potential molecular pathways and differential genes were verified through western blot, immunoprecipitation, immunofluorescence, and ELISA. Cognitive function was assessed via the Morris water maze test. Ultrastructures of mitochondria and synapses were tested through a transmission electron microscope. Chronic cerebral hypoperfusion induced decreased fecal acetic and propionic acid and reduced hippocampal acetic acid, which were reversed after FMT and SCFAs administration by changing fecal microbial community structure and compositions. Furthermore, in the hippocampus, FMT and SCFAs replenishment exerted anti-neuroinflammatory effects through inhibiting microglial and astrocytic activation as well as switching microglial phenotype from M1 toward M2. Moreover, FMT and SCFAs treatment alleviated neuronal loss and microglia-mediated synaptic loss and maintained the normal process of synaptic vesicle fusion and release, resulting in the improvement of synaptic plasticity. In addition, FMT and SCFAs supplement prevented oxidative phosphorylation dysfunction via mitochondrial metabolic reprogramming. The above effects of FMT and SCFAs treatment led to the inhibition of CCH-induced cognitive impairment. Our findings highlight FMT and SCFAs replenishment would be the feasible gut microbiota-based strategy to mitigate chronic cerebral ischemia-induced neuronal injury.

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.

Antibiotics induced gut microbiota disbiosis rescues the behavioral phenotype in a maternal immune-activation (MIA) model of autism spectrum disorder / schizophrenia

Evolution has long been considered to be a conservative process in which new genes arise from pre-existing genes through gene duplication, domain shuffling, horizontal transfer, overprinting, retrotransposition, etc. However, this view is changing as new genes originating from non-genic sequences are discovered in different organisms. Still, rather limited functional information is available. Here, we have identified TWISTED1 (TWT1), a possible de novo-originated protein-coding gene that modifies microtubule arrangement and causes helicoidal growth in Arabidopsis thaliana when its expression is increased. Interestingly, even though TWT1 is a likely recent gene, the lack of TWT1 function affects A. thaliana development. TWT1 seems to have originated from a non-genic sequence. If so, it would be one of the few examples to date of how during evolution de novo genes are integrated into developmental cellular and organismal processes.