Gastrointestinal microbiome and Helicobacter pylori:Eradicate,leave it as it is,or take a personalized benefit-risk approach?

Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.However,H.pylori can also be regarded as a commensal symbiont.Unlike other pathogenic/opportunistic bacteria,H.pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance.Fucosylated gastric mucin glycans,which are an important part of the innate and adaptive immune system,mediate the adhesion of H.pylori to the surface of the gastric epithelium,contributing to successful colonization.H.pylori may have beneficial effects on the host by regulating gastrointestinal(GI)microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease.The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H.pylori.The inverse association between H.pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota.Eradication of H.pylori can cause various adverse effects and alter the GI microbiota,leading to short-term or long-term dysbiosis.Overall,studies have shown that gastric Actinobacteria decrease after H.pylori eradication,Proteobacteria increase during short-term follow-up and then return to baseline levels,and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up.Various gastric mucosal bacteria(Actinomyces,Granulicatella,Parvimonas,Peptostreptococcus,Prevotella,Rothia,Streptococcus,Rhodococcus,and Lactobacillus)may contribute to precancerous gastric lesions and cancer itself after H.pylori eradication.H.pylori eradication can also lead to dysbiosis of the gut microbiota,with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria.The increase in gut Proteobacteria may contribute to adverse effects during and after eradication.The decrease in Actinobacteria,which are pivotal in the maintenance of gut homeostasis,can persist for>6 mo after H.pylori eradication.Furthermore,H.pylori eradication can alter the metabolism of gastric and intestinal bacteria.Given the available data,eradication cannot be an unconditional recommendation in every case of H.pylori infection,and the decision to eradicate H.pylori should be based on an assessment of the benefit-risk ratio for the individual patient.Thus,the current guidelines based on the unconditional"test-and-treat"strategy should be revised.The most cautious and careful approach should be taken in elderly patients with multiple eradication failures since repeated eradication can cause antibiotic-associated diarrhea,including severe Clostridioides difficile-associated diarrhea and colitis and antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca.Furthermore,since eradication therapy with antibiotics and proton pump inhibitors can lead to serious adverse effects and/or dysbiosis of the GI microbiota,supplementation of probiotics,prebiotics,and microbial metabolites(e.g.,butyrate+inulin)should be considered to decrease the negative effects of eradication.

Potential of a fucoidan-rich Ascophyllum nodosum extract to reduce Salmonella shedding and improve gastrointestinal health in weaned pigs naturally infected with Salmonella

Background:Dietary supplementation with a fucoidan-rich Ascophyllum nodosum extract(ANE),possessing an in vitro anti-Salmonella Typhimurium activity could be a promising on-farm strategy to control Salmonella infection in pigs.The objectives of this study were to:1)evaluate the anti-S.Typhimurium activity of ANE(containing 46.6%fucoidan,18.6%laminarin,10.7%mannitol,4.6%alginate)in vitro,and;2)compare the effects of dietary supplementation with ANE and Zinc oxide(ZnO)on growth performance,Salmonella shedding and selected gut parameters in naturally infected pigs.This was established post-weaning(newly weaned pig experiment)and following regrouping of post-weaned pigs and experimental re-infection with S.Typhimurium(challenge experiment).Results:In the in vitro assay,increasing ANE concentrations led to a linear reduction in S.Typhimurium counts(P<0.05).In the newly weaned pig experiment(12 replicates/treatment),high ANE supplementation increased gain to feed ratio,similar to ZnO supplementation,and reduced faecal Salmonella counts on d 21 compared to the low ANE and control groups(P<0.05).The challenge experiment included thirty-six pigs from the previous experiment that remained on their original dietary treatments(control and high ANE groups with the latter being renamed to ANE group)apart from the ZnO group which transitioned onto a control diet on d 21(ZnO-residual group).These dietary treatments had no effect on performance,faecal scores,Salmonella shedding or colonic and caecal Salmonella counts(P>0.05).ANE supplementation decreased the Enterobacteriaceae counts compared to the control.Enterobacteriaceae counts were also reduced in the ZnO-residual group compared to the control(P<0.05).ANE supplementation decreased the expression of interleukin 22 and transforming growth factor beta 1 in the ileum compared to the control(P<0.05).Conclusions:ANE supplementation was associated with some beneficial changes in the composition of the colonic microbiota,Salmonella shedding,and the expression of inflammatory genes associated with persistent Salmonella infection.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Helicobacter pylori eradication:Exploring its impacts on the gastric mucosa

Helicobacter pylori(H.pylori)infects approximately 50%of all humans globally.Persistent H.pylori infection causes multiple gastric and extragastric diseases,indicating the importance of early diagnosis and timely treatment.H.pylori eradication produces dramatic changes in the gastric mucosa,resulting in restored function.Consequently,to better understand the importance of H.pylori eradication and clarify the subsequent recovery of gastric mucosal functions after eradication,we summarize histological,endoscopic,and gastric microbiota changes to assess the therapeutic effects on the gastric mucosa.

The effects of dietary supplementation with mushroom or selenium enriched mushroom powders on the growth performance and intestinal health of post-weaned pigs

Background There is an urgent need to identify natural bioactive compounds that can enhance gastrointestinal health and promote pig growth performance in the absence of pharmacological levels of zinc oxide(ZnO).The objectives of this study were to:1)compare the effects of mushroom powder supplemented with inorganic selenium(inSeMP)to mushroom powder enriched with organic selenium(orgSeMP)to pharmacological levels of ZnO on growth performance and faecal scores(FS)for the first 21 d post-weaning(Period 1);and 2)compare the molecular and microbial effects of inSeMP and orgSeMP in these pigs on d 39 post-weaning(Period 2).Methods In Period 1,pigs(3 pigs/pen;8 pens/treatment)were assigned to:(1)basal diet(control);(2)basal diet+zinc oxide(ZnO)(3100 mg/kg d 1–14,1550 mg/kg d 15–21);(3)basal diet+mushroom powder supplemented with inorganic selenium(inSeMP)containing selenium(selenite)content of 0.3 mg/kg feed;(4)basal diet+mushroom powder enriched with organic selenium(orgSeMP)containing selenium(selenocysteine)content of 0.3 mg/kg feed.Mushroom powders were included at 6.5 g/kg of feed.Results In Period 1,there was no effect of diets on average daily gain(ADG)and gain:feed(G:F)ratio(P>0.05).The orgSeMP supplemented pigs had a lower average daily feed intake(ADFI)compared to all other groups(P<0.05).The ZnO supplemented pigs had reduced FS compared to the basal and mushroom group,while the orgSeMP supplemented pigs had lower FS compared to the basal group during the 21 d experimental period(P<0.05).In Period 2,there was no effect of diets on ADFI,ADG and G:F ratio(P>0.05).The orgSeMP supplementation increased the caecal abundance of bacterial members of the Firmicutes and Bacteroidetes phylum,including Lactobacillus,Agathobacter,Roseburia,and Prevotella and decreased the abundance of Sporobacter compared to the basal group,while inSeMP increased the caecal abundance of Prevotella and decreased the caecal abundance of Sporobacter compared to the basal group(P<0.05).Dietary supplementation with inSeMP increased expression of TLR4 and anti-inflammatory cytokine gene IL10 and decreased nutrient transporter gene FABP2 compared to the orgSeMP group(P<0.05).Conclusion OrgSeMP is a novel and sustainable way to incorporate selenium andβ-glucans into the diet of weaned pigs whilst improving FS and modulating the caecal microbiota.

Comparison of bacterial quantities in left and right colon biopsies and faeces

AIM:To compare quantities of predominant and pathogenic bacteria in mucosal and faecal samples.METHODS:Twenty patients undergoing diagnostic colonoscopy with endoscopically and histologically normal mucosa were recruited to the study,14 subjects of which also supplied faecal(F) samples between 15 d to 105 d post colonoscopy.Mucosal biopsies were taken from each subject from the midportion of the ascending colon(right side samples,RM) and the sigmoid(left side samples,LM).Predominant intestinal and mucosal bacteria including clostridial 16S rRNA gene clusters Ⅳ and ⅩⅣab,Bacteroidetes,Enterobacteriaceae,Bifidobacterium spp.,Akkermansia muciniphila(A.muciniphila),Veillonella spp.,Collinsella spp.,Faecalibacterium prausnitzii(F.prausnitzii) and putative pathogens such asEscherichia coli(E.coli),Clostridium difficile(C.difficile),Helicobacter pylori(H.pylori) and Staphylococcus aureus(S.aureus) were analysed by quantitative polymerase chain reaction(qPCR).Host DNA was quantified from the mucosal samples with human glyceraldehyde 3-phosphate dehydrogenase gene targeting qPCR.Paired t tests and the Pearson correlation were applied for statistical analysis.RESULTS:The most prominent bacterial groups were clostridial groups Ⅳ and ⅩⅣa+b andBacteroidetes and bacterial species F.prausnitzii in both sample types.H.pylori and S.aureus were not detected and C.difficile was detected in only one mucosal sample and three faecal samples.E.coli was detected in less than half of the mucosal samples at both sites,but was present in all faecal samples.All detected bacteria,except Enterobacteriaceae,were present at higher levels in the faeces than in the mucosa,but the different locations in the colon presented comparable quantities(RM,LM and F followed byP 1 for RMvs F,P 2 for LMvs F andP 3 for RM vs LM:4.17 ± 0.60 log 10 /g,4.16 ± 0.56 log 10 /g,5.88 ± 1.92 log 10 /g,P 1 = 0.011,P 2 = 0.0069,P 3 = 0.9778 forA.muciniphila;6.25 ± 1.3 log 10 /g,6.09 ± 0.81 log 10 /g,8.84 ± 1.38 log 10 /g,P 1 < 0.0001,P 2 = 0.0002,P 3 = 0.6893 forBacteroidetes;5.27 ± 1.68 log 10 /g,5.38 ± 2.06 log 10 /g,8.20 ± 1.14 log 10 /g,P 1 < 0.0001,P 2 ≤ 0.0001,P 3 = 0.7535 forBifidobacterium spp.;6.44 ± 1.15 log 10 /g,6.07 ±1.45 log 10 /g,9.74 ±1.13 log 10 /g,P 1 < 0.0001,P 2 ≤ 0.0001,P 3 = 0.637 forClostridium cluster Ⅳ;6.65 ± 1.23 log 10 /g,6.57 ± 1.52 log 10 /g,9.13 ± 0.96 log 10 /g,P 1 < 0.0001,P 2 ≤ 0.0001,P 3 = 0.9317 forClostridium cluster ⅩⅣa;4.57 ± 1.44 log10/g,4.63 ± 1.34 log10/g,7.05 ± 2.48 log 10 /g,P 1 = 0.012,P 2 = 0.0357,P 3 = 0.7973 for Collinsella spp.;7.66 ± 1.50 log 10 /g,7.60 ± 1.05 log 10 /g,10.02 ± 2.02 log 10 /g,P 1 ≤ 0.0001,P 2 = 0.0013,P 3 = 0.9919 forF.prausnitzsii;6.17 ± 1.3 log 10 /g,5.85 ± 0.93 log 10 /g,7.25 ± 1.01 log 10 /g,P 1 = 0.0243,P 2 = 0.0319,P 3 = 0.6982 for Veillonella spp.;4.68 ± 1.21 log 10 /g,4.71 ± 0.83 log 10 /g,5.70 ± 2.00 log 10 /g,P 1 = 0.1927,P 2 = 0.0605,P 3 = 0.6476 forEnterobacteriaceae).TheBifidobacterium spp.counts correlated significantly between mucosal sites and mucosal and faecal samples(Pearson correlation coefficients 0.62,P = 0.040 and 0.81,P = 0.005 between the right mucosal sample and faeces and the left mucosal sample and faeces,respectively).CONCLUSION:Non-invasive faecal samples do not reflect bacterial counts on the mucosa at the individual level,except for bifidobacteria often analysed in probiotic intervention studies.

Microbial,immune and antioxidant responses of Nile tilapia with dietary nano-curcumin supplements under chronic low temperatures

A 56-day feeding period was performed to investigate the possible impacts of dietary nano curcumin(0,50,100,150,and 200 ppm)on the growth,nutrient utilization,non-specific immune parameters,antioxidants in Nile tilapia under chronic low temperature(21.02±0.11◦C).Fishes(n=225;Initial weight=4.39±0.08 g/fish)were randomly stocked at 15 fish/tank for five experimental groups in triplicates.Under low-temperature circumstances,dietary curcumin in nano form showed no notable alteration in growth variable,nutrient efficiency,digestive enzymes efficiency,biometric indices,survival rates,and hematological components.Meanwhile,the serum of fishes with nano curcumin diets under low-temperature stress displayed higher total protein as well as lower glucose,cortisol,and total cholesterol compared with the control group.Moreover,fish fed nano curcumin diets displayed higher lysozyme and bactericidal activities compared to the control group and the best performance was found at dietary nano curcumin level of≥100 ppm.Also,groups fed the basal diet demonstrated the poorest antioxidant capacity,and the best superoxide dismutase(SOD)and glutathione peroxidase(GPx)existed in fish with nano curcumin diets while the best catalase(CAT)efficiency occurred at higher nano curcumin levels≥100 ppm.In addition,higher counts of intestinal microbiota in terms of total bacterial count(TBC),total yeast and molds count(TYMC),and coliform were noticed in fish consumed the basal diet compared to groups fed on nano curcumin diets.In conclusion,incorporating nano curcumin at a level of≥100 mg/kg diet(particularly at 150 mg/kg)improved a non-specific immune response,antioxidant,and healthier gastrointestinal microbiota in Nile tilapia under chronic low-temperature stress.

Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism

Autism spectrum disorder(ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. ASD is characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. Recent reviews have provided further insight into the genetic/genomic basis of ASD. It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones.

Fecal microbial diversity and putative function in captive western lowland gorillas(Gorilla gorilla gorilla),common chimpanzees(Pan troglodytes),Hamadryas baboons(Papio hamadryas)and binturongs(Arctictis binturong)

Microbial populations in the gastrointestinal tract contribute to host health and nutrition.Although gut microbial ecology is well studied in livestock and domestic animals,little is known of the endogenous populations inhab­iting primates or carnivora.We characterized microbial populations in fecal cultures from gorillas(Gorilla go­rilla gorilla),common chimpanzees(Pan troglodytes),Hamadryas baboons(Papio hamadryas)and binturongs(Arctictis binturong)to compare the microbiomes associated with different gastrointestinal morphologies and different omnivorous feeding strategies.Each species was fed a distinct standardized diet for 2 weeks prior to fecal collection.All diets were formulated to reflect the species’feeding strategies in situ.Fresh fecal samples were pooled within species and used to inoculate in vitro batch cultures.Acetate,propionate,butyrate and val­erate were measured after 24 h of incubation.Eubacterial DNA was extracted from individual fecal samples,pooled,and the cpn60 gene region was amplified and then sequenced to identify the major eubacterial constit­uents associated with each host species.Short chain fatty acids(P<0.001)and methane(P<0.001)were sig­nificantly different across species.Eubacterial profiles were consistent with fermentation data and suggest an in­crease in diversity with dietary fiber.