Viral dysbiosis in children with new-onset celiac disease

Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray–Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray–Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.

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Effect of Bovine MFGM and LF in Infant Formula on Gut Microbiome and Metabolome at Four Months of Age

Current Developments in Nutrition ◽

10.1093/cdn/nzab027 ◽

2021 ◽

Author(s):

Maciej Chichlowski ◽

Nicholas Bokulich ◽

Cheryl L Harris ◽

Jennifer L Wampler ◽

Fei Li ◽

...

Keyword(s):

Infant Formula ◽

Beta Diversity ◽

Milk Fat ◽

Alpha Diversity ◽

Illumina Miseq ◽

Rrna Gene ◽

Term Infants ◽

Linear Discriminant ◽

Alpha And Beta Diversity ◽

Metabolite Profiles

Abstract Background Milk fat globule membrane (MFGM) and lactoferrin (LF) are human milk bioactive components demonstrated to support gastrointestinal (GI) and immune development. Significantly fewer diarrhea and respiratory-associated adverse events through 18 months of age were previously reported in healthy term infants fed a cow's milk-based infant formula with added source of bovine MFGM and bovine LF through 12 months of age. Objectives To compare microbiota and metabolite profiles in a subset of study participants. Methods Stool samples were collected at Baseline (10–14 days of age) and Day 120 (MFGM + LF: 26, Control: 33). Bacterial community profiling was performed via16S rRNA gene sequencing (Illumina MiSeq) and alpha and beta diversity were analyzed (QIIME 2). Differentially abundant taxa were determined using Linear discriminant analysis effect size (LefSE) and visualized (Metacoder). Untargeted stool metabolites were analyzed (HPLC/mass spectroscopy) and expressed as the fold-change between group means (Control: MFGM + LF ratio). Results Alpha diversity increased significantly in both groups from baseline to 4 months. Subtle group differences in beta diversity were demonstrated at 4 months (Jaccard distance; R2 = 0.01, P = 0.042). Specifically, Bacteroides uniformis and Bacteroides plebeius were more abundant in the MFGM + LF group at 4 months. Metabolite profile differences for MFGM + LF vs Control included: lower fecal medium chain fatty acids, deoxycarnitine, and glycochenodeoxycholate, and some higher fecal carbohydrates and steroids (P < 0.05). After applying multiple test correction, the differences in stool metabolomics were not significant. Conclusions Addition of bovine MFGM and LF in infant formula was associated with subtle differences in stool microbiome and metabolome by four months of age, including increased prevalence of Bacteroides species. Stool metabolite profiles may be consistent with altered microbial metabolism. Trial registration: https://clinicaltrials.gov/ct2/show/NCT02274883).

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Gut Microbiome in Psoriasis: An Updated Review

Pathogens ◽

10.3390/pathogens9060463 ◽

2020 ◽

Vol 9 (6) ◽

pp. 463

Author(s):

Mariusz Sikora ◽

Albert Stec ◽

Magdalena Chrabaszcz ◽

Aleksandra Knot ◽

Anna Waskiel-Burnat ◽

...

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Large Scale ◽

Skin Diseases ◽

Intestinal Barrier ◽

Alpha Diversity ◽

Current Data ◽

Intestinal Microbiome ◽

Microbial Composition ◽

Alpha And Beta Diversity

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.

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Impact of Early Life Antibiotic Exposure and Neonatal Hyperoxia on the Murine Microbiome and Lung Injury

Scientific Reports ◽

10.1038/s41598-019-51506-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Melissa H. Althouse ◽

Christopher Stewart ◽

Weiwu Jiang ◽

Bhagavatula Moorthy ◽

Krithika Lingappan

Keyword(s):

Lung Injury ◽

Beta Diversity ◽

Alpha Diversity ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Antibiotic Exposure ◽

Neonatal Mice ◽

Intestinal Dysbiosis ◽

Neonatal Hyperoxia

Abstract Cross talk between the intestinal microbiome and the lung and its role in lung health remains unknown. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have an impact on the preterm lung. We hypothesized that perinatal antibiotic exposure leads to long-term intestinal dysbiosis and increased alveolar simplification in a murine hyperoxia model. Pregnant C57BL/6 wild type dams and neonatal mice were treated with antibiotics before and/or immediately after delivery. Control mice received phosphate-buffered saline (PBS). Neonatal mice were exposed to 95% oxygen for 4 days or room air. Microbiome analysis was performed using 16S rRNA gene sequencing. Pulmonary alveolarization and vascularization were analyzed at postnatal day (PND) 21. Perinatal antibiotic exposure modified intestinal beta diversity but not alpha diversity in neonatal mice. Neonatal hyperoxia exposure altered intestinal beta diversity and relative abundance of commensal bacteria in antibiotic treated mice. Hyperoxia disrupted pulmonary alveolarization and vascularization at PND 21; however, there were no differences in the degree of lung injury in antibiotic treated mice compared to vehicle treated controls. Our study suggests that exposure to both hyperoxia and antibiotics early in life may cause long-term alterations in the intestinal microbiome, but intestinal dysbiosis may not significantly influence neonatal hyperoxic lung injury.

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Effects of Helicobacter pylori Infection on the Oral Microbiota of Reflux Esophagitis Patients

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.732613 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tian Liang ◽

Fang Liu ◽

Lijun Liu ◽

Zhiying Zhang ◽

Wenxue Dong ◽

...

Keyword(s):

Helicobacter Pylori ◽

Reflux Esophagitis ◽

Beta Diversity ◽

High Throughput Sequencing ◽

Alpha Diversity ◽

Vital Role ◽

Size Analysis ◽

Oral Microbiota ◽

Linear Discriminant ◽

Microbial Network

The human oral microbiota plays a vital role in maintaining metabolic homeostasis. To explore the relationship between Helicobacter pylori (Hp) and reflux esophagitis, we collected 86 saliva samples from reflux esophagitis patients (RE group) and 106 saliva samples from healthy people (C group) for a high-throughput sequencing comparison. No difference in alpha diversity was detected between the RE and the C groups, but beta diversity of the RE group was higher than the C group. Bacteroidetes was more abundant in the RE group, whereas Firmicutes was more abundant in the C group. The linear discriminant analysis effect size analysis demonstrated that the biomarkers of the RE group were Prevotella, Veillonella, Leptotrichia, and Actinomyces, and the biomarkers of the C group were Lautropia, Gemella, Rothia, and Streptococcus. The oral microbial network structure of the C group was more complex than that of the RE group. Second, to explore the effect of Hp on the oral microbiota of RE patients, we performed the 14C-urea breath test on 45 of the 86 RE patients. We compared the oral microbiota of 33 Hp-infected reflux esophagitis patients (REHpp group) and 12 non-Hp-infected reflux esophagitis patients (REHpn group). No difference in alpha diversity was observed between the REHpn and REHpp groups, and beta diversity of the REHpp group was significantly lower than that of the REHpn group. The biomarkers in the REHpp group were Veillonella, Haemophilus, Selenomonas, Megasphaera, Oribacterium, Butyrivibrio, and Campylobacter; and the biomarker in the REHpn group was Stomatobaculum. Megasphaera was positively correlated with Veillonella in the microbial network of the REHpp group. The main finding of this study is that RE disturbs the human oral microbiota, such as increased beta diversity. Hp infection may inhibit this disorderly trend.

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Nasal and gut microbiota for sows of different health status within six commercial swine farms from one swine production system

10.1101/596130 ◽

2019 ◽

Author(s):

Andréia Gonçalves Arruda ◽

Loic Deblais ◽

Vanessa Hale ◽

Monique Pairis-Garcia ◽

Vishal Srivastava ◽

...

Keyword(s):

Health Status ◽

Gut Microbiota ◽

Beta Diversity ◽

Animal Health ◽

Alpha Diversity ◽

Considerable Proportion ◽

Upper Respiratory Tract ◽

Fecal Samples ◽

Cull Sows ◽

Nasal Microbiota

AbstractSow culling is an essential practice in swine herds to optimize animal health and productivity; and cull sows represent a considerable proportion of the herd at any given time point. Even though recent studies have reported that the microbiome is associated with susceptibility to diseases, the microbiome in the cull sow population has not been explored. The main objective of this study was to investigate whether there were differences in abundance and diversity of microbes encountered in the gut and upper respiratory tract of sows of different health status (healthy, cull, and compromised cull sows) and different farms. Farms were visited once, 30 individual fecal and nasal swab samples were obtained per farm; and pooled across animals by health status and farm in pools of five. Genomic DNA was extracted and samples were subjected to MiSeq 16S rRNA sequencing using Illumina MiSeq. Diversity analyses were conducted using QIIME. Alpha diversity was analyzed using observed OTUs, PD Whole Tree, and Chao1; and beta diversity was assessed using weighted UniFrac. The mean number of OTUs was 3,846.97±9,078.87 and 28,747.92±14,090.50 for nasal and fecal pooled samples, respectively. Diversity of the nasal microbiota was low compared to the gut microbiota. For nasal samples, there was a difference in diversity between samples from farms 1-6 using the Chao1 metric (p = 0.0005); and weighted beta diversity values indicated clustering by health status. For fecal samples, there was no difference in diversity between compromised, cull, and healthy sows; or between samples from farms 1-6. Weighted PCoA analyses showed an influence of farm of origin on the diversity of pooled fecal samples. Finally, differences at the genus level were found in the fecal microbiota composition of sows of different health status and farm of origin; but not for nasal microbiota.

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APOE Genetics Influence Murine Gut Microbiome

10.21203/rs.3.rs-746611/v1 ◽

2021 ◽

Author(s):

Diana J. Zajac ◽

Stefan J. Green ◽

Lance A. Johnson ◽

Steven Estus

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Univariate Analysis ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Linear Discriminant ◽

Fecal Microbiome ◽

Female Mice ◽

The Impact

Abstract Background: Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we tested whether these results are confirmed by using mice that were maintained under ideal conditions for microbiome analyses. Methods: To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, APOE3 mice were crossed to APOE2 or APOE4 mice prior to the study, and the resulting heterozygous progeny crossed further to generate the study mice. To maximize environmental homogeneity, mice with mixed genotypes were housed together and used bedding from the cages was mixed and added back as a portion of new bedding. Fecal samples were obtained from mice at three-, five- and seven-months of age, and microbiota analyzed by 16S ribosomal RNA gene amplicon sequencing. APOE2/E2 and APOE2/E3 mice were categorized as APOE2, APOE3/E4 and APOE4/E4 mice were categorized as APOE4, and APOE3/E3 mice were categorized as APOE3. Linear discriminant analysis of Effect Size (LefSe) identified taxa associated with APOE status, depicted as cladograms to show phylogenetic relatedness. The influence of APOE status was tested onalpha-diversity (Shannon H index) and beta-diversity (principal coordinate analyses and PERMANOVA). Individual taxa associated with APOE status were identified by classical univariate analysis. Whether findings in the APOE mice were replicated in humans was evaluated by using published microbiome genome wide association data. Results: Cladograms revealed robust differences with APOE in male mice and limited differences in female mice. The richness and evenness (alpha-diversity) and microbial community composition (beta-diversity) of the fecal microbiome was robustly associated with APOE status in male but not female mice. Classical univariate analysis revealed individual taxa that were significantly increased or decreased with APOE, illustrating a stepwise APOE2-APOE3-APOE4 pattern of association. The Clostridia class, Clostridiales order, Ruminococacceae family and related genera increased with APOE2 status. The Erysipelotrichia phylogenetic branch increased with APOE4 status, a finding that extended to humans.Conclusions: In this study wherein mice were maintained in an ideal fashion for microbiome studies, gut microbiome profiles were strongly and significantly associated with APOE status in male APOE-TR mice. Erysipelotrichia in particular appears to increase with APOE4 in both mice and humans. Further evaluation of these findings in humans, as well as studies evaluating the impact of the APOE-associated microbiota on disease-relevant phenotypes, will be necessary to determine if alterations in the gut microbiome represents a novel mechanism whereby APOE alleles impact disease.

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Abstract P277: Lower Gut Microbial Diversity in Non-alcoholic Fatty Liver Disease: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Circulation ◽

10.1161/circ.141.suppl_1.p277 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Jessica S Williams-Nguyen ◽

Mark H Kuniholm ◽

Zheng Wang ◽

Jin Choul Chai ◽

Jee-Young Moon ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiome ◽

Beta Diversity ◽

Fatty Liver Disease ◽

Alpha Diversity ◽

Abundant Species ◽

Shannon Index ◽

Health Study ◽

Hispanic Community ◽

Latino Adults

Introduction: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and a leading cause of chronic liver disease in the United States (US). Prevalence of both conditions is higher in US Hispanics/Latinos compared to non-Hispanic whites. Composition of the gut microbiome, comprising the microorganisms in the gastrointestinal tract, has been associated with both NAFLD and obesity in animal and human studies, but there is currently no consensus on which microbial changes are associated with these two conditions. Data on the relation of the gut microbiome with NAFLD in Hispanic/Latino populations are limited. Hypothesis: We hypothesized that gut bacterial diversity is associated with NAFLD in Hispanic/Latino adults. Methods: This analysis included 2587 Hispanic/Latino adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) with fecal samples. The gut microbiome was characterized using shotgun metagenomic sequencing and taxonomic classification by the SHOGUN pipeline with the RefSeq 82 prokaryotic genome database. NAFLD was defined based on gender-specific liver function test thresholds developed in the National Health and Nutrition Examination Survey (NHANES) after excluding participants with other known causes of liver dysfunction. Alpha and beta diversity were compared between groups defined by NAFLD and obesity using multinomial logistic regression and PERMANOVA, respectively. The difference in relative abundance for the 15 most abundant species were compared using the Wilcoxon rank sum test. Results: There were 395 (15%) NAFLD cases among 2587 participants, and 1718 (66%) were women. Prevalence of obesity (BMI ≥ 30) was 58% and 42% among those with and without NAFLD, respectively. Higher bacterial alpha diversity (Shannon index) was associated with lower odds of NAFLD with (OR = 0.58, p = 0.0005) or without obesity (OR = 0.70, p = 0.04) compared to participants with neither condition after adjusting for age, gender, Hispanic background, diabetes, dyslipidemia and hypertension. In the same model, higher Shannon index was also associated with lower odds of obesity in the absence of NALFD (OR = 0.78, p = 0.01). Beta diversity (Bray-Curtis) did not differ significantly by NAFLD/obesity groups (p = 0.78) or by NAFLD alone (p = 0.30). Among the 15 most abundant species across samples, 4 ( Bacteroides uniformis , Odoribacter splanchnicus , Oscillibacter sp. ER4, and Alistipes shahii ) had significantly lower abundance in those with NAFLD compared to those without NAFLD irrespective of obesity. Conclusion: This study reveals that bacterial alpha diversity but not beta diversity is independently associated with the related conditions, NAFLD and obesity, in US Hispanic/Latino adults. Future work will explore associations between NAFLD and functional capacity of gut microbial components as well as considering relevant host genetic variants in this population.

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Pancreatic cancer intratumoral microbiome and characteristics within paired patient samples.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.744 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 744-744

Author(s):

Sonal Suresh Noticewala ◽

Daniel Lin ◽

Ramez Kouzy ◽

Anirban Maitra ◽

Lauren Elizabeth Colbert ◽

...

Keyword(s):

Pancreatic Cancer ◽

Beta Diversity ◽

Pancreatic Tumor ◽

Bacterial Species ◽

Alpha Diversity ◽

Intestinal Microbiome ◽

Sequencing Analysis ◽

Normal Pancreas ◽

16S Sequencing ◽

Resected Tumor

744 Background: While most studies evaluating the microbiome in gastrointestinal cancers analyze stool, little is known about the microbiota of the peri-tumoral and intra-tumoral environment. Here, we evaluated the intra-tumoral and peri-tumoral (duodenum and normal pancreas) microbiome for paired duodenal, normal pancreas and resected tumor specimens from pancreatic cancer patients. The purpose of this study was to describe the similarities and differences within patient microbiota. Methods: Fifteen specimens from 5 patients with pancreatic cancer were collected during surgical resection. Genomic bacterial DNA was extracted from these specimens and underwent 16S rRNA sequencing. Alpha (Inverse Simpson) and beta diversity were calculated, and relative abundances of individual bacterial species were compared. Sorensen distance was used the evaluate the spread in beta diversity between paired sample types. Results: Of the five patients who underwent resection, the following baseline characteristics were obtained: median age = 65 years (range 55 -80 years), 2/5 patients were treated with gemcitabine/abraxane, 3/5 patients were treated with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX); 4/5 patients received pre-operative radiation. 16s sequencing analysis of the pancreatic tumor showed the dominant genus to be Escherichia/Shigella (10.6%). Bradyrhizobium (10.1 %) was dominant in the normal pancreas . Escherichia/Shigella (14.3%) was abundant in the duodenum. There was a trend towards higher alpha diversity in tumor vs. normal duodenum/ pancreas (p = 0.12). Sorensen distance was statistically different between sample types (p = 0.004), with duodenal samples most consistent (distance = 67.82), and tumor vs. normal pancreas (81.86) and tumor vs. other tumor samples the most heterogeneous (78.5). Conclusions: This pilot data suggests that the pancreatic tumor microbiome is distinct from the normal pancreas and duodenal microbiome, which indicates tumor specific bacteria should be studied. In future studies, intra-tumoral microbiome may be more relevant to associations with outcomes and treatment response than stool or intestinal microbiome studies.

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Both Gut Microbiota and Differentially Expressed Proteins Are Relevant to the Development of Obesity

BioMed Research International ◽

10.1155/2020/5376108 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Yuchuan Li ◽

Qiuxia Liu ◽

Chunting Peng ◽

Bing Ruan

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Peripheral Blood ◽

Bacterial Communities ◽

Alpha Diversity ◽

Differentially Expressed ◽

Standard Diet ◽

Differentially Expressed Proteins ◽

Fecal Samples ◽

Linear Discriminant

Although the role of the gut microbiota in obesity has recently received considerable attention, the exact mechanism is unclear. This study was aimed at investigating the profiles of bacterial communities in fecal samples and differentially expressed proteins (DEPs) in the peripheral blood in mice fed a high-fat diet (HFD) and standard diet (SD) and at providing new insights into the pathogenesis of obesity. The profiles of bacterial communities in fecal samples and DEPs in the peripheral blood were characterized in mice fed HFD and SD, respectively. The levels of 3 DEPs increased in HFD mice. The alpha diversity was significantly lower after 4 and 12 weeks in HFD mice. The beta diversity was higher after 4, 8, and 12 weeks in HFD mice. A total of 16 gut bacterial clades were significantly different with the linear discriminant analysis (LDA) score higher than 4 over time. The relative abundance levels of Proteobacteria and Deferribacteres were higher, while those of Bacteroidetes and Firmicutes were lower in HFD mice at the phylum level. The relative abundance of Desulfovibrionaceae and Rikenellaceae increased in HFD mice at the family level. The relative abundance of the Bacteroidetes_S24-7_group and Lachnospiraceae was lower in HFD mice. The gut microbiota had a significant correlation with serum lipid indexes and expression of DEPs at the phylum and family levels. The changes in the gut microbiota of HFD mice and their associations with the levels of inflammatory proteins could be one of the major etiological mechanisms underlying obesity.

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Diet Modification and Not Timed Feeding Strategies Result in Intestinal Microbiome Alterations (P21-030-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz041.p21-030-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Marie van der Merwe ◽

Sunita Sharma ◽

Jade Caldwell ◽

Nicholas Smith ◽

Richard Bloomer ◽

...

Keyword(s):

High Fat Diet ◽

Beta Diversity ◽

Diversity Index ◽

Alpha Diversity ◽

Taxonomic Composition ◽

Intestinal Microbiome ◽

Feeding Strategies ◽

High Fat ◽

Microbiome Composition ◽

Intestinal Length

Abstract Objectives Time-restricted feeding strategies have been shown to normalize obesity parameters, even under high fat feeding conditions. The objective of this study is to examine whether timed feeding alters parameters of gut health or intestinal microbiome composition. Methods C57BL/6 male mice were randomized to Chow or a high fat diet (HFD) for 6 weeks, followed by a switch from HFD to 1) Chow (sChow), 2) Purified Vegan – Daniel Fast (DF), 3) HFD ad lib, 4) HFD time restricted (TRF), 5) HFD alternative day fasting (ADF), or 6) HFD 60% caloric restriction (CR) for an additional 8 weeks. Results We observed that body mass gain was reduced for all intervention groups (P ≤ 0.0001). Small intestinal length and cecal weight were increased in Chow, sChow and DF (P ≤ 0.02), while total cecal short chain fatty acid (SCFA) concentration was non-significantly increased for all groups consuming the HFD. Proprionate was specifically increased in the Chow, sChow and DF groups (P ≤ 0.02). Chow fed microbiota remained stable in taxonomic composition and alpha diversity (Shannon diversity index) throughout the study. HF fed microbiota displayed lower alpha diversity along with reduced phylum levels of Bacteroidetes and increase Firmicutes. Animals switched from HF to Chow demonstrated a rapid transition in taxonomic composition, alpha, and beta diversity that initially resembled HF, but clustered closely with Chow by weeks 4 and 8 of intervention. After 8 weeks on the respective dietary protocols, alpha diversity of the DF was most similar to Chow fed animals and also resulted in the largest increase in Bacteriodetes and largest decrease in Firmicutes. Beta diversity (weighted UniFrac) showed Chow, sChow, and DF clustered together, while high fat fed groups (HF, CR, ADF, and TRF) clustered. Compared with HF controls, CR and TRF led to a relative increase in the classes Clostridia, Deferribacteres and Deltaproteobacteria. The taxonomic composition and alpha diversity of ADF fasting resembled HF under fed conditions, while ADF under fasting conditions more closely resembled CR and TRF. Conclusions In conclusion, timed feeding on a high fat diet did not result in significant changes in the microbiome, demonstrating that diet, and not fasting is the major determinant for microbiome composition. Funding Sources University of Memphis & Children's Foundation Research Institute, Memphis.

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