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Background & Aims: The gut virome includes eukaryotic viruses and bacteriophages that can shape the gut bacterial community and elicit host responses. The virome can be implicated in diseases, such as irritable bowel syndrome (IBS), where gut bacteria play an important role in pathogenesis. We provide a comprehensive and longitudinal characterization of the virome, including DNA and RNA viruses and paired multi-omics data in a cohort of healthy subjects and patients with IBS., Methods: We selected 2 consecutive stool samples per subject from a longitudinal study cohort and performed metagenomic sequencing on DNA and RNA viruses after enriching for viral-like particles. Viral sequence abundance was evaluated over time, as well as in the context of diet, bacterial composition and function, metabolite levels, colonic gene expression, host genetics, and IBS subsets., Results: We found that the gut virome was temporally stable and correlated with the colonic transcriptome. We identified IBS-subset-specific changes in phage populations; Microviridae, Myoviridae, and Podoviridae species were elevated in diarrhea-predominant IBS, and other Microviridae and Myoviridae species were elevated in constipation-predominant IBS compared to healthy controls. We identified correlations between subsets of the virome and bacterial composition (unclassifiable "dark matter" and phages) and diet (eukaryotic viruses)., Conclusions: We found that the gut virome is stable over time but varies among subsets of patients with IBS. It can be affected by diet and potentially influences host function via interactions with gut bacteria and/or altering host gene expression., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Environment and diet are key factors which shape the microbiome of organisms. There is also a disparity between captive and wild animals of the same species, presumably because of the change in diet. Being able to reverse the microbiome to the wild type is thus particularly important for the reintroduction efforts of Critically Endangered animals. The Javan slow loris (Nycticebus javanicus) is a suitable model, being kept in the thousands within rescue centres throughout Southeast Asia. With next-generation sequencing, we show how a naturalistic diet impacts the gut microbiome of captive slow lorises (Primates: Nycticebus). A comparison of the microbiome of wild animals with captive animals that had been fed a standard captive or improved diet reveals strong microbiome differences between wild and captive animals; however, diet changes failed to alter the microbiome of captive populations significantly. Bifidobacterium was the most abundant genus in wild animals (46.7%) while Bacteroides (11.6%) and Prevotella (18.9%) were the most abundant in captive animals fed the captive and improved diets, respectively. Correlation analyses of nutrients with microbial taxa suggest important implications in using nutrition to suppress potential pathogens, with soluble fibre and water-soluble carbohydrates both being associated with opposing microbiome profiles. The improved diet significantly increased microbe diversity, which exemplifies the importance of high fibre diets; however, wild individuals had lower diversity, which contradicts recent studies. Detection of methanogens appeared to be dependent on diet and whether the animals were living in captivity or in the wild. This study highlights the potential of nutrition in modulating the microbiome of animals prior to release. Unexpectedly, the results were not as significant as has been suggested in recent studies.

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined. Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation. Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8. Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation. Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394., (© 2017 American Society for Nutrition.)

Background: The effect of whole grains on the regulation of energy balance remains controversial. Objective: We aimed to determine the effects of substituting whole grains for refined grains, independent of body weight changes, on energy-metabolism metrics and glycemic control. Design: The study was a randomized, controlled, parallel-arm controlled-feeding trial that was conducted in 81 men and postmenopausal women [49 men and 32 women; age range: 40-65 y; body mass index (in kg/m 2 ): <35.0]. After a 2-wk run-in period, participants were randomly assigned to consume 1 of 2 weight-maintenance diets for 6 wk. Diets differed in whole-grain and fiber contents [mean ± SDs: whole grain-rich diet: 207 ± 39 g whole grains plus 40 ± 5 g dietary fiber/d; refined grain-based diet: 0 g whole grains plus 21 ± 3 g dietary fiber/d] but were otherwise similar. Energy metabolism and body-composition metrics, appetite, markers of glycemic control, and gut microbiota were measured at 2 and 8 wk. Results: By design, body weight was maintained in both groups. Plasma alkylresorcinols, which are biomarkers of whole-grain intake, increased in the whole grain-rich diet group (WG) but not in the refined grain-based diet group (RG) ( P -diet-by-time interaction < 0.0001). Beta ± SE changes (ΔWG compared with ΔRG) in the resting metabolic rate (RMR) (43 ± 25 kcal/d; P = 0.04), stool weight (76 ± 12 g/d; P < 0.0001), and stool energy content (57 ± 17 kcal/d; P = 0.003), but not in stool energy density, were higher in the WG. When combined, the favorable energetic effects in the WG translated into a 92-kcal/d (95% CI: 28, 156-kcal/d) higher net daily energy loss compared with that of the RG ( P = 0.005). Prospective consumption ( P = 0.07) and glycemia after an oral-glucose-tolerance test ( P = 0.10) trended toward being lower in the WG than in the RG. When nonadherent participants were excluded, between-group differences in stool energy content and glucose tolerance increased, and between-group differences in the RMR and prospective consumption were not statistically significant. Conclusion: These findings suggest positive effects of whole grains on the RMR and stool energy excretion that favorably influence energy balance and may help explain epidemiologic associations between whole-grain consumption and reduced body weight and adiposity. This trial was registered at clinicaltrials.gov as NCT01902394., (© 2017 American Society for Nutrition.)

Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity. Objective: We assessed the effects of diets rich in WGs compared with refined grains (RGs) on immune and inflammatory responses, gut microbiota, and microbial products in healthy adults while maintaining subject body weights. Design: After a 2-wk provided-food run-in period of consuming a Western-style diet, 49 men and 32 postmenopausal women [age range: 40-65 y, body mass index (in kg/m 2 ) <35] were assigned to consume 1 of 2 provided-food weight-maintenance diets for 6 wk. Results: Compared with the RG group, the WG group had increased plasma total alkyresorcinols (a measure of WG intake) ( P < 0.0001), stool weight ( P < 0.0001), stool frequency ( P = 0.02), and short-chain fatty acid (SCFA) producer Lachnospira [false-discovery rate (FDR)-corrected P = 0.25] but decreased pro-inflammatory Enterobacteriaceae (FDR-corrected P = 0.25). Changes in stool acetate ( P = 0.02) and total SCFAs ( P = 0.05) were higher in the WG group than in the RG group. A positive association was shown between Lachnospira and acetate (FDR-corrected P = 0.002) or butyrate (FDR-corrected P = 0.005). We also showed that there was a higher percentage of terminal effector memory T cells ( P = 0.03) and LPS-stimulated ex vivo production of tumor necrosis factor-α ( P = 0.04) in the WG group than in the RG group, which were positively associated with plasma alkylresorcinol concentrations. Conclusion: The short-term consumption of WGs in a weight-maintenance diet increases stool weight and frequency and has modest positive effects on gut microbiota, SCFAs, effector memory T cells, and the acute innate immune response and no effect on other markers of cell-mediated immunity or systemic and gut inflammation. This trial was registered at clinicaltrials.gov as NCT01902394., (© 2017 American Society for Nutrition.)

Objective: To characterise the influence of diet on abdominal symptoms, anal gas evacuation, intestinal gas distribution and colonic microbiota in patients complaining of flatulence., Design: Patients complaining of flatulence (n=30) and healthy subjects (n=20) were instructed to follow their usual diet for 3 days (basal phase) and to consume a high-flatulogenic diet for another 3 days (challenge phase)., Results: During basal phase, patients recorded more abdominal symptoms than healthy subjects in daily questionnaires (5.8±0.3 vs 0.4±0.2 mean discomfort/pain score, respectively; p=<0.0001) and more gas evacuations by an event marker (21.9±2.8 vs 7.4±1.0 daytime evacuations, respectively; p=0.0001), without differences in the volume of gas evacuated after a standard meal (262±22 and 265±25 mL, respectively). On flatulogenic diet, both groups recorded more abdominal symptoms (7.9±0.3 and 2.8±0.4 discomfort/pain, respectively), number of gas evacuations (44.4±5.3 and 21.7±2.9 daytime evacuations, respectively) and had more gas production (656±52 and 673±78 mL, respectively; p<0.05 vs basal diet for all). When challenged with flatulogenic diet, patients' microbiota developed instability in composition, exhibiting variations in the main phyla and reduction of microbial diversity, whereas healthy subjects' microbiota were stable. Taxa from Bacteroides fragilis or Bilophila wadsworthia correlated with number of gas evacuations or volume of gas evacuated, respectively., Conclusions: Patients complaining of flatulence have a poor tolerance of intestinal gas, which is associated with instability of the microbial ecosystem.

Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.

Coevolution of mammals and their gut microbiota has profoundly affected their radiation into myriad habitats. We used shotgun sequencing of microbial community DNA and targeted sequencing of bacterial 16S ribosomal RNA genes to gain an understanding of how microbial communities adapt to extremes of diet. We sampled fecal DNA from 33 mammalian species and 18 humans who kept detailed diet records, and we found that the adaptation of the microbiota to diet is similar across different mammalian lineages. Functional repertoires of microbiome genes, such as those encoding carbohydrate-active enzymes and proteases, can be predicted from bacterial species assemblages. These results illustrate the value of characterizing vertebrate gut microbiomes to understand host evolutionary histories at a supraorganismal level.