Interaction between human mucins and parasite glycoproteins: the role of lectins and glycosidases in colonization by intestinal protozoa.

Intestinal mucins are the first line of defense against microorganisms. Although knowledge about the mechanisms involved in the establishment of intestinal protozoa is limited, there is evidence that these parasites produce lectin-like molecules and glycosidases, that exert both, constitutive and secretory functions, promoting the establishment of these microorganisms. In the present review, we analyse the main interactions between mucins of the host intestine and the four main protozoan parasites in humans and their implications in intestinal colonization. There are lectin-like molecules that contain complex oligosaccharide structures and N-acetylglucosamine (GlcNAc), mannose and sialic acid as main components, which are excreted/secreted by Giardia intestinalis, and recognized by the host using mannose-binding lectins (MBL). Entamoeba histolytica and Cryptosporidium spp. express the lectin galactose/N-acetyl-D-galactosamine, which facilitates their adhesion to cells. In Cryptosporidium, the glycoproteins gp30, gp40/15 and gp900 and the glycoprotein lectin CpClec are involved in protozoan adhesion to intestinal cells, forming an adhesion-attack complex. G. intestinalis and E. histolytica can also produce glycosidases such as ß-N-acetyl-D-glucosaminidase, α-d-glucosidase, ß-d-galactosidase, ß-l-fucosidase, α-N-acetyl-d-galactosaminidase and ß-mannosidase. In Blastocystis, α-D-mannose, α-D-glucose, GlcNAc, α-D-fucose, chitin and sialic acid that have been identified on their surface. Fucosidases, hexosaminidases and polygalacturonases, which may be involved in the mucin degradation process, have also been described in the Blastocystis secretoma. Similarly, symbiotic coexistence with the intestinal microbiota promotes the survival of parasites facilitating cell invasion and nutrients obtention. Furthermore, it is necessary to identify and characterize more glycosidases, which have been only partially described by in silico analyses of the parasite genome.

Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension.

Objective The relationship between gut microbiota and portal hypertension remains unclear. We investigated the characteristics of the gut microbiota in portal hypertension patients with esophago-gastric varices and liver cirrhosis. Methods Thirty-six patients (12 patients with portal hypertension, 12 healthy controls, and 12 non-cirrhosis patients) were enrolled in this university hospital study. Intestinal bacteria and statistical analyses were performed up to the genus level using the terminal restriction fragment length polymorphism method targeting 16S ribosomal RNA genes, with diversified regions characterizing each bacterium. Results Levels of Lactobacillales were significantly higher (p=0.045) and those of Clostridium cluster IV significantly lower (p=0.014) in patients with portal hypertension than in other patients. This Clostridium cluster contains many butanoic acid-producing strains, including Ruminococcace and Faecalibacterium prausnitzii. Clostridium cluster IX levels were also significantly lower (p=0.045) in portal hypertension patients than in other patients. There are many strains of Clostridium that produce propionic acid, and the effects on the host and the function of these bacterial species in the human intestine remain unknown. Regarding the Bifidobacterium genus, which is supposed to decrease as a result of cirrhosis, no significant decrease was observed in this study. Conclusion In the present study, we provided information on the characteristics of the gut microbiota of portal hypertension patients with esophago-gastric varices due to liver cirrhosis. In the future, we aim to develop probiotic treatments following further analyses that include the species level, such as the intestinal flora analysis method and next-generation sequencers.

Intestinal Dysbiosis As a Possible Predictor of Very Early Preterm Labor in Pregnant Women With Metabolic Syndrome.

The work assessed the state of the intestinal microbiocenosis in 52 puerperae at the in whom the pregnancy developed against the background of the metabolic syndrome. The diagnosis of metabolic syndrome was determined according to the criteria approved by the World Health Organization for pregnant women. The state of intestinal microbiocenosis was assessed by a bacteriological examination of feces immediately after delivery. The content of the main representatives of the obligate microflora (bifidobacteria, lactobacilli, native intestinal bacilli, fecal streptococci) and facultative (conditionally pathogenic) microorganisms (representatives of the genus Prоteus, Klebsiella, pathogenic strains of E. coli, Staphylococcus epidermidis, Enterobacter, Citrobacter, Clostridium difficile, Candida fungi) was determined. Cultures were made on appropriate growth media. At the time of birth, all patients of group I showed signs of intestinal microbiocenosis disorder. At the same time, 13 (54.2%) puerperae were diagnosed signs of dysbiosis of II degree, 9 (37.5%) with signs of III degree, which were generally characterized by a significant decrease in the content of the main representatives of obligate microflora (Bifidobacterium, Lactobacillus, Escherichia coli, Fecal streptococci) with simultaneous high contamination of Candida albicans and Clostridium difficile. So, it can be considered as a possible predictor of very early preterm birth in women with MS. In pregnant women with MS, but who gave timely birth (group II), dysbiotic disorders were detected to a lesser extent. Thus, in 13 (46.4%) patients, initial signs of intestinal dysbiosis (first degree) were detected in 4 (14.3%) patients (second degree). In 11 (39.3%) puerperae of group II, microbial indices indicated normal eubiotic ratios.

[Role of gut microbiota in carcinogenesis and treatment for colorectal cancer].

Colorectal cancer is one of the most common malignant tumors of digestive tract. There are a large number of microorganisms in the digestive tract. Under normal physiological conditions, intestinal microorganisms can help with digestion and absorption, resist pathogen invasion and regulate the proliferation of intestinal mucosal cells. However, intestinal microflora imbalance will affect the intestinal microenvironment and intestinal cell function, and is closely related to the incidence and progression of colorectal cancer. Firstly, this paper introduces the changes of intestinal flora in patients with colorectal cancer, and then summarizes the mode of intestinal flora participating in the occurrence of colorectal cancer from the macro level. Then, we elaborate the involvement of intestinal flora in colorectal cancer from the aspects of cytokine-dependent chronic inflammation, DNA damage of intestinal epithelial cells, carcinogenic metabolites of intestinal flora and cellular enzymes, and changes of intestinal immune system. The pathogenesis of colorectal cancer provides a reference for further study of the pathogenesis of colorectal cancer. Finally, from the perspective of intestinal flora and colorectal cancer treatment, we analyze the significance of probiotics and bacterial flora transplantation for the treatment of colorectal cancer, and provide some new treatment ideas and methods that may be useful for the treatment of colorectal cancer.

Effects of fermented feeds and ginseng polysaccharides on the intestinal morphology and microbiota composition of Xuefeng black-bone chicken.

Fermented feeds contain abundant organic acids, amino acids, and small peptides, which improve the nutritional status as well as the morphology and microbiota composition of the intestine. Ginseng polysaccharides exhibit several biological activities and contribute to improving intestinal development. Here, Xuefeng black-bone chickens were fed a basal diet fermented by Bacillus subtilis, Saccharomyces cerevisiae, Lactobacillus plantarum, and Enterococcus faecium, with or without ginseng polysaccharides. The 100% microbially fermented feed (Fe) and 100% microbially fermented feed and ginseng polysaccharide (FP) groups showed significantly increased villus height and villus height to crypt depth ratio, and decreased crypt depth in the jejunum. In the 100% complete feed and ginseng polysaccharide (Po) group, the villus height to crypt depth ratio was significantly increased, crypt depth was reduced, and villus height remained unaffected. Next, we studied the intestinal microbial composition of 32 Xuefeng black-bone chickens. A total of 10 phyla and 442 genera were identified, among which Firmicutes, Proteobacteria, and Bacteroidetes were the most dominant phyla. At the genus level, Sutterella and Asteroleplasma abundance increased and decreased, respectively, in the FP and Po groups. Sutterella abundance was positively correlated to villus height and villus height to crypt depth ratio, and negatively correlated to crypt depth, and Asteroleplasma abundance was positively correlated to crypt depth and negatively correlated to villus height to crypt depth ratio. At the species level, the FP group showed significantly increased Bacteroides_vulgatus and Eubacterium_tortuosum and decreased Mycoplasma_gallinarum and Asteroleplasma_anaerobium abundance, and the Po group showed significantly increased Mycoplasma_gallinarum and Asteroleplasma_anaerobium abundance. Moreover, bacterial abundance was closely related to the jejunum histomorphology. Asteroleplasma_anaerobium abundance was positively correlated with crypt depth and negatively correlated with villus height to crypt depth ratio. Mycoplasma_gallinarum abundance was positively correlated to villus height, and Bacteroides_vulgatus and Eubacterium_tortuosum abundance was positively correlated with villus height to crypt depth ratio and negatively correlated with crypt depth. Therefore, fermented feeds with ginseng polysaccharides may be used as effective alternatives to antibiotics for improving intestinal morphology and microbial composition.

Association of worsening of nonalcoholic fatty liver disease with cardiometabolic function and intestinal bacterial overgrowth: A cross-sectional study.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has been associated with small bowel bacterial overgrowth (SIBO) and cardiometabolic dysfunction. This cross-sectional study aimed to evaluate the cardio-metabolic parameters and SIBO in patients with different degrees of hepatic fibrosis estimated by NAFLD fibrosis score (NFS). METHODS: Subjects (n = 78) were allocated to three groups: Healthy control (n = 30), NAFLD with low risk of advanced fibrosis (NAFLD-LRAF, n = 17) and NAFLD with a high risk of advanced fibrosis (NAFLD-HRAF, n = 31). Anthropometrics, blood pressure, electrocardiogram and heart rate variability (HRV) were evaluated. Only the NAFLD-LRAF and NAFLD-HRAF groups were submitted to blood biochemical analysis and glucose hydrogen breath tests. RESULTS: The NAFLD-HRAF group had higher age and body mass index when compared to the control and NAFLD-LRAF groups. The prevalence of SIBO in the NAFLD group was 8.33%. The low frequency/high-frequency ratio (LF/HF ratio) was augmented in NAFLD-LRAF (p < 0.05) when compared with control group. NAFLD-HRAF group had a wide QRS complex (p < 0.05) and reduced LF/HF ratio (p < 0.05) compared to the control and NAFLD-LRAF groups. Serum levels of albumin and platelets were more reduced in the NAFLD-HRAF subjects (p < 0.05) than in the NAFLD-LRAF. CONCLUSIONS: NAFLD impairs cardiac autonomic function. Greater impairment was found in subjects with a worse degree of hepatic fibrosis estimated by NFS. Hypoalbuminemia and thrombocytopenia were higher in subjects with a worse degree of hepatic fibrosis, whereas prevalence of SIBO positive was similar between the groups.

The role of gut microbiome in chemical-induced metabolic and toxicological murine disease models.

The role of gut microbiome in human health and disease is well established. While evidence-based pharmacological studies utilize a variety of chemical-induced metabolic and toxicological disease models that in part recapitulate the natural mode of disease pathogenesis, the mode of actions of these disease models are likely underexplored. Conventionally, the mechanistic principles of these disease models are established as direct tissue toxicity through redox imbalance and pro-inflammatory injury. However, emerging evidences suggest that the mode of action of these chemicals could be largely associated with changes in gut microbial populations, diversity and metabolic functions, affecting pathological changes along the gut-liver and gut-pancreas axis. Especially in these disease models, reversal of disease severity or less sensitivity to induced disease pathogenesis has been observed when germ-free or antibiotic-supplemented microbiota-depleted rodents were treated with disease causing chemicals. Thus, by summarizing evidences from in vivo pharmacological interventions, this review revisits the mode of action of carbon tetrachloride-induced cirrhosis, diethylnitrosamine-induced hepatocellular carcinoma, acetaminophen-induced hepatotoxicity and alloxan- and streptozotocin-induced diabetes through the light of gut microbiota. How changes in gut microbiome affects tissue-level toxicity likely through intestinal-level mechanisms like gastrointestinal inflammation and gut barrier dysfunction has also been discussed. Additionally, this review discusses potential pitfalls of inconsistent experimental models that precludes defining the gut microbial effects in evidence-based pharmacology. Collectively, this review emphasizes the underexplored role of microbial intervention in experimental pharmacology and aims to provide direction towards redefining and establishing microbiome-centric alternative mode of action of chemical-induced metabolic and toxicological disease models in pharmacological research.

Relationship between the composition of the intestinal microbiota and the tracheal and intestinal colonization by opportunistic pathogens in intensive care patients.

OBJECTIVE: Infections caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) are a major issue in intensive care. The intestinal and oropharyngeal microbiota being the reservoir of MDR-GNB. Our main objective was to assess the link between the composition of the intestinal microbiota and the tracheal and intestinal colonization by MDR-GNB, and also by Enterococcus spp. and yeasts. METHODS: We performed a 2-month prospective, monocentric cohort study in the medical intensive care unit of our hospital. Patients ventilated >3 days and spontaneously passing feces were included. A fecal sample and an endotracheal aspiration (EA) were collected twice a week. MDR-GNB but also Enterococcus faecium and yeasts (as potential dysbiosis surrogate markers) were detected by culture methods. The composition of the intestinal microbiota was assessed by 16S profiling. RESULTS: We collected 62 couples of feces and EA from 31 patients, including 18 feces and 9 EA positive for MDR-GNB. Forty-eight fecal samples were considered for 16S profiling. We did not observe a link between the diversity and the richness of the intestinal microbiota and the MDR-GNB intestinal relative abundance (RA). Conversely, we observed a negative link between the intestinal diversity and richness and the RA of Enterococcus spp. (p<0.001). CONCLUSION: The fecal MDR-GNB RA was not associated to the diversity nor the richness of the intestinal microbiota, but that of Enterococcus spp. was.

Acute porcine epidemic diarrhea virus infection reshapes the intestinal microbiota.

The intestinal microbiota is crucial to intestinal homeostasis. Porcine epidemic diarrhea virus (PEDV) is high pathogenic to intestines, causing diarrhea, even death in piglets. To investigate the detailed relationship between PEDV infection and intestinal microbiota, the composition and distribution of intestinal microbiota from pigs were first analyzed using 16S rRNA sequencing technology. The results demonstrated that the composition and distribution of microbes in different intestinal segments were quite similar between 1-week-old and 2-week-old piglets but different from 4-week-old (weaned) piglets. Then piglets at different ages were inoculated with PEDV. The results showed that the 1-week-old piglets exhibited the most severe pathogenicity comparing to the other age groups. Further investigations indicated that Lactobacillus, Escherichia coli, and Lactococcus in the intestinal microbiota of piglets were significantly changed by PEDV infection. These results strengthen our understanding of viruses influencing intestinal microbes and remind us of the potential association between PEDV and intestinal microbes.

Microbiota modulate sympathetic neurons via a gut-brain circuit.

Connections between the gut and brain monitor the intestinal tissue and its microbial and dietary content1, regulating both physiological intestinal functions such as nutrient absorption and motility2,3, and brain-wired feeding behaviour2. It is therefore plausible that circuits exist to detect gut microorganisms and relay this information to areas of the central nervous system that, in turn, regulate gut physiology4. Here we characterize the influence of the microbiota on enteric-associated neurons by combining gnotobiotic mouse models with transcriptomics, circuit-tracing methods and functional manipulations. We find that the gut microbiome modulates gut-extrinsic sympathetic neurons: microbiota depletion leads to increased expression of the neuronal transcription factor cFos, and colonization of germ-free mice with bacteria that produce short-chain fatty acids suppresses cFos expression in the gut sympathetic ganglia. Chemogenetic manipulations, translational profiling and anterograde tracing identify a subset of distal intestine-projecting vagal neurons that are positioned to have an afferent role in microbiota-mediated modulation of gut sympathetic neurons. Retrograde polysynaptic neuronal tracing from the intestinal wall identifies brainstem sensory nuclei that are activated during microbial depletion, as well as efferent sympathetic premotor glutamatergic neurons that regulate gastrointestinal transit. These results reveal microbiota-dependent control of gut-extrinsic sympathetic activation through a gut-brain circuit.

Effects of woody forages on biodiversity and bioactivity of aerobic culturable gut bacteria of tilapia (Oreochromis niloticus).

The present study investigated the effects of four woody forages (Moringa oleifera Lam (MOL), fermented MOL, Folium mori (FM) and fermented FM) on biodiversity and bioactivity of aerobic culturable gut bacteria of tilapia (Oreochromis niloticus) by a traditional culture-dependent method. A total of 133 aerobic culturable isolates were recovered and identified from the gut of tilapia, belonging to 35 species of 12 genera in three bacterial phyla (Firmicutes, Actinobacteria and Proteobacteria). Among them, 6 bacterial isolates of Bacillus baekryungensis, Bacillus marisflavi, Bacillus pumilus, Bacillus methylotrophicus, Proteus mirabilis and Pseudomonas taiwanensis were isolated from all the five experimental groups. The Bray-Curtis analysis showed that the bacterial communities among the five groups displayed obvious differences. In addition, this result of bioactivity showed that approximate 43% of the aerobic culturable gut bacteria of tilapia displayed a distinct anti-bacterial activity against at least one of four fish pathogens Streptococcus agalactiae, Streptococcus iniae, Micrococcus luteus and Vibrio parahemolyticus. Furthermore, Bacillus amyloliquefaciens and Streptomyces rutgersensis displayed strong activity against all four indicator bacteria. These results contribute to our understanding of the intestinal bacterial diversity of tilapia when fed with woody forages and how certain antimicrobial bacteria flourished under such diets. This can aid in the further exploitation of new diets and probiotic sources in aquaculture.

Bacillus subtilis PB6 based probiotic supplementation plays a role in the recovery after the necrotic enteritis challenge.

In poultry production, birds are raised under intensive conditions, which can enable rapid spread of infections, with Clostridium perfringens-caused necrotic enteritis (NE) being one of the most devastating for the industry. The current investigation was conducted to evaluate the effectiveness of Bacillus subtilis PB6 probiotic supplementation on bird's post NE recovery, based on chicken performance, cecal microbiota composition, ileum histomorphometric measurements, and short-chain fatty acid production in the cecum of the birds that were challenged with NE mid-production. Birds were split into four groups, including a negative control, positive control challenged with C. perfringens, group supplemented with B. subtilis probiotic, and NE challenged birds supplemented with B. subtilis probiotic. Following NE challenge birds were allowed to reach the end of production time at 40 days, and samples were collected to estimate if probiotic supplementation resulted in better post-NE recovery. Intestinal lesion score across the duodenum, jejunum, and ileum indicated that at the end of production timeline NE challenged birds supplemented with B. subtilis probiotic had lower intestinal lesion scores compared to NE challenged birds without probiotic supplementation implying improved recovery. Probiotic supplementation improved performance of NE challenged birds only in the post-NE recovery stage. NE challenged birds had a significant increase in cecal propionic acid, which was not observed in NE challenged birds supplemented with B.subtilus. Both B. subtilis supplemented groups (challenged and unchanged) were characterized by a significant rise in cecal acetic and butyric acid. Our results demonstrate that B. subtilis supplementation can assist the birds in dealing with NE outbreak and long term recovery.

Association of intestinal colonization of ESBL-producing Enterobacteriaceae in poultry slaughterhouse workers with occupational exposure-A German pilot study.

BACKGROUND: Bacteria that have acquired antimicrobial resistance, in particular ESBL-producing Enterobacteriaceae, are an important healthcare concern. Therefore, transmission routes and risk factors are of interest, especially for the carriage of ESBL-producing E. coli. Since there is an enhanced risk for pig slaughterhouse employees to carry ESBL-producing Enterobacteriaceae, associated with animal contact as potential risk factor, the present study investigated the occurrence of ESBL-producing Enterobacteriaceae in poultry slaughterhouse employees. Due to the higher level of resistant Enterobacteriaceae in primary poultry production than in pig production, a higher risk of intestinal colonization of poultry slaughterhouse employees was expected. RESULTS: ESBL-producing Enterobacteriaceae were detected in 5.1% (5 of 99) of the fecal samples of slaughterhouse workers. The species of these isolates was confirmed as E. coli. PCR assays revealed the presence of the genes blaCTX-M-15 (n = 2) and blaSHV-12 (n = 3) in these isolates, partly in combination with the ß-lactamase gene blaTEM-135. Participants were divided into two groups according to their occupational exposure and results indicated an increased probability of colonization with ESBL-producing Enterobacteriaceae for the group of 'higher exposure' (OR 3.7, exact 95% CI 0.6-23.5; p = 0.4). For intestinal colonization with ESBL-producing Enterobacteriaceae, a prevalence of 10% (3/30) was observed in the group of 'higher exposure' versus 2.9% (2/69) in the group of 'lower exposure'. Employees in working steps such as 'hanging' poultry in the process of slaughter and 'evisceration' seemed to have a higher risk for intestinal colonization with ESBL-producing Enterobacteriaceae compared to the group of 'lower exposure'. CONCLUSION: This study is the first of its kind to collect data on the occupational exposure of slaughterhouse workers to ESBL-producing Enterobacteriaceae in Europe. The results suggested that colonization with ESBL-producing Enterobacteriaceae is associated with occupational exposure in poultry slaughterhouses. However, the presence of ESBL-producing E. coli isolates in only 5.1% (5/99) of the tested employees in poultry slaughterhouses suggests a lower transmission risk than in pig slaughterhouses.

[Practice and consideration of fecal microbiota transplantation].

As an innovative therapy, FMT has made a breakthrough in the treatment of recurrent Clostridium difficile infection (CDI). With the rapid development of biotechnology, the relationship between intestinal microflora and diseases has been gradually eluciated. Great hope has also been given to FMT in other intestinal and extraintestinal diseases with ineffective traditional treatment. However, as a new therapy method, FMT still has many unknown fields, such as the selection of clinical donors, the preparation of standardized bacterial solution and capsule, the selection of indications, the matching of donor and receptor, and the prevention and treatment of complications. Since 2012, our center has carried out treatment research and practice of FMT, so far with more than 60 000 FMTs for more than 3500 cases. Based on large sample data and experience, this special issue reports and discusses the above topics, and focuses on the establishment and clinical application of standardized methodology of FMT, which will undoubtedly play a positive role in promoting the healthy development of FMT treatment in China.

[Changes of intestinal flora after gastrointestinal surgery: clinical significance of intestinal environment reconstruction].

The intestinal flora of patients after gastrointestinal surgery is in a state of disorder, which may affect the surgical efficacy and prognosis. Timely and effective reconstruction of microbiota balance is very important for reducing postoperative complications, ensuring the recovery of gastrointestinal function and improving quality of life. The purpose of this article is to explore the effect of gastrointestinal surgery on intestinal flora and the clinical significance of microbiota balance reconstruction.

[Pay attention to the diagnosis and treatment of intestinal infectious diarrhea after colorectal surgery].

Colorectal surgery patients have severe intestinal flora disorders and antibiotic resistant bacteria due to the disease itself and preoperative treatment, as well as the influence of dietary structure and environmental factors. Perioperative anesthesia and operative stress can cause gastrointestinal motility disorders. In addition, the widespread use of prophylactic broad-spectrum antibiotics and antiacids aggravate intestinal flora disorders and induces severe postoperative infectious diarrhea, such as pseudomembranous enteritis and fatal enteritis. The clinical manifectation are severe infectious diarrhea with high fever and abdominal distension after surgery. The disease progresses rapidly. When the diagnosis and treatment are delayed, the patient can quickly develop shock and other serious complications such as anastomotic leakage, even die of multiple organ failure. Therefore, early diagnosis and treatment are crucial.

Characterization of native Escherichia coli populations from bovine vagina of healthy heifers and cows with postpartum uterine disease.

Even though Escherichia coli are common bacteria of the bovine vaginal microbiota, they represent an important pathogen that causes diseases in the reproductive tract and subfertility. However, the actual endometrial virulence profile of E. coli is poorly understood. The present study aims to characterize the phylogenetic structure and virulence potential of native vaginal populations of E. coli from healthy heifers (H), and cows with postpartum uterine diseases (PUD), such as metritis/endometritis (MT) or repeat breeder cows (RB). To this end, the virulence repertoire of 97 E. coli isolates was genotypically and phenotypically assessed. Most of them were assigned to phylogenetic group A (74%), followed by B1 (17%) and D (9%); RB strains were significantly (p < 0.05) more represented by B1. Seven of the 15 evaluated virulence genes (VFG) were detected and the most prevalent were fimH (87%), agn43 (41%) and csgA (35%); while traT (27%), fyuA (11%), hlyA (5%) and kpsMT II (5%) were observed in a lower proportion. Particularly, fyuA was significantly higher (p < 0.05) in MT cows whereas csgA showed the same behavior in PUD animals (p < 0.05). When comparing H and PUD strains, these last ones were associated to positive expression of biofilm, fimbriae curli/cellulose and motility; yet RB strains did not show motility. Vaginal B1 E. coli populations, that possess VFG (fyuA and csgA) as well as the expression of motility, curli fimbriae/cellulose and biofilm, may represent risk factors for endometrial disorders; specifically, those that also, have kpsMT II may have a pathogenic potential for causing the RB syndrome. Future research focusing on the detection of these strains in the vaginal microbiota of cows with postpartum uterine diseases should be done since the control of their presence in vagina could reduce the risk that they access the uterus during the postpartum period.

A neurotransmitter produced by gut bacteria modulates host sensory behaviour.

Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms1. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts2,3. However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine ß-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia, and show that these genes are necessary for the modulation of host behaviour. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.

Upregulation of virulence genes promotes Vibrio cholerae biofilm hyperinfectivity.

Vibrio cholerae remains a major global health threat, disproportionately impacting parts of the world without adequate infrastructure and sanitation resources. In aquatic environments, V. cholerae exists both as planktonic cells and as biofilms, which are held together by an extracellular matrix. V. cholerae biofilms have been shown to be hyperinfective, but the mechanism of hyperinfectivity is unclear. Here we show that biofilm-grown cells, irrespective of the surfaces on which they are formed, are able to markedly outcompete planktonic-grown cells in the infant mouse. Using an imaging technique designed to render intestinal tissue optically transparent and preserve the spatial integrity of infected intestines, we reveal and compare three-dimensional V. cholerae colonization patterns of planktonic-grown and biofilm-grown cells. Quantitative image analyses show that V. cholerae colonizes mainly the medial portion of the small intestine and that both the abundance and localization patterns of biofilm-grown cells differ from that of planktonic-grown cells. In vitro biofilm-grown cells activate expression of the virulence cascade, including the toxin coregulated pilus (TCP), and are able to acquire the cholera toxin-carrying CTXФ phage. Overall, virulence factor gene expression is also higher in vivo when infected with biofilm-grown cells, and modulation of their regulation is sufficient to cause the biofilm hyperinfectivity phenotype. Together, these results indicate that the altered biogeography of biofilm-grown cells and their enhanced production of virulence factors in the intestine underpin the biofilm hyperinfectivity phenotype.