Publications by authors named "Joseph F Petrosino"

166 Publications

Habitual Sleep Duration and the Colonic Mucosa-Associated Gut Microbiota in Humans-A Pilot Study.

Clocks Sleep 2021 Jul 1;3(3):387-397. Epub 2021 Jul 1.

Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

We examined the association between the colonic adherent microbiota and nocturnal sleep duration in humans. In a cross-sectional study, 63 polyp-free adults underwent a colonoscopy and donated 206 mucosal biopsies. The gut microbiota was profiled using the 16S rRNA gene sequencing targeting the V4 region. The sequence reads were processed using UPARSE and DADA2, respectively. Lifestyle factors, including sleep habits, were obtained using an interviewer-administered questionnaire. We categorized the participants into short sleepers (<6 h per night; = 16) and normal sleepers (6-8 h per night; = 47) based on self-reported data. Differences in bacterial biodiversity and the taxonomic relative abundance were compared between short vs. normal sleepers, followed by multivariable analysis. A false discovery rate-adjusted value ( value) < 0.05 indicated statistical significance. The bacterial community composition differed in short and normal sleepers. The relative abundance of was significantly lower (0.38% vs. 1.25%) and that of was significantly higher (0.14% vs. 0.08%) in short sleepers than in normal sleepers ( values < 0.01). The difference was confirmed in the multivariable analysis. Nocturnal sleep duration was associated with the bacterial community composition and structure in the colonic gut microbiota in adults.
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http://dx.doi.org/10.3390/clockssleep3030025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293063PMC
July 2021

Spatial Characteristics of Colonic Mucosa-Associated Gut Microbiota in Humans.

Microb Ecol 2021 Jul 5. Epub 2021 Jul 5.

Texas Medical Center Digestive Disease Center, Houston, TX, 77030, USA.

Limited data exist on the spatial distribution of the colonic bacteria in humans. We collected the colonic biopsies from five segments of 27 polyp-free adults and collected feces from 13 of them. We sequenced the V4 region of the bacterial 16S rRNA gene using the MiSeq platform. The sequencing data were assigned to the amplicon sequence variant (ASV) using SILVA. Biodiversity and the relative abundance of the ASV were compared across the colonic segments and between the rectal and fecal samples. Bacterial functional capacity was assessed using Tax4fun. Each individual had a unique bacterial community composition (Weighted Bray-Curtis P value = 0.001). There were no significant differences in richness, evenness, community composition, and the taxonomic structure across the colon segments in all the samples. Firmicutes (47%), Bacteroidetes (39%), and Proteobacteria (6%) were the major phyla in all segments, followed by Verrucomicrobia, Fusobacteria, Desulfobacterota, and Actinobacteria. There were 15 genera with relative abundance > 1%, including Bacteroides, Faecalibacterium, Escherichia/Shigella, Sutterella, Akkermansia, Parabacteroides, Prevotella, Lachnoclostridium, Alistipes, Fusobacterium, Erysipelatoclostridium, and four Lachnospiraceae family members. Intra-individually, the community compositional dissimilarity was the greatest between the cecum and the rectum. There were significant differences in biodiversity and the taxonomic structure between the rectal and fecal bacteria. The bacterial community composition and structure were homogeneous across the large intestine in adults. The inter-individual variability of the bacteria was greater than inter-segment variability. The rectal and fecal bacteria differed in the community composition and structure.
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http://dx.doi.org/10.1007/s00248-021-01789-6DOI Listing
July 2021

A study of innate immune kinetics reveals a role for a chloride transporter in a virulent Francisella tularensis type B strain.

Microbiologyopen 2021 02;10(2):e1170

The Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX, USA.

Tularemia is a zoonotic disease of global proportions. Francisella tularensis subspecies tularensis (type A) and holarctica (type B) cause disease in healthy humans, with type A infections resulting in higher mortality. Repeated passage of a type B strain in the mid-20th century generated the Live Vaccine Strain (LVS). LVS remains unlicensed, does not protect against high inhalational doses of type A, and its exact mechanisms of attenuation are poorly understood. Recent data suggest that live attenuated vaccines derived from type B may cross-protect against type A. However, there is a dearth of knowledge regarding virulent type B pathogenesis and its capacity to stimulate the host's innate immune response. We therefore sought to increase our understanding of virulent type B in vitro characteristics using strain OR96-0246 as a model. Adding to our knowledge of innate immune kinetics in macrophages following infection with virulent type B, we observed robust replication of strain OR96-0246 in murine and human macrophages, reduced expression of pro-inflammatory cytokine genes from "wild type" type B-infected macrophages compared to LVS, and delayed macrophage cell death suggesting that virulent type B may suppress macrophage activation. One disruption in LVS is in the gene encoding the chloride transporter ClcA. We investigated the role of ClcA in macrophage infection and observed a replication delay in a clcA mutant. Here, we propose its role in acid tolerance. A greater understanding of LVS attenuation may reveal new mechanisms of pathogenesis and inform strategies toward the development of an improved vaccine against tularemia.
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http://dx.doi.org/10.1002/mbo3.1170DOI Listing
February 2021

Gut Microbiome Profiles and Associated Metabolic Pathways in HIV-Infected Treatment-Naïve Patients.

Cells 2021 Feb 13;10(2). Epub 2021 Feb 13.

Laboratório de Imunologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, Florianópolis, SC 88034-040, Brazil.

The normal composition of the intestinal microbiota is a key factor for maintaining healthy homeostasis, and accordingly, dysbiosis is well known to be present in HIV-1 patients. This article investigates the gut microbiota profile of antiretroviral therapy-naive HIV-1 patients and healthy donors living in Latin America in a cohort of 13 HIV positive patients (six elite controllers, EC, and seven non-controllers, NC) and nine healthy donors (HD). Microbiota compositions in stool samples were determined by sequencing the V3-V4 region of the bacterial 16S rRNA, and functional prediction was inferred using PICRUSt. Several taxa were enriched in EC compared to NC or HD groups, including , , , , and . In addition, our data indicate that the route of infection is an important factor associated with changes in gut microbiome composition, and we extend these results by identifying several metabolic pathways associated with each route of infection. Importantly, we observed several bacterial taxa that might be associated with different viral subtypes, such as , which were more abundant in patients infected by HIV subtype B, and enrichment in patients infected by subtype C. In conclusion, our data brings a significant contribution to the understanding of dysbiosis-associated changes in HIV infection and describes, for the first time, differences in microbiota composition according to HIV subtypes. These results warrant further confirmation in a larger cohort of patients.
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http://dx.doi.org/10.3390/cells10020385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917727PMC
February 2021

Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation.

Commun Biol 2021 02 22;4(1):237. Epub 2021 Feb 22.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Diversity of the gut microbiome is associated with higher response rates for cancer patients receiving immunotherapy but has not been investigated in patients receiving radiation therapy. Additionally, current studies investigating the gut microbiome and outcomes in cancer patients may not have adjusted for established risk factors. Here, we sought to determine if diversity and composition of the gut microbiome was independently associated with survival in cervical cancer patients receiving chemoradiation. Our study demonstrates that the diversity of gut microbiota is associated with a favorable response to chemoradiation. Additionally, compositional variation among patients correlated with short term and long-term survival. Short term survivor fecal samples were significantly enriched in Porphyromonas, Porphyromonadaceae, and Dialister, whereas long term survivor samples were significantly enriched in Escherichia Shigella, Enterobacteriaceae, and Enterobacteriales. Moreover, analysis of immune cells from cervical tumor brush samples by flow cytometry revealed that patients with a high microbiome diversity had increased tumor infiltration of CD4+ lymphocytes as well as activated subsets of CD4 cells expressing ki67+ and CD69+ over the course of radiation therapy. Modulation of the gut microbiota before chemoradiation might provide an alternative way to enhance treatment efficacy and improve treatment outcomes in cervical cancer patients.
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http://dx.doi.org/10.1038/s42003-021-01741-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900251PMC
February 2021

Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial.

Diabetologia 2021 May 30;64(5):1079-1092. Epub 2021 Jan 30.

Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.

Aims/hypothesis: Oral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome.

Methods: A phase I/II randomised controlled trial was performed in a single clinical study centre in Germany. Participants were 44 islet autoantibody-negative children aged 6 months to 2.99 years who had a first-degree relative with type 1 diabetes and a susceptible HLA DR4-DQ8-containing genotype. Children were randomised 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months using a web-based computer system. The primary outcome was immune efficacy pre-specified as induction of antibody or T cell responses to insulin and measured in a central treatment-blinded laboratory.

Results: Randomisation was performed in 44 children. One child in the placebo group was withdrawn after the first study visit and data from 22 insulin-treated and 21 placebo-treated children were analysed. Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in children who received both insulin (54.5%) and placebo (66.7%), and the trial did not demonstrate an effect on its primary outcome (p = 0.54). In exploratory analyses, there was preliminary evidence that the immune response and gut microbiome were modified by the INS genotype Among children with the type 1 diabetes-susceptible INS genotype (n = 22), antibody responses to insulin were more frequent in insulin-treated (72.7%) as compared with placebo-treated children (18.2%; p = 0.03). T cell responses to insulin were modified by treatment-independent inflammatory episodes.

Conclusions/interpretation: The study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptible INS genotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells.

Trial Registration: Clinicaltrials.gov NCT02547519 FUNDING: The main funding source was the German Center for Diabetes Research (DZD e.V.).
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http://dx.doi.org/10.1007/s00125-020-05376-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012335PMC
May 2021

The gut microbiome contributes to blood-brain barrier disruption in spontaneously hypertensive stroke prone rats.

FASEB J 2021 02;35(2):e21201

Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA.

In recent years, it has become apparent that the gut microbiome can influence the functioning and pathological states of organs and systems throughout the body. In this study, we tested the hypothesis that the gut microbiome has a major role in the disruption of the blood-brain barrier (BBB) in the spontaneously hypertensive stroke prone rats (SHRSP), an animal model for hypertensive cerebral small vessel disease (CSVD). Loss of BBB is thought to be an early and initiating component to the full expression of CSVD in animal models and humans. To test this hypothesis, newly born SHRSP pups were placed with foster dams of the SHRSP strain or dams of the WKY strain, the control strain that does not demonstrate BBB dysfunction or develop hypertensive CSVD. Similarly, WKY pups were placed with foster dams of the same or opposite strain. The rationale for cross fostering is that the gut microbiomes are shaped by environmental bacteria of the foster dam and the nesting surroundings. Analysis of the bacterial genera in feces, using 16S rRNA analysis, demonstrated that the gut microbiome in the rat pups was influenced by the foster dam. SHRSP offspring fostered on WKY dams had systolic blood pressures (SBPs) that were significantly decreased by 26 mmHg (P < .001) from 16-20 weeks, compared to SHRSP offspring fostered on SHRSP dams. Similarly WKY offspring fostered on SHRSP dams had significantly increased SBP compared to WKY offspring fostered on WKY dams, although the magnitude of SBP change was not as robust. At ~20 weeks of age, rats fostered on SHRSP dams showed enhanced inflammation in distal ileum regardless of the strain of the offspring. Disruption of BBB integrity, an early marker of CSVD onset, was improved in SHRSPs that were fostered on WKY dams when compared to the SHRSP rats fostered on SHRSP dams. Although SHRSP is a genetic model for CSVD, environmental factors such as the gut microbiota of the foster dam have a major influence in the loss of BBB integrity.
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http://dx.doi.org/10.1096/fj.202001117RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238036PMC
February 2021

Houston hurricane Harvey health (Houston-3H) study: assessment of allergic symptoms and stress after hurricane Harvey flooding.

Environ Health 2021 Jan 19;20(1). Epub 2021 Jan 19.

Department of Epidemiology and Population Health, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.

Background: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall.

Methods: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 unique participants from four sites across Harris County at two times: within approximately 1-month of Harvey (T1, n = 206) and approximately 12-months after Harvey (T2, n = 266), including 125 individuals who participated at both time points. Using a self-administered questionnaire, participants reported details on demographics, flood-related exposures, and health outcomes, including allergic symptoms and stress.

Results: The majority of participants reported hurricane-related flooding in their homes at T1 (79.1%) and T2 (87.2%) and experienced at least one allergic symptom after the hurricane (79.4% at T1 and 68.4% at T2). In general, flood-exposed individuals were at increased risk of upper respiratory tract allergic symptoms, reported at both the T1 and T2 time points, with exposures to dirty water and mold associated with increased risk of multiple allergic symptoms. The mean stress score of study participants at T1 was 8.0 ± 2.1 and at T2, 5.1 ± 3.2, on a 0-10 scale. Participants who experienced specific flood-related exposures reported higher stress scores when compared with their counterparts, especially 1 year after Harvey. Also, a supplementary paired-samples analysis showed that reports of wheezing, shortness of breath, and skin rash did not change between T1 and T2, though other conditions were less commonly reported at T2.

Conclusion: These initial Houston-3H findings demonstrate that flooding experiences that occurred as a consequence of Hurricane Harvey had lasting impacts on the health of Houstonians up to 1 year after the hurricane.
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http://dx.doi.org/10.1186/s12940-021-00694-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816385PMC
January 2021

Microbiome for Mars: surveying microbiome connections to healthcare with implications for long-duration human spaceflight, virtual workshop, July 13, 2020.

Microbiome 2021 01 4;9(1). Epub 2021 Jan 4.

Department of Medicine, The University of Texas at Houston Health Sciences Center, 6431 Fannin St, Houston, TX, 77030, USA.

The inaugural "Microbiome for Mars" virtual workshop took place on July 13, 2020. This event assembled leaders in microbiome research and development to discuss their work and how it may relate to long-duration human space travel. The conference focused on surveying current microbiome research, future endeavors, and how this growing field could broadly impact human health and space exploration. This report summarizes each speaker's presentation in the order presented at the workshop.
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http://dx.doi.org/10.1186/s40168-020-00951-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781430PMC
January 2021

Oligonucleotide Capture Sequencing of the SARS-CoV-2 Genome and Subgenomic Fragments from COVID-19 Individuals.

bioRxiv 2020 Dec 11. Epub 2020 Dec 11.

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10. Heterogeneous allelic frequencies along the 20kb ORF1ab gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.
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http://dx.doi.org/10.1101/2020.12.11.421057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743067PMC
December 2020

Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis.

Gut 2020 Dec 16. Epub 2020 Dec 16.

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

Objective: Necrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother's own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC.

Design: We performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644).

Results: Concentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of and higher relative abundance of in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by spp and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or having NEC.

Conclusion: These results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification and novel avenues for supplements that may prevent life-threatening disease.
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http://dx.doi.org/10.1136/gutjnl-2020-322771DOI Listing
December 2020

Fructan-sensitive children with irritable bowel syndrome have distinct gut microbiome signatures.

Aliment Pharmacol Ther 2021 02 13;53(4):499-509. Epub 2020 Dec 13.

Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

Background: Dietary fructans may worsen gastrointestinal symptoms in children with irritable bowel syndrome (IBS).

Aim: To determine whether gut microbiome composition and function are associated with childhood IBS fructan-induced symptoms.

Methods: Faecal samples were collected from 38 children aged 7-17 years with paediatric Rome III IBS, who previously completied a double-blind, randomised, placebo-controlled crossover (fructan vs maltodextrin) trial. Fructan sensitivity was defined as an increase of ≥30% in abdominal pain frequency during the fructan diet. Gut microbial composition was determined via 16Sv4 rDNA sequencing. LEfSe evaluated taxonomic composition differences. Tax4Fun2 predicted microbial fructan metabolic pathways.

Results: At baseline, 17 fructan-sensitive (vs 21 fructan-tolerant) subjects had lower alpha diversity (q < 0.05) and were enriched in the genus Holdermania. In contrast, fructan-tolerant subjects were enriched in 14 genera from the class Clostridia. During the fructan diet, fructan-sensitive (vs tolerant) subjects were enriched in both Agathobacter (P = 0.02) and Cyanobacteria (P = 0.0001). In contrast, fructan-tolerant subjects were enriched in three genera from the Clostridia class. Comparing the fructan vs maltodextrin diet, fructan-sensitive subjects had a significantly increased relative abundance of Bifidobacterium (P = 0.02) while fructan-tolerant subjects had increased Anaerostipes (P = 0.03) during the fructan diet. Only fructan-sensitive subjects had a trend towards increased predicted β-fructofuranosidase during the fructan vs maltodextrin diet.

Conclusions: Fructan-sensitive children with IBS have distinct gut microbiome signatures. These microbiome signatures differ both at baseline and in response to a fructan challenge.
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http://dx.doi.org/10.1111/apt.16204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281336PMC
February 2021

Baseline Oral Microbiome and All-cancer Incidence in a Cohort of Nonsmoking Mexican American Women.

Cancer Prev Res (Phila) 2021 Mar 4;14(3):383-392. Epub 2020 Dec 4.

Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Given the increasing evidence that the oral microbiome is involved in obesity, diabetes, and cancer risk, we investigated baseline oral microbiota profiles in relation to all-cancer incidence among nonsmoking women enrolled in a Texas cohort of first- and second-generation immigrants of Mexican origin. We characterized the 16Sv4 rDNA microbiome in oral mouthwash samples collected at baseline from a representative subset of 305 nonsmoking women, ages 20-75 years. We evaluated within- (alpha) and between-sample (beta) diversity by incident cancer status and applied linear discriminant analysis (LDA) effect size analysis to assess differentially abundant taxa. Diversity and candidate taxa in relation to all-cancer incidence were evaluated in multivariable-adjusted Cox regression models. Over 8.8 median years of follow-up, 31 incident cancer cases were identified and verified. Advanced age, greater acculturation, and cardiometabolic risk factors were associated with all-cancer incidence. Higher alpha diversity (age-adjusted < 0.01) and distinct biological communities ( = 0.002) were observed by incident cancer status. Each unit increase in the Shannon diversity index yielded >8-fold increase in all-cancer and obesity-related cancer risk [multivariable-adjusted HR (95% confidence interval), 8.11 (3.14-20.94) and 10.72 (3.30-34.84), respectively] with similar findings for the inverse Simpson index. was enriched among women who did not develop cancer, while , and were higher among women who developed cancer (LDA score ≥ 3; q-value < 0.01). This initial study of oral microbiota and overall cancer risk in nonsmoking Mexican American women suggests the readily accessible oral microbiota as a promising biomarker. PREVENTION RELEVANCE: Mexican American women suffer a disproportionate burden of chronic health conditions that increase cancer risk. Few investigations of the microbiome, a key determinant of host health, have been conducted among this group. Oral microbiota profiles may provide early and accessible cancer biomarker data on invasive bacteria or community disruptions.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137515PMC
March 2021

Metagenomic Information Recovery from Human Stool Samples Is Influenced by Sequencing Depth and Profiling Method.

Genes (Basel) 2020 11 21;11(11). Epub 2020 Nov 21.

Diversigen Inc., Houston, TX 77021, USA.

Sequencing of the 16S rRNA gene (16S) has long been a go-to method for microbiome characterization due to its accessibility and lower cost compared to shotgun metagenomic sequencing (SMS). However, 16S sequencing rarely provides species-level resolution and cannot provide direct assessment of other taxa (e.g., viruses and fungi) or functional gene content. Shallow shotgun metagenomic sequencing (SSMS) has emerged as an approach to bridge the gap between 16S sequencing and deep metagenomic sequencing. SSMS is cost-competitive with 16S sequencing, while also providing species-level resolution and functional gene content insights. In the present study, we evaluated the effects of sequencing depth on marker gene-mapping- and alignment-based annotation of bacteria in healthy human stool samples. The number of identified taxa decreased with lower sequencing depths, particularly with the marker gene-mapping-based approach. Other annotations, including viruses and pathways, also showed a depth-dependent effect on feature recovery. These results refine the understanding of the suitability and shortcomings of SSMS, as well as annotation tools for metagenomic analyses in human stool samples. Results may also translate to other sample types and may open the opportunity to explore the effect of sequencing depth and annotation method.
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http://dx.doi.org/10.3390/genes11111380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700633PMC
November 2020

Alcohol use alters the colonic mucosa-associated gut microbiota in humans.

Nutr Res 2020 11 17;83:119-128. Epub 2020 Sep 17.

Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, TX, USA; Texas Medical Center Digestive Disease Center, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA. Electronic address:

Alcohol misuse is a risk factor for many adverse health outcomes. Alcohol misuse has been associated with an imbalance of gut microbiota in preclinical models and alcoholic diseases. We hypothesized that daily alcohol use would change the community composition and structure of the human colonic gut microbiota. Thirty-four polyp-free individuals donated 97 snap-frozen colonic biopsies. Microbial DNA was sequenced for the 16S ribosomal RNA gene hypervariable region 4. The SILVA database was used for operational taxonomic unit classification. Alcohol use was assessed using a food frequency questionnaire. We compared the biodiversity and relative abundance of the taxa among never drinkers (ND, n = 9), former drinkers (FD, n = 10), current light drinkers (LD, <2 drinks daily, n = 9), and current heavy drinkers (HD, ≥2 drinks daily, n = 6). False discovery rate-adjusted P values (q values) < .05 indicated statistical significance. HD had the lowest α diversity (Shannon index q value < 0.001), and HD's microbial composition differed the most from the other groups (P value = .002). LD had the highest relative abundance of Akkermansia (q values < 0.001). HD had the lowest relative abundance of Subdoligranulum, Roseburia, and Lachnospiraceaeunc91005 but the highest relative abundance of Lachnospiraceaeunc8895 (all q values < 0.05). The multivariable negative binomial regression model supported these observations. ND and FD had a similar microbial profile. Heavy alcohol use was associated with impaired gut microbiota that may partially mediate its effect on health outcomes.
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http://dx.doi.org/10.1016/j.nutres.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669629PMC
November 2020

Oral Health and the Altered Colonic Mucosa-Associated Gut Microbiota.

Dig Dis Sci 2020 Sep 24. Epub 2020 Sep 24.

Department of Medicine, Baylor College of Medicine, 2002 Holcombe Blvd, MS152, Houston, 77030, TX, USA.

Background: Systemic diseases have been associated with oral health and gut microbiota. We examined the association between oral health and the community composition and structure of the adherent colonic gut microbiota.

Methods: We obtained 197 snap-frozen colonic biopsies from 62 colonoscopy-confirmed polyp-free individuals. Microbial DNA was sequenced for the 16S rRNA V4 region using the Illumina MiSeq, and the sequences were assigned to the operational taxonomic unit based on SILVA. We used a questionnaire to ascertain tooth loss, gum disease, and lifestyle factors. We compared biodiversity and relative abundance of bacterial taxa based on the amount of tooth loss and the presence of gum disease. The multivariable negative binomial regression model for panel data was used to estimate the association between the bacterial count and oral health. False discovery rate-adjusted P value (q value) < .05 indicated statistical significance.

Results: More tooth loss and gum disease were associated with lower bacterial alpha diversity. The relative abundance of Faecalibacterium was lower (q values < .05) with more tooth loss. The association was significant after adjusting for age, ethnicity, obesity, smoking, alcohol use, hypertension, diabetes, and the colon segment. The relative abundance of Bacteroides was higher in those with gum disease.

Conclusions: Oral health was associated with alteration in the community composition and structure of the adherent gut bacteria in the colon. The reduced anti-inflammatory Faecalibacterium in participants with more tooth loss may indicate systemic inflammation. Future studies are warranted to confirm our findings and investigate the systemic role of Faecalibacterium.
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http://dx.doi.org/10.1007/s10620-020-06612-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987909PMC
September 2020

Longitudinal Changes in Early Nasal Microbiota and the Risk of Childhood Asthma.

Pediatrics 2020 10 15;146(4). Epub 2020 Sep 15.

Department of Paediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Objectives: Although the airway microbiota is a highly dynamic ecology, the role of longitudinal changes in airway microbiota during early childhood in asthma development is unclear. We aimed to investigate the association of longitudinal changes in early nasal microbiota with the risk of developing asthma.

Methods: In this prospective, population-based birth cohort study, we followed children from birth to age 7 years. The nasal microbiota was tested by using 16S ribosomal RNA gene sequencing at ages 2, 13, and 24 months. We applied an unsupervised machine learning approach to identify longitudinal nasal microbiota profiles during age 2 to 13 months (the primary exposure) and during age 2 to 24 months (the secondary exposure) and examined the association of these profiles with the risk of physician-diagnosed asthma at age 7 years.

Results: Of the analytic cohort of 704 children, 57 (8%) later developed asthma. We identified 4 distinct longitudinal nasal microbiota profiles during age 2 to 13 months. In the multivariable analysis, compared with the persistent dominance profile during age 2 to 13 months, the persistent sparsity profile was associated with a significantly higher risk of asthma (adjusted odds ratio, 2.74; 95% confidence interval, 1.20-6.27). Similar associations were observed between the longitudinal changes in nasal microbiota during age 2 to 24 months and risk of asthma.

Conclusions: Children with an altered longitudinal pattern in the nasal microbiota during early childhood had a high risk of developing asthma. Our data guide the development of primary prevention strategies (eg, early identification of children at high risk and modification of microbiota) for childhood asthma. These observations present a new avenue for risk modification for asthma (eg, microbiota modification).
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http://dx.doi.org/10.1542/peds.2020-0421DOI Listing
October 2020

Effect of Antibiotics on Gut and Vaginal Microbiomes Associated with Cervical Cancer Development in Mice.

Cancer Prev Res (Phila) 2020 12 11;13(12):997-1006. Epub 2020 Sep 11.

Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.

Antibiotics affect microbial diversity in the gut, leading to dysbiosis and impaired immunity. However, the impact of antibiotics on microbial communities at other sites, such as vagina is less understood. It is also not clear whether changes induced by antibiotics in both microbiomes affect the development of cervical cancer. In this study, we utilized the murine model to evaluate these questions. We show that oral application of broad-spectrum antibiotics in mice changed not only diversity, but composition and sharing of gut and vaginal microbiomes in mice and influenced cervical cancer development in an orthotopic tumor model. Antibiotics decreased richness and diversity indexes in the gut but increased them in the vagina. Some beneficial taxa, such as , and increased their abundance in the vagina while other pathogenic species, such as , were decreased. As a result of the changes, mice with greater richness and diversity of the vaginal microbiome after antibiotics exposure were less likely developed tumors. No association between richness and diversity of the gut microbiome and tumor development was identified.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0103DOI Listing
December 2020

Impact of Diabetes on the Gut and Salivary IgA Microbiomes.

Infect Immun 2020 11 16;88(12). Epub 2020 Nov 16.

Center for Infectious Disease, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, Texas, USA.

Mucosal surfaces like those present in the lung, gut, and mouth interface with distinct external environments. These mucosal gateways are not only portals of entry for potential pathogens but also homes to microbial communities that impact host health. Secretory immunoglobulin A (SIgA) is the single most abundant acquired immune component secreted onto mucosal surfaces and, via the process of immune exclusion, shapes the architecture of these microbiomes. Not all microorganisms at mucosal surfaces are targeted by SIgA; therefore, a better understanding of the SIgA-coated fraction may identify the microbial constituents that stimulate host immune responses in the context of health and disease. Chronic diseases like type 2 diabetes are associated with altered microbial communities (dysbiosis) that in turn affect immune-mediated homeostasis. 16S rRNA gene sequencing of SIgA-coated/uncoated bacteria (IgA-Biome) was conducted on stool and saliva samples of normoglycemic participants and individuals with prediabetes or diabetes ( = 8/group). These analyses demonstrated shifts in relative abundance in the IgA-Biome profiles between normoglycemic, prediabetic, or diabetic samples distinct from that of the overall microbiome. Differences in IgA-Biome alpha diversity were apparent for both stool and saliva, while overarching bacterial community differences (beta diversity) were also observed in saliva. These data suggest that IgA-Biome analyses can be used to identify novel microbial signatures associated with diabetes and support the need for further studies exploring these communities. Ultimately, an understanding of the IgA-Biome may promote the development of novel strategies to restructure the microbiome as a means of preventing or treating diseases associated with dysbiosis at mucosal surfaces.
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http://dx.doi.org/10.1128/IAI.00301-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671898PMC
November 2020

Oligonucleotide capture sequencing of the SARS-CoV-2 genome and subgenomic fragments from COVID-19 individuals.

bioRxiv 2020 Jul 27. Epub 2020 Jul 27.

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA, 77030.

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10. Heterogeneous allelic frequencies along the 20kb ORF1ab gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.
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http://dx.doi.org/10.1101/2020.07.27.223495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402036PMC
July 2020

Rationale, design and baseline characteristics of the Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Diabetes Obes Metab 2020 11 20;22(11):1976-1984. Epub 2020 Aug 20.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Aim: To investigate the role of the gut microbiome in regulating key insulin homeostasis traits (insulin sensitivity, insulin secretion and insulin clearance) whose dysfunction leads to type 2 diabetes (T2D).

Materials And Methods: The Microbiome and Insulin Longitudinal Evaluation Study (MILES) focuses on African American and non-Hispanic white participants aged 40-80 years without diabetes. Three study visits are planned (at baseline, 15 and 30 months). Baseline measurements include assessment of the stool microbiome and administration of an oral glucose tolerance test, which will yield indexes of insulin sensitivity, insulin secretion and insulin clearance. The gut microbiome profile (composition and function) will be determined using whole metagenome shotgun sequencing along with analyses of plasma short chain fatty acids. Additional data collected include dietary history, sociodemographic factors, health habits, anthropometry, medical history, medications and family history. Most assessments are repeated 15 and 30 months following baseline.

Results: After screening 875 individuals, 129 African American and 224 non-Hispanic white participants were enrolled. At baseline, African American participants have higher blood pressure, weight, body mass index, waist and hip circumferences but similar waist-hip ratio compared with the non-Hispanic white participants. On average, African American participants are less insulin-sensitive and have higher acute insulin secretion and lower insulin clearance.

Conclusions: The longitudinal design and robust characterization of potential mediators will allow for the assessment of glucose and insulin homeostasis and gut microbiota as they change over time, improving our ability to discern causal relationships between the microbiome and the insulin homeostasis traits whose deterioration determines T2D, setting the stage for future microbiome-directed therapies to prevent and treat T2D.
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http://dx.doi.org/10.1111/dom.14145DOI Listing
November 2020

Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019.

bioRxiv 2020 Feb 13. Epub 2020 Feb 13.

A novel coronavirus (nCoV-2019) was the cause of an outbreak of respiratory illness detected in Wuhan, Hubei Province, China in December of 2019. Genomic analyses of nCoV-2019 determined a 96% resemblance with a coronavirus isolated from a bat in 2013 (RaTG13); however, the receptor binding motif (RBM) of these two genomes share low sequence similarity. This divergence suggests a possible alternative source for the RBM coding sequence in nCoV-2019. We identified high sequence similarity in the RBM between nCoV-2019 and a coronavirus genome reconstructed from a viral metagenomic dataset from pangolins possibly indicating a more complex origin for nCoV-2019.
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http://dx.doi.org/10.1101/2020.02.07.939207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217297PMC
February 2020

SMRT Sequencing of Paramecium Bursaria Chlorella Virus-1 Reveals Diverse Methylation Stability in Adenines Targeted by Restriction Modification Systems.

Front Microbiol 2020 19;11:887. Epub 2020 May 19.

Department of Microbiology, The University of Tennessee, Knoxville, Knoxville, TN, United States.

Chloroviruses (family ) infect eukaryotic, freshwater, unicellular green algae. A unique feature of these viruses is an abundance of DNA methyltransferases, with isolates dedicating up to 4.5% of their protein coding potential to these genes. This diversity highlights just one of the long-standing values of the chlorovirus model system; where group-wide epigenomic characterization might begin to elucidate the function(s) of DNA methylation in large dsDNA viruses. We characterized DNA modifications in the prototype chlorovirus, PBCV-1, using single-molecule real time (SMRT) sequencing ( PacBio). Results were compared to total available sites predicted based on DNA sequence alone. SMRT-software detected N6-methyl-adenine (m6A) at GATC and CATG recognition sites, motifs previously shown to be targeted by PBCV-1 DNA methyltransferases M.CviAI and M. AII, respectively. At the same time, PacBio analyses indicated that 10.9% of the PBCV-1 genome had large interpulse duration ratio (ipdRatio) values, the primary metric for DNA modification identification. These events represent 20.6x more sites than can be accounted for by all available adenines in GATC and CATG motifs, suggesting base or backbone modifications other than methylation might be present. To define methylation stability, we cross-compared methylation status of each GATC and CATG sequence in three biological replicates and found ∼81% of sites were stably methylated, while ∼2% consistently lack methylation. The remaining 17% of sites were stochastically methylated. When methylation status was analyzed for both strands of each target, we show that palindromes existed in completely non-methylated states, fully-methylated states, or hemi-methylated states, though GATC sites more often lack methylation than CATG sequences. Given that both sequences are targeted by not just methyltransferases, but by restriction endonucleases that are together encoded by PBCV-1 as virus-originating restriction modification (RM) systems, there is strong selective pressure to modify all target sites. The finding that most instances of non-methylation are associated with hemi-methylation is congruent with observations that hemi-methylated palindromes are resistant to cleavage by restriction endonucleases. However, sites where hemi-methylation is conserved might represent a unique regulatory function for PBCV-1. This study serves as a baseline for future investigation into the epigenomics of chloroviruses and their giant virus relatives.
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http://dx.doi.org/10.3389/fmicb.2020.00887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248222PMC
May 2020

Dietary inflammatory potential in relation to the gut microbiome: results from a cross-sectional study.

Br J Nutr 2020 11 1;124(9):931-942. Epub 2020 Jun 1.

Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX77030, USA.

Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and β-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.
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http://dx.doi.org/10.1017/S0007114520001853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554089PMC
November 2020

The Fecal Microbiome in Infants With Biliary Atresia Associates With Bile Flow After Kasai Portoenterostomy.

J Pediatr Gastroenterol Nutr 2020 06;70(6):789-795

Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine/Texas Children's Hospital.

Background: Biliary atresia's (BA) response to surgical Kasai portoenterostomy (KP) is uneven and dependent upon bile flow; 50% of infants require a liver transplant by 24 months. We hypothesized that the microbiome may identify and associate with outcomes in BA.

Methods: Stool samples were collected from infants with cholestasis (n = 15), 8 of which with BA were followed longitudinally.16S sequencing was performed on all samples (n = 45). Whole Genome Sequencing (WGS) was performed on BA pre-KP samples (n = 8). Infants with BA, other forms of cholestasis, BA infants with very good bile flow (VGBF) and not (nVGBF) (VGBF dichotomized by TSBA <40 μmol/L by 6 months) were compared.

Results: Of the 8 infants with BA, 4 infants had VGBF. Microbial richness was inversely proportional to degree of cholestasis (P = 0.046). Increased Bifidobacterium abundance associated with VGBF (P = 0.03) and decreased cholestasis (P < 0.01) at 1 month post-KP. Pre-KP, community structure differed in infants with BA versus other cholestasis. Interestingly, infants who subsequently achieved VGBF had increased diversity (P = 0.03) and different community structure at the pre-KP time point. WGS corroborated Bifidobacterium's pre-KP importance.

Conclusions: The microbiome differs between infants with BA and other cholestasis. It additionally differs between infants with BA who have good and poor bile flow, and thus outcomes, post-KP. These differences are seen even before KP. These data suggest that bile influences the development of the infant microbiome and that there may be possible influences of the pre- and post-KP microbiome on bile flow after KP. Further larger studies are needed to confirm these findings.
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http://dx.doi.org/10.1097/MPG.0000000000002686DOI Listing
June 2020

Rotavirus infection induces glycan availability to promote ileum-specific changes in the microbiome aiding rotavirus virulence.

Gut Microbes 2020 09 13;11(5):1324-1347. Epub 2020 May 13.

Alkek Center for Metagenomic and Microbiome Research, Baylor College of Medicine , Houston, TX, USA.

Multiple studies have identified changes within the gut microbiome in response to diarrheal-inducing bacterial pathogens. However, examination of the microbiome in response to viral pathogens remains understudied. Compounding this, many studies use fecal samples to assess microbiome composition; which may not accurately mirror changes within the small intestine, the primary site for most enteric virus infections. As a result, the functional significance of small intestinal microbiome shifts during infection is not well defined. To address these gaps, rotavirus-infected neonatal mice were examined for changes in bacterial community dynamics, host gene expression, and tissue recovery during infection. Profiling bacterial communities using 16S rRNA sequencing suggested significant and distinct changes in ileal communities in response to rotavirus infection, with no significant changes for other gastrointestinal (GI) compartments. At 1-d post-infection, we observed a loss in species from the ileum, but an increase in and , both of which exhibit mucin-digesting capabilities. Concomitant with the bacterial community shifts, we observed a loss of mucin-filled goblet cells in the small intestine at d 1, with recovery occurring by d 3. Rotavirus infection of mucin-producing cell lines and human intestinal enteroids (HIEs) stimulated release of stored mucin granules, similar to findings. , incubation of mucins with or members resulted in significant glycan degradation, which altered the binding capacity of rotavirus and . Taken together, these data suggest that the response to and recovery from rotavirus-diarrhea is unique between sub-compartments of the GI tract and may be influenced by mucin-degrading microbes.
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http://dx.doi.org/10.1080/19490976.2020.1754714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524290PMC
September 2020

Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects.

J Proteomics 2020 04 9;217:103645. Epub 2020 Jan 9.

Advanced Technology Core, Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, United States of America; Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America.

Murine studies showed that disruption of circadian clock rhythmicity could lead to cancer and metabolic syndrome. Time-restricted feeding can reset the disrupted clock rhythm, protect against cancer and metabolic syndrome. Based on these observations, we hypothesized that intermittent fasting for several consecutive days without calorie restriction in humans would induce an anticarcinogenic proteome and the key regulatory proteins of glucose and lipid metabolism. Fourteen healthy subjects fasted from dawn to sunset for over 14 h daily. Fasting duration was 30 consecutive days. Serum samples were collected before 30-day intermittent fasting, at the end of 4th week during 30-day intermittent fasting, and one week after 30-day intermittent fasting. An untargeted serum proteomic profiling was performed using ultra high-performance liquid chromatography/tandem mass spectrometry. Our results showed that 30-day intermittent fasting was associated with an anticancer serum proteomic signature, upregulated key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. These findings suggest that fasting from dawn to sunset for 30 consecutive days can be preventive and adjunct therapy in cancer, metabolic syndrome, and several cognitive and neuropsychiatric diseases. SIGNIFICANCE: Our study has important clinical implications. Our results showed that intermittent fasting from dawn to sunset for over 14 h daily for 30 consecutive days was associated with an anticancer serum proteomic signature and upregulated key regulatory proteins of glucose and lipid metabolism, insulin signaling, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, obesity, diabetes, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. Importantly, these findings occurred in the absence of any calorie restriction and significant weight loss. These findings suggest that intermittent fasting from dawn to sunset can be a preventive and adjunct therapy in cancer, metabolic syndrome and Alzheimer's disease and several neuropsychiatric diseases.
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http://dx.doi.org/10.1016/j.jprot.2020.103645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429999PMC
April 2020

Maternal Fish Consumption in Pregnancy Is Associated with a -Dominant Microbiome Profile in Infants.

Curr Dev Nutr 2020 Jan 19;4(1):nzz133. Epub 2019 Dec 19.

Division of General Pediatrics, Department of Pediatrics, MassGeneral Hospital for Children, Boston, MA, USA.

National guidelines suggest that pregnant women consume 2-3 servings of fish weekly and often focus exclusively on limiting mercury exposure. We examined if meeting this recommendation in the third trimester of pregnancy was associated with differences in infant fecal microbiota composition and diversity. We used multinomial regression to analyze data from 114 infant-mother dyads. Applying 16S rRNA gene sequencing, we identified 3 infant fecal microbiota profiles: dominant, dominant, and dominant. We found that 20% of mothers met the recommended fish consumption, and those infants whose mothers met the recommendation were more likely to have a -dominant profile than an -dominant profile (RR ratio: 4.61; 95% CI: 1.40, 15.15; = 0.01). In multivariable models, the significant association persisted (< 0.05). Our findings support the need to expand recommendations focusing on the beneficial effects of fish consumption on the infant fecal microbiota profile.
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http://dx.doi.org/10.1093/cdn/nzz133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923185PMC
January 2020

The BE GONE trial study protocol: a randomized crossover dietary intervention of dry beans targeting the gut microbiome of overweight and obese patients with a history of colorectal polyps or cancer.

BMC Cancer 2019 Dec 18;19(1):1233. Epub 2019 Dec 18.

Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1340, Houston, TX, TX 77030, USA.

Background: Mouse and human studies support the promise of dry beans to improve metabolic health and to lower cancer risk. In overweight/obese patients with a history of colorectal polyps or cancer, the Beans to Enrich the Gut microbiome vs. Obesity's Negative Effects (BE GONE) trial will test whether and how an increase in the consumption of pre-cooked, canned dry beans within the context of usual diet and lifestyle can enhance the gut landscape to improve metabolic health and reduce cancer risk.

Methods/design: This randomized crossover trial is designed to characterize changes in (1) host markers spanning lipid metabolism, inflammation, and obesity-related cancer risk; (2) compositional and functional profiles of the fecal microbiome; and (3) host and microbial metabolites. With each subject serving as their own control, the trial will compare the participant's usual diet with (intervention) and without (control) dry beans. Canned, pre-cooked dry beans are provided to participants and the usual diet continually assessed and monitored. Following a 4-week run-in and equilibration period, each participant provides a total of 5 fasting blood and 6 stool samples over a total period of 16 weeks. The intervention consists of a 2-week ramp-up of dry bean intake to 1 cup/d, which is then continued for an additional 6 weeks. Intra- and inter-individual outcomes are assessed across each crossover period with consideration of the joint or modifying effects of the usual diet and baseline microbiome.

Discussion: The BE GONE trial is evaluating a scalable dietary prevention strategy targeting the gut microbiome of high-risk patients to mitigate the metabolic and inflammatory effects of adiposity that influence colorectal cancer risk, recurrence, and survival. The overarching scientific goal is to further elucidate interactions between diet, the gut microbiome, and host metabolism. Improved understanding of the diet-microbiota interplay and effective means to target these relationships will be key to the future of clinical and public health approaches to cancer and other major diet- and obesity-related diseases.

Trial Registration: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02843425. First posted July 25, 2016; last verified January 25, 2019.
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http://dx.doi.org/10.1186/s12885-019-6400-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921460PMC
December 2019
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