Perturbation Of Gut Microbiota Research Articles

Gut microbiome perturbations influence brain amyloidosis only in the presence of microglia in APPPS1‐21 mice

AbstractBackgroundIn prior efforts, we demonstrated reduced amyloidosis and altered microgliosis in long‐term antibiotics (abx)‐treated APPPS1‐21 male mice. Restoration of the gut microbiome into abx‐treated male mice by fecal microbiota transfer (FMT) established a causality between the gut microbiome and amyloidosis. We have used FMT studies using our current short‐term abx APPPS1‐21 mice to evaluate the microbiome‐microglia‐amyloidosis axis.MethodShort‐term, postnatal abx (4mg/ml Kanamycin, 0.35mg/ml Gentamicin, 8500U/ml Colistin, 2.15mg/ml Metronidazole, 0.45mg/ml Vancomycin: post‐natal day 14 to day 21) was performed. To establish causality, we performed FMT (200µl of 5mg/ml fecal slurry daily gavage) into abx‐treated APPPS1‐21 male mice. Pathogenicity of the gut microbiome in WT or Tg mice were confirmed using age‐matched FMT from WT and Tg controls into abx‐treated male mice. We performed total RNAseq transcriptome analysis to evaluate potential mechanism(s). The role of microglial cells were evaluated in PLX6522 (CSF‐1 receptor inhibitor)‐treated FMT‐transplanted abx‐treated APPPS1‐21 male mice. Nine weeks old GF APPPS1‐21 were used to characterize the amyloidosis and glial cells in both genders.ResultAn early life abx treatment resulted in gut microbiota changes in a sex‐dependent manner. Only male mice showed reduced amyloidosis and altered microglial phenotypes. Age matched Tg FMT or WT FMT resulted in higher amyloidosis in abx‐treated male mice. RNAseq analysis of total cortical RNA showed significantly different mRNA levels that occurred in a sex‐specific manner and changes in abx‐treated male mice were restored with FMT. GO term analysis showed gliogenesis and microglia development as significantly altered pathways in abx‐treated male group only. To confirm the exact role of the microglia in this model, we employed PLX6522 in FMT‐treated ABX‐male mice. Microglia depletion did not result in an FMT‐dependent increase in amyloidosis in abx‐treated male mice. Finally, germ‐free APPPS1‐21 mice showed reduced amyloidosis that occurs in a sex‐specific manner.ConclusionFrom GF APPPS1‐21 and FMT‐treated abx‐male APPPS1‐21 studies, we conclude that gut microbiome plays a critical role in modulating amyloidosis in APPPS1‐21 mice. Furthermore, microglia mediates the effects of early life gut microbiota perturbations, which results in altered amyloidosis in APPPS1‐21 male mice.

Antibiotic Perturbation of Gut Microbiota Alters Osseointegration Around an Intramedullary Nail in Mice With or Without Osteomyelitis

Treatment of osteomyelitis requires prolonged antibiotic therapy which significantly alters the gut microbiota. While the influences on bone mass and microstructure have been extensively studied, it is poorly understood what impact the changes in gut microbiota may have on the host response to osseointegration around an intramedullary nail implanted. Here, we explored the influence of gut microbiota on the bone osseointegration process around an implant under two conditions: implantation of an intramedullary nail in the bone marrow cavity and chronic osteomyelitis(CO) induced by Staphylococcus aureus infection. Body weight, hepatorenal functions, serum levels of proinflammatory cytokines were monitored. The composition of gut microbiota was assessed via 16S rRNA sequencing, and the bone condition was analyzed via micro-computed tomography and hematoxylin and eosin staining, safranin O-fast green and Goldner's trichrome. Osteoblastogenesis and osteoclastogenesis were assessed by detecting tartrate-resistant acid phosphatase and osterix expression. We found that perturbation of gut microbiota led to delayed osseointegration and increased levels of proinflammatory cytokines in the serum (p<0.05), lower bone mass (p<0.05), deficient endochondral ossification and bone formation, reduced osteoblastogenesis (p<0.05) and enhanced osteoclastogenesis (p<0.001). Survival rates (p=0.002) and bacterial loads (p=0.0363) in bone differed significantly between the CO and antibiotic-treated CO mice, but cytokines levels, bone mineral density, and bone formation did not differ, likely because of the severely damaged bone structure. In summary, antibiotic treatment perturbed the gut microbiota and significantly interfered with the bone osseointegration around the nail by increasing proinflammatory cytokine levels in circulation, inhibiting osteoblastogenesis, enhancing osteoclastogenesis, and thus leading to higher pathogen colonization as well as higher mortality postinfection. This report of ours is the first to clarify how antibiotic-induced alterations in the gut microbiota may affect bone osseointegration, helping us understand the role of gut microbiota disorders in osteoblastogenesis and osteoclastogenesis following implant insertion with or without infection. Funding Statement: This study was supported by National Natural Science Foundation of China [grant no. 81802182], Guangdong Medical Science Research Foundation [grant no. B2019040], Science and technology program of Guangdong Province [grant no. 2016B090913004], the Innovation Leader Team Program of Guangzhou [grant no.201809010014] and Natural Science Foundation of Guangdong Province [grant no. 2019A1515012115]. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: All animal experiments of ours were approved by Nanfang Hospital Animal Ethics Committee and conducted in accordance with all relevant ethical principles and guidelines set by the Animal Welfare Act and the NIH Guide for Care and Use of Laboratory Animals.

Polysaccharides from Atractylodes macrocephala Koidz. Ameliorate ulcerative colitis via extensive modification of gut microbiota and host metabolism

Turbulence of gut microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids is an important factor in the development of diseases. Many polysaccharides are effective on diseases including ulcerative colitis (UC), yet most studies investigating the mechanisms of polysaccharides mainly focused on their effects on gut microbiota composition and SCFAs, and other metabolites of gut microbiota are often neglected. Here, we examined the effects of polysaccharides from Atractylodes macrocephala Koidz. (AMP) on experimental UC induced by dextran sulfate sodium (DSS) and explored underlying mechanisms of AMP by 16S rDNA-based gut microbiota analysis and untargeted fecal and plasma metabolomics. In addition, a multiscale, multifactorial network was constructed to visualize the mechanisms of AMP. The results showed that AMP significantly increased body weight and ameliorated colonic injury in DSS treated mice. AMP also partly restored the perturbed gut microbiota composition induced by DSS. Untargeted fecal and plasma metabolomics showed that AMP can not only modulate the production of SCFAs by gut microbiota, but also the ability to digest food nutrients, metabolism of amino acids and bile acids, production of cadaverine and other metabolites by hosts and gut microbiota. The study demonstrated that, in addition to SCFAs, AMP can extensively modulate the metabolism of gut microbiota and hosts to achieve the therapeutic effects. This study adds new mechanisms of polysaccharides in treating diseases.

Helicobacter pylori: Perturbation and restoration of gut microbiome

Alternate remedies with natural products provides unlimited opportunities for new drug development. These can be either as pure compounds or as standardized set of compounds. The phytochemicals and secondary metabolites are in great demand for screening bioactive compounds and plays an important role towards drug development. Natural products have many advantages over to synthetic chemical drugs. Helicobacter pylori (H. pylori) a Gram-negative bacteria has been classified as Class I carcinogen by World Health Organization in 1994. Current treatment regimens for H. pylori is ‘triple therapy’ administrated for two weeks which includes a combination of two antibiotics like Amoxicillin and Clarithromycin and a proton pump inhibitor (PPI) like Lansoprazole, and for ‘quadruple therapy’ in addition to antibiotics and a PPI, Bismuth is used. Antibiotic resistance can be named as the main factor for failure of treatment of H. pylori infection. The need of the hour is to develop a herbal remedy that could combat the growth of H. pylori. Probiotics can also be used as ‘feasible’ tool for H. pylori infection management. Present review is an attempt to briefly discuss about the pathogenicity, genetic predisposition, perturbation of gut microbiota due to antibiotic treatment and restoration of healthy gut microbiota with phytochemicals and probiotics.

Sugary drinks, artificially sweetened beverages and cardiovascular disease in NutriNet-Santé cohort

Abstract Introduction Sugary drinks consumption has increased worldwide in recent years and evidence demonstrating their detrimental impact on cardio-metabolic health is accumulating. Artificially sweetened beverages (ASB) are marketed as a healthier alternative, but their cardio-metabolic impact is being debated in the scientific community. This study aimed to investigate the relationships between the consumption of ASB, sugary drinks and the risk of first incident cardiovascular disease (CVD) in a large prospective cohort. Methods The French NutriNet-Santé cohort was launched in 2009. Every 6 months participants are asked to fill 3 validated web-based 24-hour dietary records. All major health events reported by participants were validated based on their medical records by a committee of physicians. Data were also linked to national health insurance system and to the French national cause of specific mortality registry. For each type of beverage, 3 categories were defined as follows: non-consumers, low consumers and high consumers (separated by sex-specific median among consumers). Multi-adjusted Cox proportional hazard models with age as the primary time scale were performed. Results A total of 104,761 participants were included. During follow-up (2009-2019), 1,379 first incident cases of CVD occurred. Compared to non-consumers, higher consumers of sugary drinks had a higher risk of overall CVD (HR = 1.21, 95% CI 1.04 to 1.40, Ptrend=0.009). Higher consumers of ASB had also a significantly higher risk of CVD (HR = 1.30, 95% CI 1.00 to 1.71, Ptrend =0.04). Conclusions Both sugary drinks and ASB were similarly associated with CVD risk. The health effects of non-nutritive sweeteners is currently being debated based on contrasted epidemiological results. Mechanistic data suggests metabolic effects through gut microbiota perturbation and body weight gain. To imply a causal link, they need replication in other large-scale prospective cohort as well as further mechanistic investigations. Key messages Higher consumption of sugary drinks and ASB was associated with higher risk of CVD, suggesting that ASB might not be a healthy substitute for sugary drinks when considering cardiovascular health. These data provide additional arguments to feed the current debate on taxes, labeling and regulation of sugary and artificially sweetened beverages.

A good start in life is important-perinatal factors dictate early microbiota development and longer term maturation.

ABSTRACTMaternal health status is vital for the development of the offspring of humans, including physiological health and psychological functions. The complex and diverse microbial ecosystem residing within humans contributes critically to these intergenerational impacts. Perinatal factors, including maternal nutrition, antibiotic use and maternal stress, alter the maternal gut microbiota during pregnancy, which can be transmitted to the offspring. In addition, gestational age at birth and mode of delivery are indicated frequently to modulate the acquisition and development of gut microbiota in early life. The early-life gut microbiota engages in a range of host biological processes, particularly immunity, cognitive neurodevelopment and metabolism. The perturbed early-life gut microbiota increases the risk for disease in early and later life, highlighting the importance of understanding relationships of perinatal factors with early-life microbial composition and functions. In this review, we present an overview of the crucial perinatal factors and summarise updated knowledge of early-life microbiota, as well as how the perinatal factors shape gut microbiota in short and long terms. We further discuss the clinical consequences of perturbations of early-life gut microbiota and potential therapeutic interventions with probiotics/live biotherapeutics.

White spot syndrome virus (WSSV) disturbs the intestinal microbiota of shrimp (Penaeus vannamei) reared in biofloc and clear seawater.

White spot syndrome virus (WSSV) is one of the most virulent pathogens afflicting shrimp farming. Understanding its influence on shrimp intestinal microbiota is paramount for the advancement of aquaculture, since gut dysbiosis can negatively impact shrimp development, physiology, and immunological response. Thereupon, the data presented herein assesses the influence of WSSV infection and different rearing systems on the intestinal microbiota of Penaeus vannamei. Our study aimed to describe and correlate the composition of shrimp (Penaeus vannamei) gut microbiota, when reared in biofloc and clear seawater, before and (48 h) after WSSV experimental infection. Shrimp were kept in two different systems (biofloc and clear seawater) and experimentally infected with WSSV. Intestine and water samples were characterized by 16S rRNA gene sequencing, before and after viral infection. We observed (i) WSSV induced higher mortality among shrimp reared in biofloc; (ii) WSSV led to a loss of intestinal microbiota heterogeneity, at the genus level, in shrimp kept in clear seawater; (iii) there was a prevalence of Cetobacterium and Bacillus in the intestine of shrimp from both systems; (iv) WSSV did not cause significant changes in intestinal microbiota diversity or richness; (v) regardless of the type of system and time of infection, intestinal microbiota was dissimilar to that of the surrounding water, despite being influenced by the type of system. Therefore, WSSV infection leads to punctual dysbiotic changes in shrimp microbiota, although the virus is sufficiently virulent to cause high mortalities even in well-managed systems, such as a balanced experimental biofloc system. KEY POINTS: • WSSV infection leads to a perturbed gut microbiota in shrimp. • WSSV infection greater impacts microbiota of shrimp reared in CSW than those in BFT. • WSSV infection caused higher mortality levels in shrimp reared in BFT than in CSW. • Rearing system influences shrimp gut microbiota composition. Graphical abstract.

Bugs, breathing and blood pressure: microbiota-gut-brain axis signalling in cardiorespiratory control in health and disease.

There is clear evidence of physiological effects of the gut microbiota on whole-body function in health and disease. Microbiota-gut-brain axis signalling is recognised as a key player in behavioural disorders such as depression and anxiety. Recent evidence suggests that the gut microbiota affects neurocontrol networks responsible for homeostatic functions that are essential for life. We consider the evidence suggesting the potential for the gut microbiota to shape cardiorespiratory homeostasis. In various animal models of disease, there is an association between cardiorespiratory morbidity and perturbed gut microbiota, with strong evidence in support of a role of the gut microbiota in the control of blood pressure. Interventions that target the gut microbiota or manipulate the gut-brain axis, such as short-chain fatty acid supplementation, prevent hypertension in models of obstructive sleep apnoea. Emerging evidence points to a role for the microbiota-gut-brain axis in the control of breathing and ventilatory responsiveness, relevant to cardiorespiratory disease. There is also evidence for an association between the gut microbiota and disease severity in people with asthma and cystic fibrosis. There are many gaps in the knowledge base and an urgent need to better understand the mechanisms by which gut health and dysbiosis contribute to cardiorespiratory control. Nevertheless, there is a growing consensus that manipulation of the gut microbiota could prove an efficacious adjunctive strategy in the treatment of common cardiorespiratory diseases, which are the leading causes of morbidity and mortality.

Protective effect of Lactobacillus salivarius Li01 on thioacetamide-induced acute liver injury and hyperammonaemia.

The gut microbiota plays pivotal roles in liver disease onset and progression. The protective effects of Lactobacillus salivarius Li01 on liver diseases have been reported. In this study, we aimed to detect the protective effect of L. salivarius Li01 on thioacetamide (TAA)-induced acute liver injury and hyperammonaemia. C57BL/6 mice were separated into three groups and given a gavage of L. salivarius Li01 or phosphate-buffered saline for 7days. Acute liver injury and hyperammonaemia were induced with an intraperitoneal TAA injection. L. salivarius Li01 decreased mortality and serum transaminase levels and improved histological liver damage caused by TAA. Serum inflammatory cytokine and chemokine and lipopolysaccharide-binding protein (LBP) concentrations, nuclear factor κB (NFκB) pathway activation and macrophage and neutrophil infiltration into the liver were significantly alleviated by L. salivarius Li01. L. salivarius Li01 also reinforced gut barrier and reshaped the perturbed gut microbiota by upregulating Bacteroidetes and Akkermansia richness and downregulating Proteobacteria, Ruminococcaceae_UCG_014 and Helicobacter richness. Plasma and faecal ammonia levels declined noticeably in the Li01 group, accompanied by improvements in cognitive function, neuro-inflammation and relative brain-derived neurotrophic factor (BDNF) gene expression. Our results indicated that L. salivarius Li01 could be considered a potential probiotic in acute liver injury and hepatic encephalopathy (HE).

Linking perturbations to temporal changes in diversity, stability, and compositions of neonatal calf gut microbiota: prediction of diarrhea.

Perturbations in early life gut microbiota can have long-term impacts on host health. In this study, we investigated antimicrobial-induced temporal changes in diversity, stability, and compositions of gut microbiota in neonatal veal calves, with the objective of identifying microbial markers that predict diarrhea. A total of 220 samples from 63 calves in first 8 weeks of life were used in this study. The results suggest that increase in diversity and stability of gut microbiota over time was a feature of “healthy” (non-diarrheic) calves during early life. Therapeutic antimicrobials delayed the temporal development of diversity and taxa–function robustness (a measure of microbial stability). In addition, predicted genes associated with beta lactam and cationic antimicrobial peptide resistance were more abundant in gut microbiota of calves treated with therapeutic antimicrobials. Random forest machine learning algorithm revealed that Trueperella, Streptococcus, Dorea, uncultured Lachnospiraceae, Ruminococcus 2, and Erysipelatoclostridium may be key microbial markers that can differentiate “healthy” and “unhealthy” (diarrheic) gut microbiota, as they predicted early life diarrhea with an accuracy of 84.3%. Our findings suggest that diarrhea in veal calves may be predicted by the shift in early life gut microbiota, which may provide an opportunity for early intervention (e.g., prebiotics or probiotics) to improve calf health with reduced usage of antimicrobials.

Gut microbiota perturbations and neurodevelopmental impacts in offspring rats concurrently exposure to inorganic arsenic and fluoride

Many “hot spot” geographic areas across the world with drinking water co-contaminated with inorganic arsenic (iAs) and fluoride (F-), two of the most common natural contaminants in drinking water. Both iAs and F- are known neurotoxins and affect neurodevelopment of children. However, very few studies have investigated the neurodevelopmental effects of concurrent exposure to iAs and F-, which could potentially pose a greater risk than iAs or F- exposure alone. Further, perturbations of gut microbiota, which plays a regulatory role in neurodevelopment, resulting from iAs and F- exposure has been reported in numerous studies. There is lacking of information regarding to the relationship among concurrent iAs and F- exposure, microbiome disruption, and neurodevelopmental impacts. To fill these gaps, we treated offspring rats to iAs (50 mg/L NaAsO2) and F- (100 mg/L NaF), alone or combined from early life (in utero and childhood) to puberty. We applied Morris water maze test to assess spatial learning and memory of these rats and generated gut microbiome profiles using 16S rRNA gene sequencing. We showed that concurrent iAs and F- exposure caused more prominent neurodevelopmental effects in rats than either iAs or F- exposure alone. Moreover, Unsupervised Principal Coordinates Analysis (PCoA) and Linear Discriminant Analysis Effect Size (LEfSe) analysis of gut microbiome sequencing results separated concurrent exposure group from others, indicating a more sophisticated change of gut microbial communities occurred under the concurrent exposure condition. Further, a correlation analysis between indices of the water maze test and microbial composition at the genus level identified featured genera that were clearly associated with neurobehavioral performance of rats. 75% (9 out of 12) genera, which had a remarkable difference in relative abundance between the control and combined iAs and F- exposure groups, showed significantly strong correlations (r = 0.70–0.90) with the water maze performance indicators. Collectively, these results suggest that concurrent iAs and F- exposure led to more prominent effects on neurodevelopment and gut microbiome composition structures in rats, and the strong correlation between them indicates a high potential for the development of novel microbiome-based biomarkers of iAs and/or F- associated neurodevelopmental deficits.

Perturbation of gut microbiota decreases susceptibility but does not modulate ongoing autoimmune neurological disease

The gut microbiota regulates the host immune and nervous systems and plays an important role in the pathogenesis of autoimmune neurological disease multiple sclerosis (MS). There are considerable efforts currently being undertaken to develop therapies for MS based on the modulation of microbiota. Evidence from experimental models suggests that the manipulation of microbiota through diet or antibiotics prior to the disease development limits disease susceptibility. However, it is currently unclear if microbiota manipulation therapies would also have an impact on ongoing neurological disease. Here, we examined the effect of antibiotic-based microbiota modulation in spontaneous experimental autoimmune encephalomyelitis (EAE) mouse models of MS before and after the onset of autoimmune disease. Prophylactic antibiotic treatment led to a significant reduction of susceptibility to spontaneous EAE. In contrast, antibiotic treatment after the onset of spontaneous EAE did not show a significant amelioration. These results reveal that the perturbation of gut bacteria alters disease susceptibility but has minimal impact on the ongoing neurological disease.

Disturbance in human gut microbiota networks by parasites and its implications in the incidence of depression

If you think you are in control of your behavior, think again. Evidence suggests that behavioral modifications, as development and persistence of depression, maybe the consequence of a complex network of communication between macro and micro-organisms capable of modifying the physiological axis of the host. Some parasites cause significant nutritional deficiencies for the host and impair the effectiveness of cognitive processes such as memory, teaching or non-verbal intelligence. Bacterial communities mediate the establishment of parasites and vice versa but this complexity approach remains little explored. We study the gut microbiota-parasite interactions using novel techniques of network analysis using data of individuals from two indigenous communities in Guerrero, Mexico. Our results suggest that Ascaris lumbricoides induce a gut microbiota perturbation affecting its network properties and also subnetworks of key species related to depression, translating in a loss of emergence. Studying these network properties changes is particularly important because recent research has shown that human health is characterized by a dynamic trade-off between emergence and self-organization, called criticality. Emergence allows the systems to generate novel information meanwhile self-organization is related to the system’s order and structure. In this way, the loss of emergence means a depart from criticality and ultimately loss of health.

Perturbation of the lipid metabolism and intestinal inflammation in growing pigs with low birth weight is associated with the alterations of gut microbiota

Low birth weight (LBW) is accompanied by metabolic dysfunction, chronic inflammation and gut microbiota perturbation in piglets during early life. Regulating gut microbiota structure can indirectly or directly affect gut health and the host's metabolism. However, whether gut microbiota dysbiosis impact lipid metabolism and inflammation progression in the LBW pigs later in life is unclear. In the present study, we investigated the role of gut microbiota on homeostasis in organisms using young pigs as a model. The plasma concentrations of High-density lipoproteins (HDLC) and pro-inflammatory cytokines such as Interleukin 6 (IL-6), Tumor necrosis factor alpha (TNF-α) and Interleukin 18 (IL-18) were increased in LBW pigs. The bacterial composition was modified dramatically in LBW group in association with an increase in propionate, butyrate and Short-chain fatty acids (SCFAs) in the ileal digesta. LBW impaired intestine results in damaged Fatty acid-binding protein 1 (FABP2) and Fatty acid-binding protein 4 (FABP4) expressions, and the inhibition of Free fatty acid receptor 1 (FFAR1), Free fatty acid receptor 2 (FFAR2) and G protein-coupled receptor 119 (GPR119) expressions, causing inefficient SCFAs absorption. Meanwhile, the physical barrier and chemical barrier related to functional gene expressions of Occludin, Claudin-1, Mucin 1 (MUC1) and Mucin 2 (MUC2) in both ileum and colon were decreased in the LBW pigs. The genera of Blautia, Bifidobacterium, Subdoligranulum and Coprococcus 3 in the ileum were correlated positively with lipid metabolic dysfunction and pro-inflammatory response in LBW pigs. Collectively, the gut microbiota is critical for perturbation of lipid metabolism and inflammatory progression in LBW pigs, which suggests the interventions for modulating bacterial communities may be therapeutically beneficial for metabolic diseases and chronic inflammation.

Treatment of Helicobacter pylori infection and its long-term impacts on gut microbiota.

The rising prevalence of antibiotic resistance and the long-term safety following eradication therapy are important issues in the management of Helicobacter pylori infection. The prevalence of clarithromycin, levofloxacin, and metronidazole resistance of H.pylori has increased to 21%, 27%, and 45%, respectively, in the Asia-Pacific region. Personalized treatment guided by susceptibility testing may provide a reliably excellent eradication rate in the first-line treatment but is costly and not widely available. Population-specific empirical therapy according to the local prevalence of antibiotic resistance may be an alternative strategy. Levofloxacin-based therapy and bismuth quadruple therapy are the recommended second-line rescue therapy. Susceptibility testing or genotypic resistance-guided therapy is the preferred treatment for refractory H.pylori infection, but empirical therapy may be an acceptable alternative. Eradication of H.pylori leads to short-term perturbation of gut microbiota. The diversity of gut microbiota can be restored months after eradication therapy, but the speed of recovery varies with regimens. The short-term increases of antibiotic resistance of Escherichia coli and Klebsiella pneumoniae may be restored to basal states months after H.pylori eradication. Future studies that apply in-depth sequencing, such as shotgun metagenomics sequencing, are needed to clarify whether the compositions of gut microbiota at the species level are fully restored.

Muscovy Duck Reovirus Infection Disrupts the Composition of Intestinal Microbiota in Muscovy Ducklings.

Muscovy duck reovirus (MDRV) is highlypathogenic to young Muscovy ducklings. Although MDRV infection results in ducklings' acute watery diarrhea, the effect of MDRV infection on the composition of host's intestinal microbiota remains poorly understood. This study was conducted to investigate the impacts of MDRV on the composition of Muscovy ducklings' intestinal bacterial community. Three-day-old Muscovy ducklings were inoculated with either the virulent MDRV strain MW9710 or sterile Hank's solution, respectively. The cecal microbiota was analyzed between control and mock MDRV-infected ducklings using Illumina MiSeq sequencing at 6 dpi and 17 dpi, respectively. The results indicated that MDRV infection damaged the intestinal mucosa. In addition, MDRV infection caused severe perturbations of gut microbiota by decreasing microbial richness, altering the abundance of certain genera of the gut microbiota at 6 dpi. Specifically, the relative abundance of short chain fatty acids-producing bacteria (including Shuttleworthia, Streptococcus, and Ruminococcus) was reduced in MDRV-infected ducklings than those of control group, whereas, with an enrichment of Enterobacteriaceae (including Plesiomonas, Escherichia_Shigella and Proteus). Furthermore, microbiota analysis showed that the gut microbiota dysbiosis caused by MDRV infection was basically recovered at 17 dpi. Collectively, this study demonstrated that the gut microbiota of Muscovy ducklings were altered due to MDRV infection, mainly featuring as a net loss of beneficial bacteria and a compensatory proliferation of pathogenic bacteria, which may lead to severe pathology to the intestinal mucosa, and ultimately acute diarrhea. These results will provide insights into the pathology of MDRV infection.

Protective effects of Bifidobacterium adolescentis on collagen-induced arthritis in rats depend on timing of administration.

Emerging studies have addressed the role of probiotics in inflammation modulation via modifying gut microbiota. Perturbed gut microbiota is recognized as a pivotal trigger in the pathogenesis of rheumatoid arthritis (RA), and manipulating gut microbiota at the early phase may be helpful to alleviate the disease based on the fact that dysbiosis occurred prior to clinical arthritis. The current study compared the effects of preventive and therapeutic treatment with Bifidobacterium adolescentis on collagen induced arthritis (CIA) in rats. Early B. adolescentis administration before CIA modelling performed better than late B. adolescentis treatment in reducing the clinical symptoms, rebalancing the pro- and anti-inflammatory responses and maintaining the fecal concentration of short chain fatty acids (SCFAs), as well as restoring the intestinal dysbiosis. Preventive B. adolescentis treatment restored the gut microbiota to a normal level while late B. adolescentis fed rats showed clearly different gut microbial profiles. In addition, there were slight discrepancies between early- and late- treatment of B. adolescentis in the production of specific auto-antibodies and tight junction proteins. All those results highlighted that early treatment of probiotics in arthritis might be a better timing for alleviating arthritis.

Structural and functional alterations of gut microbiome in mice induced by chronic cadmium exposure.

Mammalian gut microbiome is readily affected by acute or subchronic cadmium (Cd) intoxication, but it susceptibility following chronic Cd exposure at environmentally-relevant levels remains unknown. This study comprehensively assessed the effects of Cd exposure at doses of 10 and 50ppm in drinking water for 20 weeks on gut microbiome in mice. Results showed that the Cd exposure induced alterations in gut morphology with potentially increased gut permeability and inflammation. These changes were accompanied by marked perturbation of gut microbiota characterized by significantly decreased gut microbial richness and lowered abundance of short chain fatty acid (SCFA)-producing bacteria, resulting in reduced SCFAs production in the gut. Moreover, the Cd exposure caused substantial metabolic functional changes of the gut microbiome, with significant inhibitions on gene pathways associated with metabolism of amino acid, carbohydrate, and energy, as well as promotions on metabolic pathways such as glutathione metabolism and aminobenzoate degradation. Our findings provide new insights into the hazards assessment of environmental Cd exposure towards gut microbiome.

L-Arabinose Inhibits Colitis by Modulating Gut Microbiota in Mice.

l-Arabinose is a monosaccharide extracted from plants or fibers, which is known to have a variety of functional properties. In this study, we aim to investigate whether l-arabinose could inhibit colitis by modulating gut microbiota. l-Arabinose was administered in mice daily in a dextran sodium sulfate (DSS)-induced colitis model. The histological analysis, disease index, and the expression of inflammatory genes were measured. 16S-rRNA sequence analysis was performed to investigate gut microbiota. Intriguingly, we found that l-arabinose could repress DSS-induced colitis and inhibit p38-/p65-dependent inflammation activation. Besides that, our data revealed that l-arabinose-modulated DSS-induced gut microbiota were disturbed. Additionally, the perturbed gut microbiota was responsible for the suppressive effects of l-arabinose on DSS-induced colitis treated with antibiotics. Lastly, Caco-2 cells were used to confirm the protective effects of l-arabinose in colitis or inflammatory bowel disease. As expected, the protein expression levels in Caco-2 cells of pro-inflammatory genes, which were treated with l-arabinose and incubated with or without tumor necrosis factor alpha. Our work suggested that l-arabinose exerts anti-inflammation effects in DSS-induced colitis. These beneficial effects have correlations with the composition, diversity, and abundance of the gut microbiota regulated by l-arabinose. l-Arabinose could be a remarkable candidate as a functional food or novel therapeutic strategy for intestinal health.

Gut microbiota perturbation is associated with acute sleep disturbance among rectal cancer patients.

Cancer treatment-associatedgut microbial perturbation/dysbiosis has been implicated in the pathobiology of sleep disturbance; however, evidence is scarce. Eighteen newly diagnosed rectal cancer patients (ages 52-81 years; 10 males) completed a sleep disturbance questionnaire and provided stool samples for 16s RNA gene sequencing during chemo-radiotherapy. Descriptive statistics, Wilcoxon test and regression analyses were computed. Regression analyses showed the Shannon's diversity index to be a significant factor associated with sleep disturbance. This preliminary work suggests that the biological "gut-brain axis" mechanism may be associated with symptoms of sleep disturbance.