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Background: Pregnancy is a vulnerable time where the lives of mother and baby are affected by diet, especially high-risk pregnancies in women with inflammatory bowel disease (IBD). Limited research has examined diet during pregnancy with IBD. Aims: Describe and compare the diet quality of pregnant women with and without IBD, and examine associations between dietary intake and guidelines during pregnancy. Methods: Three 24 h recalls were utilized to assess the diets of pregnant women with IBD (n = 88) and without IBD (n = 82) during 27–29 weeks of gestation. A customized frequency questionnaire was also administered to measure pre- and probiotic foods. Results: Zinc intake (p = 0.02), animal protein (g) (p = 0.03), and ounce equivalents of whole grains (p = 0.03) were significantly higher in the healthy control (HC) group than the IBD group. Nutrients of concern with no significant differences between groups included iron (3% IBD and 2% HC met the goals), saturated fat (only 1% of both groups met the goals), choline (23% IBD and 21% HC met the goals), magnesium (38% IBD and 35% HC met the goals), calcium (48% IBD and 60% HC met the goals), and water intake (49% IBD and 48% HC met the goals). Conclusions: Most pregnant women in this cohort fell short of the dietary nutrients recommended in pregnancy, especially concerning for women with IBD.

The microbiome inherited at birth exerts marked effects on immune programming with long-term health consequences. Here, we demonstrated that the gut, vaginal, and oral microbial diversity of pregnant women with SARS-CoV-2 infection is reduced, and women with early infections exhibit a different vaginal microbiota composition compared to healthy controls at the time of delivery. Accordingly, infants born to pregnant women with early SARS-CoV-2 infection exhibit a unique oral microbiota dominated byStreptococcusspecies. Together, we demonstrated that SARS-CoV-2 infections during pregnancy, particularly early infections, are associated with lasting changes in the microbiome of pregnant women compromising the initial microbial seed of their infant. Our results highlight the importance of further exploring the impact of SARS-CoV-2 on the infant’s microbiome-dependent immune programming.One Sentence SummaryPregnant patients with SARS-CoV-2 infection early in pregnancy and with active infection exhibit an altered vaginal and oral microbiota that is passed on to infants.

Background Evaluating the performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays and clearly articulating the utility of selected antigens, isotypes, and thresholds is crucial to understanding the prevalence of infection within selected communities. Methods This cross-sectional study, implemented in 2020, screened PCR–confirmed coronavirus disease 2019 patients (n = 86), banked prepandemic and negative samples (n = 96), healthcare workers and family members (n = 552), and university employees (n = 327) for anti–SARS-CoV-2 receptor-binding domain, trimeric spike protein, and nucleocapsid protein immunoglobulin (Ig)G and IgA antibodies with a laboratory-developed enzyme-linked immunosorbent assay and tested how antigen, isotype and threshold choices affected the seroprevalence outcomes. The following threshold methods were evaluated: (i) mean + 3 standard deviations of the negative controls; (ii) 100% specificity for each antigen-isotype combination; and (iii) the maximal Youden index. Results We found vastly different seroprevalence estimates depending on selected antigens and isotypes and the applied threshold method, ranging from 0.0% to 85.4%. Subsequently, we maximized specificity and reported a seroprevalence, based on more than one antigen, ranging from 9.3% to 25.9%. Conclusions This study revealed the importance of evaluating serosurvey tools for antigen-, isotype-, and threshold-specific sensitivity and specificity, to interpret qualitative serosurvey outcomes reliably and consistently across studies.

Inflammatory bowel diseases (IBD), namely, Crohn's disease (CD) and ulcerative colitis (UC), are lifelong and incurable chronic inflammatory diseases affecting 6.8 million people worldwide. By 2030, the prevalence of IBD is estimated to reach 1% of the population in Western countries, and thus there is an urgent need to develop effective therapies to reduce the burden of this disease. Microbiome dysbiosis is at the heart of the IBD pathophysiology, and current research and development efforts for IBD treatments have been focused on gut microbiome regulation. Diet can shape the intestinal microbiome. Diet is also preferred over medication, is safe, and has been proven to be an effective strategy for the management of IBD. Therefore, although often overlooked, dietary interventions targeting the microbiome represent ideal treatments for IBD. Here, I summarize the latest research on diet as a treatment for IBD from infancy to adulthood, compile evidence of the mechanisms of action behind diet as treatment, and, lastly, provide insights into future research focusing on culturally tailored diets for ethnic minority groups with increased incidence of IBD yet underrepresented in nutrition research.

Shigella spp. are highly adapted pathogens that cause bacillary dysentery in human and nonhuman primates. An unusual feature of Shigella pathogenesis is that this organism invades the colonic epithelia from the basolateral pole. Therefore, it has evolved the ability to disrupt the intestinal epithelial barrier to reach the basolateral surface. We have shown previously that the secreted serine protease A (SepA), which belongs to the family of serine protease autotransporters of Enterobacteriaceae, is responsible for the initial destabilization of the intestinal epithelial barrier that facilitates Shigella invasion. However, the mechanisms used by SepA to regulate this process remain unknown. To investigate the protein targets cleaved by SepA in the intestinal epithelium, we incubated a sample of homogenized human colon with purified SepA or with a catalytically inactive mutant of this protease. We discovered that SepA targets an array of 18 different proteins, including alpha-1 antitrypsin (AAT), a major circulating serine proteinase inhibitor in humans. In contrast to other serine proteases, SepA cleaved AAT without forming an inhibiting complex, which resulted in the generation of a neutrophil chemoattractant. We demonstrated that the products of the AAT-SepA reaction induce a mild but significant increase in neutrophil transepithelial migration in vitro. Moreover, the presence of AAT during Shigella infection stimulated neutrophil migration and dramatically enhanced the number of bacteria invading the intestinal epithelium in a SepA-dependent manner. We conclude that by cleaving AAT, SepA releases a chemoattractant that promotes neutrophil migration, which in turn disrupts the intestinal epithelial barrier to enable Shigella invasion. IMPORTANCE Shigella is the second leading cause of diarrheal death globally. In this study, we identified the host protein targets of SepA, Shigella’s major protein secreted in culture. We demonstrated that by cleaving AAT, a serine protease inhibitor important to protect surrounding tissue at inflammatory sites, SepA releases a neutrophil chemoattractant that enhances Shigella invasion. Moreover, SepA degraded AAT without becoming inhibited by the cleaved product, and SepA catalytic activity was enhanced at higher concentrations of AAT. Activation of SepA by an excess of AAT may be physiologically relevant at the early stages of Shigella infection, when the amount of synthesized SepA is very low compared to the concentration of AAT in the intestinal lumen. This observation may also help to explain the adeptness of Shigella infectivity at low dose, despite the requirement of reaching the basolateral side to invade and colonize the colonic epithelium.

Shigella spp. are highly adapted pathogens that cause bacillary dysentery in human and nonhuman primates. An unusual feature of Shigella pathogenesis is that this organism invades the colonic epithelia from the basolateral pole. Therefore, it has evolved the ability to disrupt the intestinal epithelial barrier to reach the basolateral surface. We have shown previously that the secreted serine protease A (SepA), which belongs to the family of serine protease autotransporters of Enterobacteriaceae, is responsible for the initial destabilization of the intestinal epithelial barrier that facilitates Shigella invasion. However, the mechanisms used by SepA to regulate this process remain unknown. To investigate the protein targets cleaved by SepA in the intestinal epithelium, we incubated a sample of homogenized human colon with purified SepA or with a catalytically inactive mutant of this protease. We discovered that SepA targets an array of 18 different proteins, including alpha-1 antitrypsin (AAT), a major circulating serine proteinase inhibitor in humans. In contrast to other serine proteases, SepA cleaved AAT without forming an inhibiting complex, which resulted in the generation of a neutrophil chemoattractant. We demonstrated that the products of the AAT-SepA reaction induce a mild but significant increase in neutrophil transepithelial migration in vitro. Moreover, the presence of AAT during Shigella infection stimulated neutrophil migration and dramatically enhanced the number of bacteria invading the intestinal epithelium in a SepA-dependent manner. We conclude that by cleaving AAT, SepA releases a chemoattractant that promotes neutrophil migration, which in turn disrupts the intestinal epithelial barrier to enable Shigella invasion.

Diet is a modifiable, non-invasive, inexpensive behavior that is crucial in shaping the intestinal microbiome. A microbiome “imbalance” or dysbiosis in inflammatory bowel disease (IBD) is linked to inflammation. Here, we aim to define the impact of specific foods on bacterial species commonly depleted in patients with IBD to better inform dietary treatment. We performed a single-arm, pre-post intervention trial. After a baseline period, a dietary intervention with the IBD-Anti-Inflammatory Diet (IBD-AID) was initiated. We collected stool and blood samples and assessed dietary intake throughout the study. We applied advanced computational approaches to define and model complex interactions between the foods reported and the microbiome. A dense dataset comprising 553 dietary records and 340 stool samples was obtained from 22 participants. Consumption of prebiotics, probiotics, and beneficial foods correlated with increased abundance of Clostridia and Bacteroides, commonly depleted in IBD cohorts. We further show that the IBD-AID intervention affects the immune tone by lowering IL-8 and increasing GM-CSF with certain foods correlating with levels of those cytokines. By using robust predictive analytics, this study represents the first steps to detangle diet-microbiome interactions to inform personalized nutrition for patients suffering from dysbiosis-related IBD.

BackgroundP-glycoprotein (P-gp) plays a critical role in protection of the intestinal epithelia by mediating efflux of drugs/xenobiotics from the intestinal mucosa into the gut lumen. Recent studies bring to light that P-gp also confers a critical link in communication between intestinal mucosal barrier function and the innate immune system. Yet, despite knowledge for over 10 years that P-gp plays a central role in gastrointestinal homeostasis, the precise molecular mechanism that controls its functional expression and regulation remains unclear. Here, we assessed how the intestinal microbiome drives P-gp expression and function.ResultsWe have identified a “functional core” microbiome of the intestinal gut community, specifically genera within theClostridiaandBacilliclasses, that is necessary and sufficient for P-gp induction in the intestinal epithelium in mouse models. Metagenomic analysis of this core microbial community revealed that short-chain fatty acid and secondary bile acid production positively associate with P-gp expression. We have further shown these two classes of microbiota-derived metabolites synergistically upregulate P-gp expression and function in vitro and in vivo. Moreover, in patients suffering from ulcerative colitis (UC), we find diminished P-gp expression coupled to the reduction of epithelial-derived anti-inflammatory endocannabinoids and luminal content (e.g., microbes or their metabolites) with a reduced capability to induce P-gp expression.ConclusionOverall, by means of both in vitro and in vivo studies as well as human subject sample analysis, we identify a mechanistic link between cooperative functional outputs of the complex microbial community and modulation of P-gp, an epithelial component, that functions to suppress overactive inflammation to maintain intestinal homeostasis. Hence, our data support a new cross-talk paradigm in microbiome regulation of mucosal inflammation.

The reason for the striking differences in clinical outcomes of SARS-CoV-2 infected patients is still poorly understood. While most recover, a subset of people become critically ill and succumb to the disease. Thus, identification of biomarkers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment. Given that an unbalanced gut microbiome is a reflection of poor health, we aim to identify indicator species that could predict COVID-19 disease clinical outcomes. Here, for the first time and with the largest COVID-19 patient cohort reported for microbiome studies, we demonstrated that the intestinal and oral microbiome make-up predicts respectively with 92% and 84% accuracy (Area Under the Curve or AUC) severe COVID-19 respiratory symptoms that lead to death. The accuracy of the microbiome prediction of COVID-19 severity was found to be far superior to that from training similar models using information from comorbidities often adopted to triage patients in the clinic (77% AUC). Additionally, by combining symptoms, comorbidities, and the intestinal microbiota the model reached the highest AUC at 96%. Remarkably the model training on the stool microbiome found enrichment of Enterococcus faecalis, a known pathobiont, as the top predictor of COVID-19 disease severity. Enterococcus faecalis is already easily cultivable in clinical laboratories, as such we urge the medical community to include this bacterium as a robust predictor of COVID-19 severity when assessing risk stratification of patients in the clinic.

Crohn's disease (CD), a type of inflammatory bowel disease (IBD), is a chronic condition of the gastrointestinal tract that is caused by the loss of mucosal tolerance towards the commensal bacteria resulting in inflammatory responses. It has long been postulated that the gut microbiota, a complex and dynamic population of microorganisms, plays a key role in the pathogenesis of IBD. Maternal diagnosis of IBD has been identified as the greatest risk factor for IBD in offspring increasing the odds of developing the disease >4.5-fold. Moreover, babies born to mothers with IBD have demonstrated reduced gut bacterial diversity. There is accumulating evidence that the early life microbiota colonization is informed by maternal diet within the 3rd trimester of pregnancy. While babies born to mothers with IBD would pose an ideal cohort for intervention, no primary prevention measures are currently available. Therefore, we designed the MELODY (Modulating Early Life Microbiome through Dietary Intervention in Pregnancy) trial to test whether the IBD-AID™ dietary intervention during the last trimester of pregnancy can beneficially shift the microbiome of CD patients and their babies, thereby promoting a strong, effective immune system during a critical time of the immune system development. We will also test if favorable changes in the microbiome can lead to a reduced risk of postpartum CD relapse and lower mucosal inflammation in the offspring. This study will help create new opportunities to foster a healthy microbiome in the offspring at high risk of other immune-mediated diseases, potentially reducing their risk later in life. ispartof: CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS vol:18 ispartof: location:Netherlands status: published

Shigella is unique among enteric pathogens, as it invades colonic epithelia through the basolateral pole. Therefore, it has evolved the ability to breach the intestinal epithelial barrier to deploy an arsenal of effector proteins, which permits bacterial invasion and leads to a severe inflammatory response. However, the mechanisms used by Shigella to regulate epithelial barrier permeability remain unknown. To address this question, we used both an intestinal polarized model and a human ex-vivo model to further characterize the early events of host-bacteria interactions. Our results showed that secreted Serine Protease A (SepA), which belongs to the serine protease autotransporter of Enterobacteriaceae family, is responsible for critically disrupting the intestinal epithelial barrier. Such disruption facilitates bacterial transit to the basolateral pole of the epithelium, ultimately fostering the hallmarks of the disease pathology. SepA was found to cause a decrease in active LIM Kinase 1 (LIMK1) levels, a negative inhibitor of actin-remodeling proteins, namely cofilin. Correspondingly, we observed increased activation of cofilin, a major actin-polymerization factor known to control opening of tight junctions at the epithelial barrier. Furthermore, we resolved the crystal structure of SepA to elucidate its role on actin-dynamics and barrier disruption. The serine protease activity of SepA was found to be required for the regulatory effects on LIMK1 and cofilin, resulting in the disruption of the epithelial barrier during infection. Altogether, we demonstrate that SepA is indispensable for barrier disruption, ultimately facilitating Shigella transit to the basolateral pole where it effectively invades the epithelium.

BackgroundCrohn’s disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance towards the commensal microbiota. Approximately 70% of CD patients experience perianal complications. Perianal fistulizing is a predictor of poor long-term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis (CAF), a disease with clinical similarities to fistulizing CD, as a surrogate model for human fistulizing CD.ResultsBy comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show that similar to microbiome population trends in CD humans, CAF dogs microbiomes are either very dissimilar (dysbiotic) or similar, yet unique, to healthy dog’s microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance ofBacteroides vulgatusandEscherichia coliand a decreased abundance ofMegamonasspecies andPrevotella copri. These same determinant bacteria are associated with human CD.ConclusionsOur results highlight the similarities in microbiome community patterns between CAF dogs and CD humans, including overlapping determinant bacterial taxa, and support the use of CAF dogs as a surrogate model to study human fistulizing CD.

Background Caribbean Latino adults have disproportionately high prevalence of chronic disease; however, underlying mechanisms are unknown. Unique gut microbiome profiles and relation to dietary quality may underlie health disparities. Objectives To examine the dietary quality of an underrepresented group of Caribbean Latino older adults with high prevalence of chronic disease; characterize gut microbiome profiles in this cohort; determine associations between dietary quality, gut microbiome composition, and short-chain fatty acid (SCFA) production; examine associations of clinical factors (body mass index, type 2 diabetes [T2D] status, and laxative use) with gut microbiome composition. Design The study design was cross-sectional. Participants/setting Recruitment and interviews occurred at the Senior Center in Lawrence, MA, from September 2016-September 2017. A total of 20 adults aged ≥50 years, self-identified of Caribbean Latino origin, without use of antibiotics in 6 months or intestinal surgery were included in the study. Exposure and outcome measures Diet was assessed by two, 24-hour recalls and dietary quality was calculated using the Healthy Eating Index 2015 and the Mediterranean Diet Score. The gut microbiome was assessed by 16S rRNA sequencing and fecal SCFA content. Anthropometrics (ie, weight and height) were measured by a trained interviewer, and self-reported laxative use, and other self-report health outcomes (ie, T2D status) were assessed by questionnaire. Statistical analyses Faith Phylogenetic Diversity (alpha diversity) and unique fraction metric, or UniFrac (beta diversity) and nonphylogenetic metrics, including Shannon diversity index (alpha diversity) were calculated. Spearman correlations and group comparisons using Kruskal-Wallis test between alpha diversity indexes and nutrient intakes were calculated. Patterns in the microbiome were estimated using a partitioning around medoids with estimation of number of clusters, with optimum average silhouette width. Log odds were calculated to compare predefined nutrients and diet score components between microbiome clusters using multivariable logistic regression, controlling for age and sex. Pearson correlation was used to relate SCFA fecal content to individual nutrients and diet indexes. Final models were additionally adjusted for laxative use. Differences in lifestyle factors by gut microbiome cluster were tested by Fisher's exact test. Results Generally, there was poor alignment of participant's diets to either the Mediterranean Diet score or Healthy Eating Index 2015. Range in the Healthy Eating Index 2015 was 36 to 90, where only 5% (n=1) of the sample showed high adherence to the Dietary Guidelines for Americans. Mediterranean Diet scores suggested low conformance with a Mediterranean eating pattern (score range=2 to 8, where 45% scored ≤3 [poor adherence]). The gut microbiome separated into two clusters by difference in a single bacterial taxon: Prevotella copri (P copri) (permutational multivariate analysis of variance [PERMANOVA] R2=0.576, ADONIS function P=0.001). Significantly lower P copri abundance was observed in cluster 1 compared with cluster 2 (Mann-Whitney P Conclusions Two unique microbiome profiles, identified by abundance of P copri, were identified among Caribbean Latino adults. Microbiome profiles and SCFA content were associated with diet, T2D, and lifestyle. Further research is needed to determine the role of P copri and SCFA production in the risk for chronic disease and associated lifestyle predictors.

Background and Aims The inflammatory bowel disease-anti-inflammatory diet (IBD-AID) is a whole food diet designed to favor the development of an anti-inflammatory microbiome and to assist with remission in patients suffering from inflammatory bowel disease (IBD). Herein, we evaluated the effect of the IBD-AID on the gut microbiome and defined the impact of specific foods on bacteria depleted in IBD patients, as well as the clinical response to the IBD-AID. Methods A single-arm, pre-post intervention trial was performed. After a baseline period, a dietary intervention was initiated. We collected stool and blood samples throughout the study and assessed dietary intake and disease severity. We applied advanced computational approaches to define and model complex interactions between the diet, microbiota, and response to the IBD-AID. Results A dense dataset comprising 553 dietary records and 340 stool samples was compiled from 22 subjects participating in the study. The IBD-AID favored bacteria that are normally depleted in IBD cohorts and capable of producing short-chain fatty acids (SCFAs). Consumption of non-starchy vegetables, nuts, and seeds positively correlated with increased abundance of SCFA-producing bacteria, including Roseburia hominis, Eubacterium eligens,and Faecalibacterium prausnitzii. Half of the subjects completing the intervention with high diet adherence (>60%) reported a positive clinical response to the IBD-AID, with a subset of bacterial species predicting diet-induced reduction of symptoms with 67% accuracy. After the intervention, subjects also exhibited a reduction of circulating inflammatory markers. Conclusions The IBD-AID favors the growth of SCFA-producing bacteria that are depleted during IBD dysbiosis. The microbiome signatures emerging after the IBD-AID can predict response to the diet.

With aging, tryptophan metabolism is affected. Tryptophan has a crucial role in the induction of immune tolerance and the maintenance of gut microbiota. We, therefore, studied the effect of dietary tryptophan restriction in young wild‐type (WT) mice (118‐wk life span) and in DNA‐repair deficient, premature‐aged (Ercc1(−/Δ7)) mice (20‐wk life span). First, we found that the effect of aging on the distribution of B and T cells in bone marrow (BM) and in the periphery of 16‐wk‐old Ercc1(−/Δ7) mice was comparable to that in 18‐mo‐old WT mice. Dietary tryptophan restriction caused an arrest of B cell development in the BM, accompanied by diminished B cell frequencies in the periphery. In general, old Ercc1(−/Δ7) mice showed similar responses to tryptophan restriction compared with young WT mice, indicative of age‐independent effects. Dietary tryptophan restriction increased microbial diversity and made the gut microbiota composition of old Ercc1(−/Δ7) mice more similar to that of young WT mice. The decreased abundances of Alistipes and Akkermansia spp. after dietary tryptophan restriction correlated significantly with decreased B cell precursor numbers. In conclusion, we report that dietary tryptophan restriction arrests B cell development and concomitantly changes gut microbiota composition. Our study suggests a beneficial interplay between dietary tryptophan, B cell development, and gut microbial composition on several aspects of age‐induced changes.

Crohn’s disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance toward the commensal microbiota. On average, 29.5% and 42.7% CD patients experience perianal complications at 10 and 20 y after diagnosis, respectively. Perianal CD (pCD) result in high disease burden, diminished quality of life, and elevated health-care costs. Overall pCD are predictors of poor long-term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis (CAF), a disease with clinical similarities to pCD, as a surrogate model for understanding the microbial contribution of human pCD pathophysiology. By comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show CAF-dog microbiomes are either very dissimilar (dysbiotic) or similar (healthy-like), yet unique, to healthy dog’s microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance of Bacteroides vulgatus and Escherichia coli and a decreased abundance of Megamonas species and Prevotella copri. Our results mirror what have been reported in previous microbiome studies of patients with CD; particularly, CAF dogs exhibited two distinct microbiome composition: dysbiotic and healthy-like, with determinant bacterial taxa such as E. coli and P. copri that overlap what it has been found on their human counterpart. Thus, our results support the use of CAF dogs as a surrogate model to advance our understanding of microbial dynamics in pCD.

Your food is your best medicine. Nowhere else is this more real than for those suffering from inflammatory bowel disease (IBD). Thus, we developed the IBD-Anti-Inflammatory Diet (IBD-AID™) to relieve IBD symptoms while providing nutrient adequacy. The IBD-AID™ was designed to increase the diversity of bacteria that produce short-chain fatty acids (SCFAs) to modulate the local immune response. After 4 weeks on the IBD-AID™, patients have reported a reduction of symptoms and medication. Our goal is to define diet-microbiome-inflammation interactions that promote health while consuming the IBD-AID™. We posit that IBD-AID™ favors SCFA-producing bacteria resulting in dampening of inflammation and assisting patient’s remission. We recruited 19 patients with mild to severe CD or UC, to determine diet-dependent changes in the microbiota that could support the hypothesis. The study design was a single-arm, prospective, pre-post intervention trial. After a ‘baseline’ period of 4 weeks, the dietary ‘Intervention’ phase started and continued for 8–10 weeks (Fig 1). We performed metagenomic sequencing of 400+ fecal samples and analyzed 300+ food frequency questionnaires. Most (88.2%) patients achieved ≥50% diet compliance. The IBD-AID™ significantly promoted microbiota signatures that have been associated with colonic health. We found that increased intakes of prebiotics foods correlated with the abundance of SCFAs-producing members of the Bacteroides and Parabacteroides. Similarly, increase intakes of probiotics foods during intervention correlated with the abundance of Clostridium bolteae, a bacterium known to play a critical role in the induction of regulatory T cells. We found that vegetable and nuts intake -encouraged in IBD-AID™, correlated with the abundance of butyrate-producing Roseburia hominis, Eubacterium rectale, and Faecalibacterium prausnitzii. The increased abundance of those SCFAs-producing bacteria after the intervention was accompanied by declines in putative pathogenic strains, such as Escherichia sp., Alistipes sp., and Eggerthella sp. The majority (61.3%) of patients treated for at least 8 weeks, who achieved as minimum as 50% dietary compliance reported a dramatic decrease in disease severity. To examine the role of those diet-dependent microbiome signatures in inflammation, we use P-glycoprotein (P-gp) expression as a biomarker. P-gp is an ABC transporter in epithelial cells implicated in the development and persistence of chronic intestinal inflammation in IBD. We found that fecal supernatants from IBD patients adopting the IBD-AID™ induced P-gp expression. Altogether, these results uncover a novel molecular mechanism of the diet-microbiome-immune interaction allowing us to customize dietary guidelines to emphasize foods with known effect on microbiome signatures associated with health. Fig 1. Schematic representation of the study design and sampling schedule.

The American Heart Association (AHA) dietary guidelines recommend 30&ndash, 35% of energy intake (%E) be from total fat, &lt, 7%E from saturated fatty acids (SFA), and &lt, 1%E from trans fatty acid (TFA). This study evaluates the effect of AHA dietary counselling on fat intake. Between 2009 and 2014, 119 obese adults with metabolic syndrome (MetS), (71% women, average 52.5 years of age, and 34.9 kg/m2 of body mass index), received individual and group counselling on the AHA diet, over a one-year study period. Each participant attended 2 individual sessions (months 1 and 12) and 12 group sessions, at one-month intervals. At baseline and one-year, we collected three random 24-h diet recalls (two weekdays and one weekend day). Fat intake patterns over time were analyzed using paired-t test and linear mixed-effect models. There was significant variation on SFA and TFA intake per meal, being highest at dinner, in restaurants, and on weekends. Over the one-year study period, daily intake of total fat, SFA, and TFA decreased by 27%, 37% and 41%, respectively (p-value &lt, 0.01, each). Correspondingly, the percentage of participants complying with AHA&rsquo, s recommendations, increased from 25.2% to 40.2% for total fat (p-value = 0.02), from 2.5% to 20.7% for SFA (p-value &lt, 0.01), and from 45.4% to 62% for TFA (p-value = 0.02). Additionally, SFA intake for all meal types at home decreased significantly (p-value &lt, 0.05, each). AHA dietary counselling significantly increased the compliance with AHA dietary guidelines, with an eightfold increase in compliance in SFA intake. Nonetheless, ~80% of our participants still exceeded the recommended SFA intake. Substantial efforts are needed to encourage low-SFA and low-TFA food preparation at home, with strong public health policies to decrease SFA and TFA in restaurants and prepared foods.

Helicobacter pyloriis the dominant member of the gastric microbiota and has been associated with an increased risk of gastric cancer and peptic ulcers in adults.H. pyloripopulations have migrated and diverged with human populations, and health effects vary. Here, we describe the whole genome of thecag-positive strain V225d, cultured from a Venezuelan Piaroa Amerindian subject. To gain insight into the evolution and host adaptation of this bacterium, we undertook comparativeH. pylorigenomic analyses. A robust multiprotein phylogenetic tree reflects the major human migration out of Africa, across Europe, through Asia, and into the New World, placing AmerindianH. pylorias a particularly close sister group to East AsianH. pylori. In contrast, phylogenetic analysis of the host-interactive genesvacAandcagAshows substantial divergence of Amerindian from Old World forms and indicates new genotypes (e.g., VacA m3) involving these loci. Despite deletions in CagA EPIYA and CRPIA domains, V225d stimulates interleukin-8 secretion and the hummingbird phenotype in AGS cells. However, following a 33-week passage in the mouse stomach, these phenotypes were lost in isolate V225-RE, which had a 15-kb deletion in thecagpathogenicity island that truncated CagA and eliminated some of the type IV secretion system genes. Thus, the unusual V225dcagarchitecture was fully functional via conserved elements, but the natural deletion of 13cagpathogenicity island genes and the truncation of CagA impaired the ability to induce inflammation.

The mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts are covered by a layer of epithelial cells that are responsible for sensing and promoting a host immune response in order to establish the limits not only for commensal microorganisms but also for foreign organisms or particles. This is a remarkable task as the human body represents a composite of about 10 trillion human-self cells plus non-self cells from autochthonous or indigenous microbes that outnumber human cells 10:1. Hence, the homeostasis of epithelial cells that line mucosal surfaces relies on a fine-tuned immune system that patrols the boundaries between human and microbial cells. In the case of the intestine, the epithelial layer is composed of at least six epithelial cell lineages that act as a physiological barrier in addition to aiding digestion and the absorption of nutrients, water and electrolytes. In this review, we highlight the immense role of the intestinal epithelium in coordinating the mucosal innate immune response.

Gastrointestinal parasites have evolved with humans and colonize many asymptomatic subjects. We investigated the influence of microbial gastrointestinal colonization on the nutritional status of rural Amerindians (40 males and 61 females). Helicobacter pylori was detected by 13C-breath test, and intestinal parasites were detected in fecal specimens. Body morphometry and bioelectrical impedance measurements were measured. Although Amerindians showed low height and weight for age, they had an adequate body mass index, morphometric parameters, and cell mass. Intestinal parasites were detected in 99% of the subjects, with no detrimental effect on nutritional parameters. Helicobacter pylori was present in 82% of adults and half the children, and was positively correlated with improved nutritional status. Despite the high prevalence of gastrointestinal microbes often associated with disease, the studied population of Amerindians had a body morphometry and composition indicative of good nutritional status, and improved in children positive for gastric H. pylori.

Background Helicobacter pylori has diverged in parallel to its human host, leading to distinct phylogeographic populations. Recent evidence suggests that in the current human mixing in Latin America, European H. pylori (hpEurope) are increasingly dominant at the expense of Amerindian haplotypes (hspAmerind). This phenomenon might occur via DNA recombination, modulated by restriction-modification systems (RMS), in which differences in cognate recognition sites (CRS) and in active methylases will determine direction and frequency of gene flow. We hypothesized that genomes from hspAmerind strains that evolved from a small founder population have lost CRS for RMS and active methylases, promoting hpEurope’s DNA invasion. We determined the observed and expected frequencies of CRS for RMS in DNA from 7 H. pylori whole genomes and 110 multilocus sequences. We also measured the number of active methylases by resistance to in vitro digestion by 16 restriction enzymes of genomic DNA from 9 hpEurope and 9 hspAmerind strains, and determined the direction of DNA uptake in co-culture experiments of hspAmerind and hpEurope strains. Results Most of the CRS were underrepresented with consistency between whole genomes and multilocus sequences. Although neither the frequency of CRS nor the number of active methylases differ among the bacterial populations (average 8.6 ± 2.6), hspAmerind strains had a restriction profile distinct from that in hpEurope strains, with 15 recognition sites accounting for the differences. Amerindians strains also exhibited higher transformation rates than European strains, and were more susceptible to be subverted by larger DNA hpEurope-fragments than vice versa. Conclusions The geographical variation in the pattern of CRS provides evidence for ancestral differences in RMS representation and function, and the transformation findings support the hypothesis of Europeanization of the Amerindian strains in Latin America via DNA recombination.