Advancing human gut microbiota research by considering gut transit time

Procházková, Nicola; Falony, Gwen; Dragsted, Lars Ove; Licht, Tine Rask; Raes, Jeroen; Roager, Henrik Munch

doi:10.1136/gutjnl-2022-328166

Cited by 109 publications

(127 citation statements)

References 226 publications

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“…Studies from the 1970s already showed that ECs can have profound impact on gut motility [17,28,29]. Current evidence suggests that gut transit time affects the gut microbial composition and function [30]. Here we found that concentration of ECs varied between proximal (V1) and distal colon (V4).…”

Section: Discussionsupporting

confidence: 53%

Dynamics of lipidome in a colon simulator

Kråkström

Alves

Dickens

et al. 2022

Preprint

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Current evidence suggests that gut microbiome derived lipids play crucial role in the regulation of host lipid metabolism. However, not much is known about the dynamics of gut microbial lipids within the distinct gut biogeographic. Here we employed targeted and untargeted lipidomics in the in vitro derived feces. Simulated intestinal chyme was collected from in vitro gut vessels (V1to V4), representing proximal to distal parts of the colon after 24 and 48 h with/without PDX treatment. In total 44 simulated chyme samples were collected from the in vitro colon simulator. Factor analysis showed that vessel and time had the strongest impact on the simulated intestinal chyme lipid profiles. We found that levels of phosphatidylcholines, sphingomyelins, triacylglycerols and endocannabinoids were altered in at least one vessel (V1 to V4) during simulation. We also found that concentrations of triacylglycerols, diacylglycerols and endocannabinoids changed with time (24 vs. 48 h simulation). Together, we found that the simulated intestinal chyme revealed a wide range of lipids that remained altered in different compartments of the human colon model over time.

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Section: Discussionsupporting

confidence: 53%

Dynamics of lipidome in a colon simulator

Kråkström

Alves

Dickens

et al. 2022

Preprint

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“…However, it remains unknown whether enterotypes differ in their capacity to harvest energy from the diet. Moreover, it is not known whether intestinal transit time, which is linked to gut microbial composition, diversity, and metabolism [ 15 – 19 ], is a determinant of microbiota-dependent energy harvest in the gut. Therefore, we investigated whether gut microbial energy extraction, as reflected by dry stool energy density, was associated with intestinal transit time and microbiome community structures in 85 overweight adults.…”

Section: Introductionmentioning

confidence: 99%

Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes

et al. 2022

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Background It has been hypothesised that the gut microbiota causally affects obesity via its capacity to extract energy from the diet. Yet, evidence elucidating the role of particular human microbial community structures and determinants of microbiota-dependent energy harvest is lacking. Results Here, we investigated whether energy extraction from the diet in 85 overweight adults, estimated by dry stool energy density, was associated with intestinal transit time and variations in microbial community diversity and overall structure stratified as enterotypes. We hypothesised that a slower intestinal transit would allow for more energy extraction. However, opposite of what we expected, the stool energy density was positively associated with intestinal transit time. Stratifications into enterotypes showed that individuals with a Bacteroides enterotype (B-type) had significantly lower stool energy density, shorter intestinal transit times, and lower alpha-diversity compared to individuals with a Ruminococcaceae enterotype (R-type). The Prevotella (P-type) individuals appeared in between the B- and R-type. The differences in stool energy density between enterotypes were not explained by differences in habitual diet, intake of dietary fibre or faecal bacterial cell counts. However, the R-type individuals showed higher urinary and faecal levels of microbial-derived proteolytic metabolites compared to the B-type, suggesting increased colonic proteolysis in the R-type individuals. This could imply a less effective colonic energy extraction in the R-type individuals compared to the B-type individuals. Notably, the R-type had significantly lower body weight compared to the B-type. Conclusions Our findings suggest that gut microbial energy harvest is diversified among individuals by intestinal transit time and associated gut microbiome ecosystem variations. A better understanding of these associations could support the development of personalised nutrition and improved weight-loss strategies.

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“…Particularly dietary ber intake is considered to have a relevant role here because non-digestible carbohydrates are the precursors of SCFA (9). Another potential confounding factor that was not assessed in the current research is gut transit time (54). In addition, it should be noted that fecal and blood samples were not always collected on the same day, since blood sample analysis was part of standard care and depended on individual treatment schedules.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, it might be bene cial to include markers of gastrointestinal in ammation (e.g. fecal calprotectin) and gut transit time (54,55).…”

Section: Discussionmentioning

confidence: 99%

Fecal levels of SCFA and BCFA during capecitabine in patients with metastatic or unresectable colorectal cancer

Ziemons

Aarnoutse

Heuft

et al. 2023

Preprint

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Background Short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA) are produced by the gut microbiota and are considered to fulfill crucial physiological roles. Previous pre-clinical studies also indicated bi-directional interactions between gut bacteria and the chemotherapeutic capecitabine or its metabolite 5-FU. However, evidence from clinical studies in this field of research is scarce. This study investigated the effect of three cycles of capecitabine on fecal SCFA and BCFA levels and their associations with tumor response, nutritional status, physical performance, chemotherapy-induced toxicity, systemic inflammation, and bacterial abundances in patients with colorectal cancer (CRC). Methods Forty-four patients with metastatic or unresectable CRC, scheduled for treatment with capecitabine (± bevacizumab), were prospectively enrolled in a multicentre cohort study. Patients collected a fecal sample and completed a questionnaire before (T1), during (T2), and after (T3) three cycles of capecitabine. Tumor response (based on CT/MRI scans), nutritional status (MUST score), physical performance (Karnofsky Performance Score), and chemotherapy-induced toxicity (CTCAE) were recorded. Additional data on clinical characteristics, treatment regimen, medical history, and blood inflammatory parameters were collected. Fecal SCFA and BCFA concentrations were determined by gas chromatography-mass spectrometry (GC-MS). Gut microbiota composition was assessed using 16S rRNA amplicon sequencing. Results Fecal levels of the SCFA valerate and caproate decreased significantly during three cycles of capecitabine in our patient population. Furthermore, baseline levels of the BCFA iso-butyrate were associated with tumor response. Nutritional status, physical performance, and chemotherapy-induced toxicity were not statistically significantly associated with SCFA or BCFA. Baseline SCFA correlated positively with blood neutrophil counts. At the three sampling timepoints, we identified associations between SCFA and BCFA and the relative abundance of bacterial taxa on family level. Conclusions The present study provided the first indications for a role of SCFA and BCFA during treatment with capecitabine as well as implications and recommendations for further research. More knowledge in this field will contribute to the evidence-based design of interventions targeting the gut microbiota and/or SCFA/BCFA production to optimize chemotherapy efficacy. Trial registration The current study was registered in the Dutch Trial Register (NTR6957) on 17/01/2018 and can be consulted via the International Clinical Trial Registry Platform (ICTRP).

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Advancing human gut microbiota research by considering gut transit time

Cited by 109 publications

References 226 publications

Dynamics of lipidome in a colon simulator

Dynamics of lipidome in a colon simulator

Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes

Fecal levels of SCFA and BCFA during capecitabine in patients with metastatic or unresectable colorectal cancer

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