Gut Microbes

There is a paucity of research conducted on microbial prevalence in pheasants. The microbiota of captive birds has zoonotic significance and must be characterize. Present study is therefore planned to assess the microbiota from oral, fecal and gut content of captive avian species. It will be helpful in characterization of harmful microbes. Different samples taken from oral, gut and feces of ring-necked pheasants (Phasianus colchicus), green pheasants (Phasianus versicolor), golden pheasant (Chrysolophus pictus) and silver pheasant (Lophura nycthemera). Samples were collected, diluted, and inoculated onto different agar plates (MacConkey, SS agar, MSA and nutrient agar) for cultivation of bacterial species. Colonies of E.coli, Staphylococcus spp. Brachyspira spp. and Campylobacter spp were observed based on colony morphology. Colony forming unit showed E. coli as frequently found bacteria in fecal, oral and gut contents of all the above pheasants. The overall significance difference was found among bacterial species of golden pheasants, green pheasant, ring-necked pheasant, and silver pheasants. It was concluded that E.coli is predominant isolated from heathy pheasants followed by Campylobacter, Staphylococcus and Brachyspira.

Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bifidobacterium species autochthonous to the infant gut and one Lacticaseibacillus strain on the compositional and functional trajectory of microbiome. Probiotic treatment accelerated the transition to a mature, term-like microbiome with higher stability and species interconnectivity. Besides infant age, probiotic Bifidobacterium strains and stool metabolites were the best predictors of microbiome maturation, and structural equation modeling confirmed probiotics as a major determinant for the trajectory of microbiome assembly. Probiotic-driven microbiome maturation was also linked to an improved, anti-inflammatory intestinal immune milieu. This demonstrates that Bifidobacterium strains function as ecosystem engineers that lead to an acceleration of microbiome maturation and immunological benefits in extremely premature infants.

Background Campylobacter (C.) species are the most common bacterial cause of foodborne diarrhea in humans. Despite colonization, most animals do not show clinical signs, making recognition of affected flocks and disruption of the infection chain before slaughter challenging. Turkeys are often cocolonized with C. jejuni and C. coli. To understand the pathogen-host-interaction in the context of two different Campylobacter species, we compared the colonization patterns and quantities in mono- and co-colonized female commercial turkeys. In three repeated experiments we investigated the impact on gut morphology, functional integrity, and microbiota composition as parameters of gut health at seven, 14, and 28 days post-inoculation. Results Despite successful Campylobacter colonization, clinical signs or pathological lesions were not observed. C. coli persistently colonized the distal intestinal tract and at a higher load compared to C. jejuni. Both strains were isolated from livers and sp...

Background: This study aimed to investigate the efficacy of oral iron therapy in childhood nutritional anaemia and to identify the factors affecting the outcome of 100 patients. Data was collected from the medical records of the patients. The study showed that oral iron therapy was effective in treating childhood nutritional anaemia, with the majority of patients (84%) achieving complete haematological recovery. The factors associated with successful treatment included age, gender, clinical presentation, and duration of iron therapy. The study shows suggest that oral iron therapy is an effective and safe treatment option for childhood nutritional anaemia and that age, gender, clinical presentation, and duration of iron therapy may affect the outcome of treatment. Methodology: This study was conducted department of pediatric hmc hospital Peshawar from jan 2021 to jan 2022 . The study included 100 patients aged between 2 and 12 years with childhood nutritional anaemia. Data was collec...

The gut microbiota of humans is essential for maintaining good health because it interacts in many ways with the host. This study explores shortchain fatty acids (SCFAs), their similar metabolic molecules in the gut, and their roles in metabolic, nervous, and immune functions. To find out how wellness markers are linked to certain microbes in your gut, this research tests stool samples and carries out 16S rRNA sequencing and metabolomics. It was found that an increase in butyrate and propionate levels leads to less general inflammation and better blood markers for health. Likewise, other neurotransmitters in microbes, especially gamma-aminobutyric acid (GABA) and serotonin, have been connected to better cognition and improved mood. The findings indicate that gut biochemistry plays a key part in communication between gut and brain or immune systems, offering new approaches for using microbiomes for treatment and diagnosis. According to the research, working with nutrition and the microbiota in different groups can improve overall health results.

Gut microbiota represents a therapeutic target for obesity. We hypothesize that B. uniformis CECT 7771 combined with wheat bran extract (WBE), its preferred carbon source, may exert superior antiobesity effects. We performed a 17-week intervention in diet-induced obese mice receiving either B. uniformis, WBE, or their combination to identify interactions and independent actions on metabolism and immunity. B. uniformis combined with WBE was the most effective intervention, curbing weight gain and adiposity, while exerting more modest effects separately. The combination restored insulin-dependent metabolic routes in fat and liver, although the bacterium was the primary driver for improving whole-body glucose disposal. Moreover, B. uniformis-combined with WBE caused the highest increases in butyrate and restored the proportion of induced intraepithelial lymphocytes and type-3 innate lymphoid cells in the intestinal epithelium. Thus, strengthening the first line of immune defense against unhealthy diets and associated dysbiosis in the intestine. This intervention also attenuated the altered IL22 signaling and liver inflammation. Our study shows opportunities for employing B. uniformis, combined with WBE, to aid in the treatment of obesity.

Background Ailments such as diarrhoea and antibiotic-associated gut symptoms are generally self-managed using probiotics. Real-world data on reasons behind self-medication with over-the-counter (OTC) products and patient-reported outcomes can be investigated strategically by the pharmacists. Objective This study evaluates the use of Bacillus clausii (Enterogermina ® ) at the Italian community pharmacies among self-medicating patients, their treatment habits and perceived benefits. Design This is a multicentre, prospective, non-interventional study which included two visits [at screening (T0) and end of the study (T1) when symptoms had subsided, ≤ 30 days from T0]. Patients who were already inclined to buy B. clausii were enrolled and instructed to complete a questionnaire at T0 and T1. The primary objective was to evaluate the reasons for taking B. clausii. Secondary objectives assessed treatment duration, perceived effectiveness, quality of life (QoL), treatment satisfaction and safety outcomes. Results Overall, 268 patients were enrolled; 99.6% of them were evaluated at T0 and 97.4% at T1, and safety was evaluated in 97.8% who had ≥ 1 dose of B. clausii. At T0, mean age was 50.7 years and majority were females (62.2%). In the interview, main reason stated for using B. clausii at T0 was diarrhoea (56.93%), followed by other gastrointestinal symptoms. Treatment duration was shorter in those with diarrhoea or abdominal pain versus those with constipation or abdominal tension. More than 90% perceived their symptoms to have improved or improved very much. Overall QoL improved in all the aspects measured. Treatment satisfaction was reported by nearly 90% of patients as satisfied, very satisfied or extremely satisfied. No adverse events were reported. Conclusion This is the first pharmacy-based study in Italy that evaluated the real-world usage of an OTC probiotic containing B. clausii among self-medicating adults. Diarrhoea was the most common reason for use, with high-level of perceived effectiveness and patient satisfaction with B. clausii.

Background Diatomite is a source of biologically available silicon but in feed industry its insecticide and anti-caking properties have been also widely recognized. The aim of the study was to evaluate the effect of dietary diatomitebentonite mixture (DBM) supplementation on the quantitative and qualitative composition of the bacterial microbiome of the broiler chicken gut. The trial was carried out on 960 Ross 308 broiler chickens divided into 2 experimental groups throughout the entire rearing period lasting 6 weeks. The birds were fed complete granulated diets without (group C) or with DBM (group E) in an amount of 1% from the 11 day of life. Two nutritionally balanced diets were used, tailored to the age of the broilers: a grower diet (from day 11 to 34) and a finisher diet (from day 35 to 42 of life). Diatomite used in a mixture with bentonite significantly altered the microbiome. Restricting the description to species that comprise a minimum of 1% of all analyzed sequences, 36 species in group E (with diatomite) and 30 species in group C (without diatomite) were selected. Several bacteria species were identified in intestinal contents of chickens for the first time. Thirteen species occurred only in group E:

Acute appendicitis is the most frequent surgical abdominal emergency, but its etiology remains poorly understood. Histological examination of the appendix, following its removal due to acute appendicitis, consistently shows features in common with bronchial asthma, pointing to an allergic reaction as a candidate etiologic factor. Here we have developed the concept of appendicular lavage and used it to study the levels of key Th2 cytokines, IL-4, IL-5 and IL-9 in patients with a clinical diagnosis of acute appendicitis. The study group consisted of 20 phlegmonous appendicitis, 13 gangrenous appendicitis, and a control group of 8 patients with clinical diagnosis of appendicitis but with normal histology. Cytokines levels are higher in acute appendicitis. The difference was clearer when comparing phlegmonous appendicitis with non-pathological appendix (p=0,01), respectively 48,3 vs 21,3; 29,2 vs 8,0; 34,1 vs 16,6 pg/mL for IL-4, IL-5 and IL-9. This Th2 cytokine profile is compatible wi...

Gastrointestinal (GI) dysfunction has been reported in a substantial number of children with autism spectrum disorders (ASD). Activation of the mucosal immune response and the presence of abnormal gut microbiota are repeatedly observed in these children. In children with ASD, the presence of GI dysfunction is often associated with increased irritability, tantrums, aggressive behaviour, and sleep disturbances. Moreover, modulating gut bacteria with short-term antibiotic treatment can lead to temporary improvement in behavioral symptoms in some individuals with ASD. Probiotics can influence microbiota composition and intestinal barrier function and alter mucosal immune responses. The administration of probiotic bacteria to address changes in the microbiota might, therefore, be a useful novel therapeutic tool with which to restore normal gut microbiota, reduce inflammation, restore epithelial barrier function, and potentially ameliorate behavioural symptoms associated with some children with ASD. In this review of the literature, support emerges for the clinical testing of probiotics in ASD, especially in the context of addressing GI symptoms. Gastroenterology Research and Practice prominent subgroup of individuals with ASD suffers from gastrointestinal (GI) dysfunction that stems from yet unknown causes. The prevalence of GI symptoms in ASD is substantial, with common syptoms including diarrhea, constipation, vomiting/reflux, abdominal pain/discomfort, gaseousness, and unusually foul-smelling stools . Individuals with ASD who have GI symptoms, compared to those without GI symptoms, often display significantly higher measures of irritability, anxiety, and social withdrawal . While these studies illustrate that GI symptoms are present, the pathophysiology of these symptoms is not well understood. Despite the current lack of evidence surrounding a known GI pathology in ASD, almost one-fifth of the physicians encourage the use of probiotics for children with ASD, according to a recent survey in the United States . In addition, almost 60 percent of the physicians accept the use of probiotics when the family is already utilizing them. Thus, the purpose of this paper is to put forth whether there is a case for clinical testing of probiotic preparations in selected groups of children with ASD. Rationale will be presented for the relevance of probiotic use not only in groups with GI symptoms but also in light of other immunologic and intestinal abnormalities identified in the ASD population. Probiotics are living nonpathogenic microorganisms, which beneficially affect the host's health, when administered in adequate amounts as food ingredient or supplement. Probiotic products consist mainly of lactic acid-producing bacteria, such as lactobacilli, lactococci, and bifidobacteria, or yeasts such as Saccharomyces boulardii. The wellestablished health effects of probiotics vary with the species and particular strain(s) of bacteria chosen, based on genetic differences and the nature of bacteria-host interactions . Probiotics have been used safely in the fermentations of food products for decades. Therefore, the United States Food and Drug Administration has designated probiotics as Generally Recognized as Safe (GRAS), and the European authorities provide a list of bacterial species with a Qualified Presumption of Safety (QPS). Research on probiotics has shown efficacy of probiotic bacteria in a wide variety of health problems. Gastrointestinal difficulties such as antibiotic-associated and acute infectious diarrhea, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) have been shown to be responsive to probiotics. In addition, probiotics have also shown activity in influencing the host's immune system . With the growing research on probiotics and the integral part they play in the health of not just the GI tract but the body as a whole, their inclusion as an integrative treatment may be of use for children with ASD.

Alterations in the human gut bacteriome can be associated with human health issues, such as type-2 diabetes and cardiovascular disease. Both external and internal factors can drive changes in the composition and in the interactions of the human gut bacteriome, impacting negatively on the host cells. In this paper, we focus on the human gut bacteriome metabolism and we propose a two-layer network system to investigate its dynamics. Furthermore, we develop an in-silico simulation model (virtual GB), allowing us to study the impact of the metabolite exchange through molecular communications in the human gut bacteriome network system. Our results show that the regulation of molecular inputs can strongly affect bacterial population growth and create an unbalanced network, as shown by the shift in the node weights based on the molecular signals that are produced. Additionally, we show that the metabolite molecular communication production is greatly affected when directly manipulating the composition of the human gut bacteriome network in the virtual GB. These results indicate that our human GB interaction model can help to identify hidden behaviors of the human gut bacteriome depending on the molecular signal interactions. Moreover, the virtual GB can support the research and development of novel medical treatments based on the accurate control of bacterial growth and exchange of metabolites.

Insect larvae are increasingly being employed as sophisticated infection models in the expanding field of pathogenic bacterial research. This innovative study aims to evaluate an alternative model for analyzing host-pathogen interactions and assessing the efficacy of antimicrobial treatments using the biological system of Rhynchophorus phoenicis larvae. Using PCR techniques targeting 16S rRNA, virulence genes encoding Type III secretion system (T3SS) components, and the Hsp60 gene, four major pathogenic Enterobacteriaceae were identified with 100% detection rates: Salmonella Typhimurium, Klebsiella pneumoniae, Enterobacter cloacae, and enteropathogenic Escherichia coli (EPEC). Virulence assessment revealed that injection of bacterial strains at a concentration of 10 5 CFU/µL into R. phoenicis larvae was optimal for evaluating pathogenicity. Highly virulent strains-E. coli EPEC strain E2, K. pneumoniae K4, S. Typhimurium S4, and E. cloacae En2-caused significantly reduced larval survival, with bacterial loads in the hemolymph reaching up to 2.5 × 10 6 CFU/µL. Treatment evaluation showed that the amoxicillin + biosurfactant combination was the most effective in prolonging larval survival across all time points. Survival rates peaked at 80% at 24 h and remained relatively high at up to 70% at 72 h for certain strains. In contrast, amoxicillin alone demonstrated variable and less sustained efficacy. These findings underscore the potential of R. phoenicis larvae as a valuable alternative model for exploring host-pathogen interactions and assessing the synergistic efficacy of combined antimicrobial treatments involving antibiotics and biosurfactants. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

I rritable bowel syndrome (IBS) is a clinically heterogeneous disorder which is likely to involve a number of causative factors. The contribution of altered intestinal microbiota composition or function to this disorder is controversial, and is the subject of much current research. Until recently, the technical limitations of the methodologies available have not permitted an adequate survey of low-abundance microbial species. Recent technological developments have enabled the analysis of the global population of the microbiome using high through-put, culture independent, 16S rRNA amplicon pyrosequencing. Using these new methodologies, we are able to gain important biological insights into the link between functional bowel disorders and the microbiome. This addendum contextualizes and summarizes the results of these studies, and defines the future challenges and opportunities in the field. Until recently, studies dealing with microbial alterations in IBS have looked at a

Preterm neonates are at high risk of infectious and inflammatory diseases which require antibiotic treatment. Antibiotics influence neonatal gut microbiome development, and intestinal dysbiosis has been associated with delayed gastrointestinal transit. Neonates who take less time to pass meconium have a better tolerance to enteral feeding. We analyzed the effect of neonatal antibiotic treatment on the stool pattern and oral tolerance in 106 preterm infants < 33 weeks gestational age. Neonates were classified in 3 groups according to neonatal antibiotic (ABT) treatment days: no antibiotics, 3–7 d ABT, and ≥8 d ABT. Preterm infants from the ≥8 d ABT group took longer to pass meconium and to start green and yellow stools, took longer to reach 100 and 150 mL/kg/day, and reached reduced volumes in enteral feeds at day of life 14 and 28 than infants from no ABT and 3–7 d ABT groups. Multiple linear regression models showed that neonatal antibiotic treatment, birth weight, invasive mech...

Emerging evidence has suggested that gut microbiota dysbiosis may have a role in colorectal cancer (CRC) progression. Dietary intake high in plant protein and fiber has been associated with reduced risk of this cancer through modulation of gut microbiota. This study aimed to evaluate the effect of the soy protein and fiber diet on gut Lactobacillus and Bifidobacterium of azoxymethane/dextran sodium sulfate (AOM/DSS)induced rat. A total of twenty-five Wistar rats aged eight weeks were randomly assigned into five groups: the normal control group (NC), the AOM/DSS group, the high protein diet +AOM/DSS group (HP), the high fiber diet +AOM/DSS group (HF), and the combination soy protein and fiber diet+ AOM/DSS group (PF). CRC was induced by injecting 12 mg/kg BW per week of AOM and adding 2% DSS into the drinking water. After four weeks, the rats were sacrificed, and the total DNA was isolated from the cecum. The relative abundance of Lactobacillus and Bifidobacterium was analyzed using quantitative real-time PCR. The fecal cecum samples analysis demonstrated that rats receiving a high soy protein diet (HP), high fiber diet (HF), or both diets (PF) have significantly higher Lactobacillus count compared with the AOM/DSS group that only received a standard diet. In the case of Bifidobacterium, both HP and PF diets showed higher abundance relative to AOM/DSS group, though it was not significant. In conclusion, dietary intake consisting of high soy protein, fiber, or a combination of the two diets modulates the gut microbiota of AOM/DSS-treated rats.

The identification and characterization of clinical Clostridioides difficile isolates with reduced fidaxomicin susceptibility. Methods: Agar dilution assays were used to determine fidaxomicin MICs. Genome sequence data were obtained by single-molecule real-time (SMRT) sequencing in addition to amplicon sequencing of rpoB and rpoC alleles. Allelic exchange was used to introduce the identified mutation into C. difficile 630Derm. Replication rates, toxin A/B production and spore formation were determined from the strain with reduced fidaxomicin susceptibility. Results: Out of 50 clinical C. difficile isolates, isolate Goe-91 revealed markedly reduced fidaxomicin susceptibility (MIC .64 mg/L). A V1143D mutation was identified in rpoB of Goe-91. When introduced into C. difficile 630Derm, this mutation decreased fidaxomicin susceptibility (MIC .64 mg/L), but was also associated with a reduced replication rate, low toxin A/B production and markedly reduced spore formation. In contrast, Goe-91, although also reduced in toxin production, showed normal growth rates and only moderately reduced spore formation capacities. This indicates that the rpoB V1143D allele-associated fitness defect is less pronounced in the clinical isolate. Conclusions: To the best of our knowledge, this is the first description of a pathogenic clinical C. difficile isolate with markedly reduced fidaxomicin susceptibility. The lower-than-expected fitness burden of the resistancemediating rpoB V1143D allele might be an indication for compensatory mechanisms that take place during in vivo selection of mutants.

Background and aims Nutritional therapy with the Crohn’s Disease Exclusion Diet + Partial Enteral Nutrition [CDED+PEN] or Exclusive Enteral Nutrition [EEN] induces remission and reduces inflammation in mild-to-moderate paediatric Crohn’s disease [CD]. We aimed to assess if reaching remission with nutritional therapy is mediated by correcting compositional or functional dysbiosis. Methods We assessed metagenome sequences, short chain fatty acids [SCFA] and bile acids [BA] in 54 paediatric CD patients reaching remission after nutritional therapy [with CDED + PEN or EEN] [NCT01728870], compared to 26 paediatric healthy controls. Results Successful dietary therapy decreased the relative abundance of Proteobacteria and increased Firmicutes towards healthy controls. CD patients possessed a mixture of two metabotypes [M1 and M2], whereas all healthy controls had metabotype M1. M1 was characterised by high Bacteroidetes and Firmicutes, low Proteobacteria, and higher SCFA synthesis pathways,...

We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months). Moreover, the detected viral populations of donor and patient exhibited comparable diversity and richness. These findings were unexpected since enteric viromes are normally highly variable, assumed to influence the bacterial host community and change with environmental conditions. In contrast to the virome, the bacterial microbiota varied indeed for more than 7 months with ongoing dysbiosis before it reached donor similarity. Our findings that are based on sequence information and protein domain analysis seem to suggest that stable phage properties correlate with successful FMT better than the changing bacterial communities. We speculate that we here preferentially detected a stable core virome, which dominated over a variable flexible virome that may have been too heterogeneous for experimental detection or was underrepresented in the databases. It will be interesting to analyze whether the enteric virome allows predictions for the clinical outcome of FMT for rCDI and other diseases such as inflammatory bowel disease or obesity.

We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months). Moreover, the detected viral populations of donor and patient exhibited comparable diversity and richness. These findings were unexpected since enteric viromes are normally highly variable, assumed to influence the bacterial host community and change with environmental conditions. In contrast to the virome, the bacterial microbiota varied indeed for more than 7 months with ongoing dysbiosis before it reached donor similarity. Our findings that are based on sequence information and protein domain analysis seem to suggest that stable phage properties correlate with successful FMT better than the changing bacterial communities. We speculate that we here preferentially detected a stable core virome, which dominated over a variable flexible virome that may have been too heterogeneous for experimental detection or was underrepresented in the databases. It will be interesting to analyze whether the enteric virome allows predictions for the clinical outcome of FMT for rCDI and other diseases such as inflammatory bowel disease or obesity.

ECMO, both of whom survived to discharge as did all babies who underwent surgical repair of the CDH. Conclusion There was an 11.1% mortality rate increase amongst the cohort studied when compared with the preceding 5 year block. A notably lower termination rate (28% vs. 50%) could possibly account for this, in addition to associated anomalies as above. Variations in management approach within the team was observed leading to the subsequent formulation of an evidence based protocol to improve care quality and future outcomes as current evidence suggests.

The gut microbiome plays a critical role in maintaining gut and metabolic health, and its composition is often altered by aging and obesity. This study aimed to investigate the protective effects of curcumin on gut dysbiosis, gut barrier integrity, and bile acid homeostasis in aged mice fed a high-fat, high-sugar diet (HFHSD). Eighteen- to twenty-one-month-old male C57BL/6 mice were divided into groups fed a normal chow diet or HFHSD, with or without curcumin supplementation (0.4% w/w) for 8 and 15 weeks. We assessed body weight, food intake, insulin sensitivity, gut microbiota composition, and gene expression in the gut and liver and performed histological analysis of gut tissues. Curcumin supplementation prevented HFHSD-induced weight gain and metabolic disturbances. In the gut, curcumin-treated mice showed a higher abundance of beneficial bacterial genera, such as Lachnospiraceae, Akkermansia, Mucispirillum, and Verrucomicrobiota, alongside a lower abundance of harmful bacterial genera like Desulfobacteria, Alistipes, and Muribaculaceae compared to control. This shift in gut microbiota was associated with improved gut integrity, as demonstrated by increased expression of the tight junction protein occludin and reduced levels of the pro-inflammatory marker interleukin-1β in the ileum. Additionally, curcumin modulated hepatic gene expression involved in bile acid homeostasis, suggesting a positive effect on liver health. Curcumin supplementation can alleviate the negative effects of aging and an HFHSD on the gut microbiome, improve gut barrier integrity, and maintain bile acid homeostasis. These findings highlight curcumin’s potential as a dietary intervention for managing obesity- and age-associated gut health issues.

The unique functionality of Akkermansia muciniphila in gut microbiota indicates it to be an indispensable microbe for human welfare. The importance of A. muciniphila lies in its potential to convert mucin into beneficial by-products, regulate intestinal homeostasis and maintain gut barrier integrity. It is also known to competitively inhibit other mucin-degrading bacteria and improve metabolic functions and immunity responses in the host. It finds a pivotal perspective in various diseases and their treatment. It has future as a promising probiotic, disease biomarker and therapeutic agent for chronic diseases. Diseaseassociated dysbiosis of A. muciniphila in the gut microbiome makes it a potential candidate as a biomarker for some diseases and can provide future theranostics by suggesting ways of diagnosis for the patients and best treatment method based on the screening results. Manipulation of A. muciniphila in gut microbiome may help in developing a novel personalized therapeutic action and can be a suitable next generation medicine. However, the actual pathway governing A. muciniphila interaction with hosts remains to be investigated. Also, due to the limited availability of products containing A. muciniphila, it is not exploited to its full potential. The present review aims at highlighting the potential of A. muciniphila in mucin degradation, contribution towards the gut health and host immunity and management of metabolic diseases such as obesity and type 2 diabetes, and respiratory diseases such as cystic fibrosis and COVID-19.

Conversion of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) to the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) is performed by a few species of intestinal bacteria in the genus Clostridium through a multistep biochemical pathway that removes a 7a-hydroxyl group. The rate-determining enzyme in this pathway is bile acid 7a-dehydratase (baiE). In this study, crystal structures of apo-BaiE and its putative product-bound [3-oxo-D 4,6lithocholyl-Coenzyme A (CoA)] complex are reported. BaiE is a trimer with a twisted a 1 b barrel fold with similarity to the Nuclear Transport Factor 2 (NTF2) superfamily. Tyr30, Asp35, and His83 form a catalytic triad that is conserved across this family. Site-directed mutagenesis of BaiE from Clostridium scindens VPI 12708 confirm that these residues are essential for catalysis and also the importance of other conserved residues, Tyr54 and Arg146, which are involved in substrate binding and affect catalytic turnover. Steady-state kinetic studies reveal that the BaiE homologs are able to turn over 3-oxo-D 4 -bile acid and CoA-conjugated 3-oxo-D 4 -bile acid substrates with comparable efficiency questioning the role of CoA-conjugation in the bile acid metabolism pathway.

Clostridium difficile is a major nosocomial pathogen responsible for close to half a million infections and 27,000 deaths annually in the U.S. Preceding antibiotic treatment is a major risk factor for C. difficile infection (CDI) leading to recognition that commensal microbes play a key role in resistance to CDI. Current antibiotic treatment of CDI is only partially successful due to a high rate of relapse. As a result, there is interest in understanding the effects of microbes on CDI susceptibility to support treatment of patients with probiotic microbes or entire microbial communities (e.g., fecal microbiota transplantation). The results reported here demonstrate that colonization with the human commensal fungus Candida albicans protects against lethal CDI in a murine model. Colonization with C. albicans did not increase the colonization resistance of the host. Rather, our findings showed that one effect of C. albicans colonization was to enhance a protective immune response. Mice pre-colonized with C. albicans expressed higher levels of IL-17A in infected tissue following C. difficile challenge compared to mice that were not colonized with C. albicans. Administration of cytokine IL-17A was demonstrated to be protective against lethal murine CDI in mice not colonized with C. albicans. C. albicans colonization was associated with changes in the abundance of some bacterial components of the gut microbiota. Therefore, C. albicans colonization altered the gut ecosystem, enhancing survival after C. difficile challenge. These findings demonstrate a new, beneficial role for C. albicans gut colonization.

Helicobacter pylori is the primary cause of peptic ulcer disease and is estimated to account for about 60% of all cases of gastric cancer, the second most common cause of cancer death worldwide. Among the H. pylori virulence factors associated with disease, in addition to the well-known cag pathogenicity island, is the BabA adhesin, an outer membrane protein that binds with high affinity to fucosylated glycans on the gastric epithelium, such as Lewis B (Le(b)) and related terminal fucose residues found on the blood group O (H antigen), A and B antigens. BabA-mediated attachment to the gastric mucosa promotes chronic inflammation and gastric pathology, which from the bacterial perspective carries both risks and benefits. We recently described modulation in expression of BabA and related outer membrane proteins that occurs during colonization of experimental animals. Here we put these findings into a broader context, and speculate on their implications for the host-pathogen relationship.

Clostridium difficile infection (CDI) is one of the most common causes of healthcare-associated infections but an even bigger problem for the aging population. Advanced age leads to higher incidence, higher mortality, and higher recurrences. In our study, recently published in the Journal of Infectious Diseases, we investigated the effect of aging on CDI using a mouse model. We were able to demonstrate that aging leads to worse clinical outcomes, as well as lead to changes in microbiota composition and lower antibody production against C. difficile toxin A, but not toxin B. An association between advanced age and lower antibody production against C. difficile is a new finding which would explain the effect of aging on CDI outcome. Vancomycin, an anti-C. difficile antibiotic, led to similar changes in antibody response, suggesting a connection between microbiome and antibody response in the context of aging, which would require a much more nuanced look at the treatment of CDI.

Enteroaggregative E. coli (EAEC) is associated with food-borne outbreaks of diarrhea and growth faltering among children in developing countries. A Shiga toxin-producing EAEC strain of serotype O104:H4 strain caused one of the largest outbreaks of a food-borne infection in Europe in 2011. The outbreak was traced to contaminated fenugreek sprouts, yet the mechanisms whereby such persistent contamination of sprouts could have occurred are not clear. We found that under ambient conditions of temperature and in minimal media, pathogenic Shiga toxin-producing EAEC O104:H4 227-11 and non-Shiga toxin-producing 042 strains both produce high levels of exopolysaccharide structures (EPS) that are released to the external milieu. The exopolysaccharide was identified as colanic acid (CA). Unexpectedly, Shiga-toxin producing EAEC strain 227-11 produced 3-6-fold higher levels of CA than the 042 strain, suggesting differential regulation of the CA in the two strains. The presence of CA was accompanied by the formation of large biofilm structures on the surface of sprouts. The wcaF-wza chromosomal locus was required for the synthesis of CA in EAEC 042. Deletion in the glycosyltransferase wcaE gene abolished the production of CA in 042, and resulted in diminished adherence to sprouts when co-cultured at ambient temperature. In conclusion, this work suggests that copious production of CA may contribute to persistence of EAEC in the environment and suggests a potential explanation for the large Shiga toxin-producing EAEC outbreak in 2011.

Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. Antibody expression and assembly were compared with CHOderived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. Susceptibility to gastric digestion was assessed in an in vitro model. Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. SIgA1 assembly appeared superior to SIgA2 in plants. Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68-61 SIgA1. The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalianlike N glycosylation. The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs.

Shigella is one of the major enteric pathogens worldwide. We present a murine model of S. flexneri infection and investigate the role of zinc deficiency (ZD). C57BL/6 mice fed either standard chow (HC) or ZD diets were pretreated with an antibiotic cocktail and received S. flexneri strain 2457T orally. Antibiotic pre-treated ZD mice showed higher S. flexneri colonization than non-treated mice. ZD mice showed persistent colonization for at least 50 days post-infection (pi). S. flexneriinfected mice showed significant weight loss, diarrhea and increased levels of fecal MPO and LCN in both HC and ZD fed mice. S. flexneri preferentially colonized the colon, caused epithelial disruption and inflammatory cell infiltrate, and promoted cytokine production which correlated with weight loss and histopathological changes. Infection with S. flexneri ΔmxiG (critical for type 3 secretion system) did not cause weight loss or diarrhea, and had decreased stool shedding duration and tissue burden. Several biochemical changes related to energy, inflammation and gut-microbial metabolism were observed. Zinc supplementation increased weight gains and reduced intestinal inflammation and stool shedding in ZD infected mice. In conclusion, young antibiotic-treated mice provide a new model of oral S. flexneri infection, with ZD promoting prolonged infection outcomes.

Enteroaggregative E. coli (EAEC) is associated with food-borne outbreaks of diarrhea and growth faltering among children in developing countries. A Shiga toxin-producing EAEC strain of serotype O104:H4 strain caused one of the largest outbreaks of a food-borne infection in Europe in 2011. The outbreak was traced to contaminated fenugreek sprouts, yet the mechanisms whereby such persistent contamination of sprouts could have occurred are not clear. We found that under ambient conditions of temperature and in minimal media, pathogenic Shiga toxin-producing EAEC O104:H4 227-11 and non-Shiga toxin-producing 042 strains both produce high levels of exopolysaccharide structures (EPS) that are released to the external milieu. The exopolysaccharide was identified as colanic acid (CA). Unexpectedly, Shiga-toxin producing EAEC strain 227-11 produced 3-6-fold higher levels of CA than the 042 strain, suggesting differential regulation of the CA in the two strains. The presence of CA was accompan...

Abbreviations: EAEC, Enteroaggregative Escherichia coli; dZD, defined zinc deficient diet; dC, defined control diet; Cftr, cystic fibrosis transmembrane regulator Enteroaggregative Escherichia coli (EAEC) is increasingly recognized as a major cause of diarrheal disease globally. In the current study, we investigated the impact of zinc deficiency on the host and pathogenesis of EAEC. Several outcomes of EAEC infection were investigated including weight loss, EAEC shedding and tissue burden, leukocyte recruitment, intestinal cytokine expression, and virulence expression of the pathogen in vivo. Mice fed a protein source defined zinc deficient diet (dZD) had an 80% reduction of serum zinc and a 50% reduction of zinc in luminal contents of the bowel compared to mice fed a protein source defined control diet (dC). When challenged with EAEC, dZD mice had significantly greater weight loss, stool shedding, mucus production, and, most notably, diarrhea compared to dC mice. Zinc deficient mice had reduced infiltration of leukocytes into the ileum in response to infection suggesting an impaired immune response. Interestingly, expression of several EAEC virulence factors were increased in luminal contents of dZD mice. These data show a dual effect of dietary zinc in benefitting the host while impairing virulence of the pathogen. The study demonstrates the critical importance of zinc and may help elucidate the benefits of zinc supplementation in cases of childhood diarrhea and malnutrition.

Impaired gut barrier function has been reported in a wide range of diseases and syndromes and in some functional gastrointestinal disorders. In addition, there is increasing evidence that suggests the gut microbiota tightly regulates gut barrier function and recent studies demonstrate that probiotic bacteria can enhance barrier integrity. Here, we aimed to investigate the effects of Lactobacillus rhamnosus CNCM I-3690 on intestinal barrier function. In vitro results using a Caco-2 monolayer cells stimulated with TNF-α confirmed the anti-inflammatory nature of the strain CNCM I-3690 and pointed out a putative role for the protection of the epithelial function. Next, we tested the protective effects of L. rhamnosus CNCM I-3690 in a mouse model of increased colonic permeability. Most importantly, we compared its performance to that of the well-known beneficial human commensal bacterium Faecalibacterium prauznitzii A2-165. Increased colonic permeability was normalized by both strains to...

The methanogenic community throughout the gastrointestinal tract (GIT) of pre-weaned calves has not been well studied. The current study firstly investigated the distribution and composition of the methanogenic community in the rumen, ileum, and colon of 3-4 week-old milk-fed dairy calves (n D 4) using 16S rRNA gene clone library analysis. The occurrence of methanogens in the GIT of pre-weaned calves was further validated by using PCR-denaturing gradient gel electrophoresis (PCR-DGGE), and quantitative real-time PCR (qPCR) was applied to quantify the methanogenic community in the rumen, jejunum, ileum, cecum, colon and rectum of 8 3-4 week old animals. Both cloning libraries and PCR-DGGE revealed that phylotypes close to Methanobrevibacter were the main taxon along the GIT in pre-weaned sucking calves. The composition and abundance of methanogens varied significantly among individual animals, suggesting that host conditions may influence the composition of the symbiotic microbiota. Segregation of methanogenic communities throughout the GIT was also observed within individual animals, suggesting possible functional differences among methanogens residing in different GIT regions. This is the first study to analyze methanogenic communities throughout the GIT of milk-fed newborn dairy calves and reveal both their diversity and abundance. The identification of methanogens in the lower GIT of pre-weaned dairy calves warrants further investigation to better define methanogen roles in GIT function and their impact on host metabolism and health.

The faecal microbiota, an intricate and diverse community of bacteria found in the gastrointestinal tract, is vital to human well-being. Microbes of this kind, which include fungi, bacteria, viruses, and archaea, support a number of essential functions, including as immune system regulation, vitamin synthesis, and digestion. The faecal microbiota is implicated in various illnesses and is essential to maintaining health. The advancements in bioinformatics and sequencing technology have allowed for a greater understanding of its composition, variety, and functionality. Firmicutes and Bacteroidetes make up the bulk of the bacteria in the gut microbiota, with Actinobacteria, Proteobacteria, Verrucomicrobia, and Fusobacteria following in order of abundance. These bacterial populations are influenced by age, diet, genetics, antibiotic use, and environment; higher diversity is typically associated with better health. Short-chain fatty acids (SCFAs), are produced when firmicutes, such as Lactobacillus and Clostridium, digest food fibers. SCFAs are critical for gut health. Prevotella and other members of the Bacteroidetes family are essential for the breakdown of complex carbohydrates. Similar to Bifidobacterium, actinobacteria are good for gut health, especially in young children. Although they are less common, proteobacteria include dangerous species like Salmonella and Escherichia, while verrucomicrobia-most notably, Akkermansia muciniphila-help to maintain a healthy gut lining and have antiinflammatory qualities. The gut microbiota is the target of several therapeutic interventions, including antibiotic stewardship, faecal microbiota transplantation (FMT), probiotics, and prebiotics. Prebiotics and probiotics have the power to improve health outcomes by re-establishing microbial balance. The gut microbiota may be precisely altered by novel therapies such as nextgeneration probiotics, synbiotics, and drugs that target the microbiome. The gut microbiota-brain link, the microbiome-gut-brain axis, and the role of microorganisms in cancer treatment will be the focus of future research. The effectiveness of medicines targeting the microbiota will be improved by personalized medicine approaches that take individual microbial patterns into account.

Background Escherichia coli strains harbouring the pks island ( pks+ E. coli) are often seen in human colorectal tumours and have a carcinogenic effect independent of inflammation in an AOM/IL-10 -/-(azoxymethane/ interleukin) mouse model. Objective To investigate the mechanism sustaining pks+ E. coli-induced carcinogenesis. Method Underlying cell processes were investigated in vitro and in vivo (xenograft model) using intestinal epithelial cells infected by pks+ E. coli or by an isogenic mutant defective for pks ( pks-E. coli). The results were supported by data obtained from an AOM/DSS (azoxymethane/dextran sodium sulphate) colon cancer mouse model and from human colon cancer biopsy specimens colonised by pks+ E. coli or pks-E. coli. Results Colibactin-producing E. coli enhanced tumour growth in both xenograft and AOM/DSS models. Growth was sustained by cellular senescence (a direct consequence of small ubiquitin-like modifier (SUMO)conjugated p53 accumulation), which was accompanied by the production of hepatocyte growth factor (HGF). The underlying mechanisms involve microRNA-20a-5p, which targets SENP1, a key protein regulating p53 deSUMOylation. These results are consistent with the expression of SENP1, microRNA-20a-5p, HGF and phosphorylation of HGF receptor found in human and mouse colon cancers colonised by pks+ E. coli. Conclusion These data reveal a new paradigm for carcinogenesis, in which colibactin-induced senescence has an important role.

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichacea...

Background: Klebsiella pneumoniae (hereafter, Kp) is a major public health threat responsible for high levels of multidrug resistant (MDR) human infections. Besides, Kp also causes severe infections in the community, especially in Asia and Africa. Although most Kp infections are caused by endogenous intestinal carriage, little is known about the prevalence and microbiological characteristics of Kp in asymptomatic human carriage, and attached risk factors including environmental sources exposure. Methods: Here, 911 pregnant women from communities in Madagascar, Cambodia, and Senegal were screened for gut colonization by Kp. Characteristics of Kp strains (antimicrobial susceptibility, genomic diversity, virulence, and resistance genes) were defined, and associated risk factors were investigated. Results: Kp carriage rate was 55.9%, and Kp populations were highly heterogeneous (6 phylogroups, 325 sequence types, Simpson index 99.6%). One third of Kp isolates had acquired antimicrobial resistance genes. MDR-Kp (11.7% to 39.7%) and extended spectrum beta-lactamase (ESBL)-producing Kp (0.7% to 14.7%) varied among countries. Isolates with virulence genes were detected (14.5%). Environmental exposure factors including food, animal contacts, or hospitalization of household members were associated with carriage of Kp, antimicrobial resistance and hypervirulence. However, risk factors were countryspecific and Kp subpopulation-specific. Conclusion: This large-scale multicenter study uncovers the huge diversity of Kp in human gut carriage, demonstrates that antimicrobial resistance is widespread in communities of three lowincome countries, and underlines the challenges posed by Kp colonization to the control of antimicrobial resistance.

The protective effect of Lactobacillus rhamnosus 231 (Lr 231) against potent carcinogen N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG) in the rat model is studied. Daily feeding with Lr 231 improved the body weight of male Wistar rats compared with control groups. Fecal azoreductase (p , 0.001) and nitroreductase (p , 0.01) enzyme activity decreased significantly in Lr 231 group in comparison with control groups that received only phosphate buffer or MNNG. Oral administration of MNNG led to a significant increase in Glutathione transferase (GST) while Glutathione reductase (GSH) showed decreased activity. Conversely, feeding Lr 231 showed significantly increased GSH and decreased GST activity in comparison to the MNNG group, emphasizing the protection provided by Lr 231 against MNNG. Histopathological analysis of liver, spleen and colon showed decreased signs of inflammation in the Lr 231 group. The present study highlights that inclusion of active Lr 231 in regular diets could be used to prevent MNNG induced colon carcinoma.

The search for biological markers that can be reliably linked to aggression and antisocial behavior has been central to work of biological criminology. One such marker, uric acid, has long-since been suspected to play a causative role in promoting anger, irritability, aggression, and violence. Here in this perspective article, we revisit some of the historical interest in uric acid as a compound relevant to brain and behavior, and reflect these early accounts off emergent scientific research. Advances in brain sciences, including neuropsychiatry and neuromicrobiology, have allowed for a more sophisticated understanding of potential mechanistic pathways linking uric acid with cognition and behavior. The updated science suggests that some of the early ideas surrounding uric acid and criminology had credibility. The available research strongly suggests that uric acid, as a potential biomarker of risk, is worthy of further research and close scrutiny. Informed by emergent gut-brain-microbiome research, we argue that certain aspects of early-to-mid 20 th century biological criminology were prematurely abandoned. From a neurolaw perspective, further advances surrounding uric acid, and other gut-brain biomarkers, can aid in shaping more humane, scientifically grounded, policies that recognize the interplay between biology and environment.

This review examines the intricate relationship between the gut microbiome, gastrointestinal, and mental health, mediated by the gut-brain axis. A balanced gut microbiome, characterized by diverse microbiota, optimal composition, healthy motility, robust barrier integrity, and appropriate enzymatic activity, is crucial for both digestive and neurological well-being. Conversely, gut dysbiosis, increased intestinal permeability, and inflammation can disrupt gut-brain communication, contributing to digestive disorders, autoimmune diseases, and neuropsychological manifestations such as anxiety, depression, and cognitive decline. While modern medical interventions form the cornerstone of treatment, integrative approaches, including dietary modifications, probiotic and prebiotic supplementation, lifestyle adjustments, nutritional therapies, and psychological interventions, can serve as valuable complements. Furthermore, certain herbal remedies may offer adjunctive support. Strategies for maintaining a healthy gut microbiome, such as a balanced diet, regular physical activity, adequate hydration, sufficient sleep, and effective stress management, are essential for promoting optimal gut-brain communication and overall well-being. Gradual lifestyle modifications, prioritizing stress reduction, physical activity, and a natural diet can facilitate the development of a healthy gut microbiome, leading to improvements in both gastrointestinal and mental health.

Excessive alcohol intake can alter the gut microbiota, which may underlie the pathophysiology of alcohol-related diseases. We examined gut microbiota composition and functions in patients with alcohol overconsumption for >10 years, compared to a control group of patients with a history of no or low alcohol intake. Faecal microbiota composition was assessed by 16S rRNA sequencing. Gut microbiota functions were evaluated by quantification of short-chain fatty acids (SCFAs) and predictive metagenome profiling (PICRUSt). Twenty-four patients, mean age 64.8 years (19 males), with alcohol overconsumption, and 18 control patients, mean age 58.2 years (14 males) were included. The two groups were comparable regarding basic clinical variables. Nutritional assessment revealed lower total score on the screening tool Mini Nutritional Assessment, lower muscle mass as assessed by handgrip strength, and lower plasma vitamin C levels in the alcohol overconsumption group. Bacteria from phylum Proteobacteria were found in higher relative abundance, while bacteria from genus Faecalibacterium were found in lower relative abundance in the group of alcohol overconsumers. The group also had higher levels of the genera Sutterella, Holdemania and Clostridium, and lower concentration and percentage of butyric acid. When applying PICRUSt to predict the metagenomic composition, we found that genes related to invasion of epithelial cells were more common in the group of alcohol overconsumers. We conclude that gut microbiota composition and functions in patients with alcohol overconsumption differ from patients with low consumption of alcohol, and seem to be skewed into a putative pro-inflammatory direction.

In humans, sleeping sickness (i.e. Human African Trypanosomiasis) is caused by the protozoan parasites Trypanosoma brucei gambiense (Tbg) in West and Central Africa, and T. b. rhodesiense in East Africa. We previously showed in vitro that Tbg is able to excrete/secrete a large number of proteins, including Translationally Controlled Tumor Protein (TCTP). Moreover, the tctp gene was described previously to be expressed in Tbg-infected flies. Aside from its involvement in diverse cellular processes, we have investigated a possible alternative role within the interactions occurring between the trypanosome parasite, its tsetse fly vector, and the associated midgut bacteria. In this context, the Tbg tctp gene was synthesized and cloned into the baculovirus vector pAcGHLT-A, and the corresponding protein was produced using the baculovirus Spodoptera frugicola (strain 9) / insect cell system. The purified recombinant protein rTbgTCTP was incubated together with bacteria isolated from the gut of tsetse flies, and was shown to bind to 24 out of the 39 tested bacteria strains belonging to several genera. Furthermore, it was shown to affect the growth of the majority of these bacteria, especially when cultivated under microaerobiosis and anaerobiosis. Finally, we discuss the potential for TCTP to modulate the fly microbiome composition toward favoring trypanosome survival.

Prior research suggests probiotic consumption provides many health benefits to the consumer. Evidence from recent studies indicates that probiotics may alter mood via the gut-brain axis. The alterations in mood shown in previous research are attributed to alterations in GABAA receptor subunit expression. GABA is the primary inhibitory neurotransmitter, and manipulation of ion flow through GABA receptors is a reliable way to manipulate anxiety. The goal of the current study was to investigate how daily administration of probiotics affected the expression of anxiety behaviors in the treated animals. We hypothesized that daily administration of Lactobacillus reuteri would result in decreased expression of anxiety behaviors. Newly weaned animals were fed daily either a 10% sucrose sterile broth solution, or a 10% sucrose broth solution containing L. reuteri (10 9 colony forming units per dose), until all animals were 70 days of age. Following the administration period, animals were test...

Helicobacter pylori strains expressing the virulence factor cytotoxinassociated gene A (CagA) stimulate increased levels of spermine oxidase (SMO) in gastric epithelial cells, while cagA -strains did not. SMO catabolizes the polyamine spermine and produces H 2 O 2 that results in both apoptosis and DNA damage. Exogenous overexpression of CagA confirmed these findings, and knockdown or inhibition of SMO blocked CagA-mediated apoptosis and DNA damage. The strong association of SMO, apoptosis, and DNA damage was also demonstrated in humans infected with cagA + , but not cagA -strains. In infected gerbils and mice, DNA damage was CagA-dependent and only present in epithelial cells that expressed SMO. We also discovered SMO high gastric epithelial cells from infected animals with dysplasia that are resistant to apoptosis despite high levels of DNA damage. Inhibition of polyamine synthesis or SMO could abrogate the development of this cell population that may represent precursors for neoplastic transformation.