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Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation.

ABSTRACT: Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, n = 2507; ZOE PREDICT-1, n = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average h²: serum = 14%(SD = 14%); stool = 12%(SD = 6%)). Furthermore, we find that gut microbiome can accurately predict their fecal levels (AUC>0.71) while presenting weaker associations with serum. Finally, we report different correlation patterns with inflammatory markers depending on the type of inflammatory response (chronic or acute trauma). Our results illustrate the breadth of the physiological relevance of SCFAs on human inflammatory and metabolic responses highlighting the need for a deeper understanding of this important class of molecules.

SUBMITTER: Nogal A

PROVIDER: S-EPMC10395212 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature

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Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation.

Nogal Ana A Asnicar Francesco F Vijay Amrita A Kouraki Afroditi A Visconti Alessia A Louca Panayiotis P Wong Kari K Baleanu Andrei-Florin AF Giordano Francesca F Wolf Jonathan J Hadjigeorgiou George G Davies Richard R Michelotti Gregory A GA Franks Paul W PW Berry Sarah E SE Falchi Mario M Ikram Adeel A Ollivere Benjamin J BJ Zheng Amy A Nightingale Jessica J Mangino Massimo M Segata Nicola N Bulsiewicz William J WJ Spector Tim D TD Valdes Ana M AM Menni Cristina C

Gut microbes 20230101 1

Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, <i>n</i> = 2507; ZOE PREDICT-1, <i>n</i> = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, signi ...[more]

PMID: 37526398

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Project description:The gut microbiome has combined with other person-specific information, such as blood parameters, dietary habits, anthropometrics, and physical activity been found to predict personalized postprandial glucose responses (PPGRs) to various foods. Yet, the contributions of specific microbiome taxa, measures of fermentation, and abiotic factors in the colon to glycemic control remain elusive. We tested whether PPGRs 60 min after a standardized breakfast was associated with gut microbial α-diversity (primary outcome) and explored whether postprandial responses of glucose and insulin were associated with specific microbiome taxa, colonic fermentation as reflected by fecal short-chain fatty acids (SCFAs), and breath hydrogen and methane exhalation, as well as abiotic factors including fecal pH, fecal water content, fecal energy density, intestinal transit time (ITT), and stool consistency. A single-arm meal trial was conducted. A total of 31 healthy (24 female and seven male) subjects consumed a standardized evening meal and a subsequent standardized breakfast (1,499 kJ) where blood was collected for analysis of postprandial glucose and insulin responses. PPGRs to the same breakfast varied across the healthy subjects. The largest inter-individual variability in PPGRs was observed 60 min after the meal but was not associated with gut microbial α-diversity. In addition, no significant associations were observed between postprandial responses and specific taxa of the gut microbiome, measures of colonic fermentation, ITT, or other abiotic factors. However, fasting glucose concentrations were negatively associated with ITT, and fasting insulin was positively associated with fasting breath hydrogen. In conclusion, the gut microbiome, measures of colonic fermentation, and abiotic factors were not shown to be significantly associated with variability in postprandial responses, suggesting that contributions of the gut microbiome, colonic fermentation, and abiotic factors to PPGRs may be subtle in healthy adults.

Project description:In ruminants, the digestion and utilization of dietary proteins are closely linked to the bacterial populations that are present in the gastrointestinal tract. In the present study, 16S rDNA sequencing, together with a metagenomic strategy was used to characterize the fecal bacteria of ewes in the early lactation stage after feeding with three levels of dietary proteins 8.58%, 10.34%, and 13.93%, in three different groups (H_1), (H_m) and (H_h), respectively. A total of 376,278,516 clean data-points were obtained by metagenomic sequencing. Firmicutes and Bacteroidetes were the dominant phyla, regardless of the dietary protein levels. In the H_h group, the phyla Proteobacteria, Caldiserica, and Candidatus_Cryosericota were less abundant than those in the H_I group. In contrast, Lentisphaerae, Chlamydiae, and Planctomycetes were significantly more abundant in the H_h group. Some genera, such as Prevotella, Roseburia, and Firmicutes_unclassified, were less abundant in the H_h group than those in the H_I group. In contrast, Ruminococcus, Ruminococcaceae_noname, Anaerotruncus, Thermotalae, Lentisphaerae_noname, and Paraprevotella were enriched in the H_h group. The acquired microbial genes were mainly clustered into biological processes; molecular functions; cytosol; cellular components; cytoplasm; structural constituents of ribosomes; plasma membranes; translation; and catalytic activities. 205987 genes were significantly enriched in the H_h group. In contrast, 108129 genes were more abundant in the H_I group. Our findings reveal that dynamic changes in fecal bacteria and their genes are strongly influenced by the levels of dietary proteins. We discovered that differentially expressed genes mainly regulate metabolic activity and KEGG demonstrated the primary involvement of these genes in the metabolism of carbohydrates, amino acids, nucleotides, and vitamins. Additionally, genes responsible for metabolism were more abundant in the H_h group. Investigating fecal bacterial characteristics may help researchers develop a dietary formula for lactating ewes to optimize the growth and health of ewes and lambs.

Project description:BackgroundGut bacteria-derived short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA) are considered to have beneficial metabolic, anti-inflammatory as well as anti-carcinogenic effects. Previous preclinical studies indicated bidirectional interactions between gut bacteria and the chemotherapeutic capecitabine or its metabolite 5-FU. 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).MethodsForty-four patients with metastatic or unresectable CRC, scheduled for treatment with capecitabine (± bevacizumab), were prospectively enrolled. Patients collected a fecal sample and completed a questionnaire before (T1), during (T2) and after (T3) three cycles of capecitabine. Tumor response (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.ResultsFecal levels of the SCFA valerate and caproate decreased significantly during three cycles of capecitabine. Furthermore, baseline levels of the BCFA iso-butyrate were associated with tumor response. Nutritional status, physical performance and chemotherapy-induced toxicity were not significantly associated with SCFA or BCFA. Baseline SCFA correlated positively with blood neutrophil counts. At all time points, we identified associations between SCFA and BCFA and the relative abundance of bacterial taxa on family level.ConclusionsThe present study provided first indications for a potential role of SCFA and BCFA during capecitabine treatment as well as implications for further research.Trial registrationThe 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).

Dataset Information

Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation.

Publications

Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation.

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