Modulation of Secondary Bile Acids Through the Intestinal Microbiota After Consumption of a High-protein Diet.

Healthy Clinical Trial

Official title:

Modulation of Secondary Bile Acids Through the Intestinal Microbiota After Consumption of a High-protein Diet.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05906641
• Other study ID #: 4532
• Status: Completed
• Phase: N/A
• Start date: August 1, 2023
• Est. completion date: December 30, 2023

Study information

• Verified date: March 2024
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate whether changes in the gut microbiota generated after the consumption of a high protein diet in healthy subjects, modify the production of secondary bile acids. In addition, it will be seen whether a high protein intake modifies postprandial glucose response and its relationship with gut microbiota composition.

Description:

The gut microbiota is a set of microorganisms that inhabit the human digestive tract and are fundamental for the health of the host. Among the functions of the gut microbiota is the production of metabolites, such as the production of secondary bile acids from primary bile acids. On the other hand, evidence has shown that the amount of protein intake can modify the composition of the gut microbiota and in turn it increase the concentration of secondary biles acids in animal models. In addition, the consumption of a high-protein diet has been related to a decrease in postprandial glucose concentrations. Therefore, the aim of this study is to evaluate changes in secondary bile acids concentration derived from gut microbiota after the consumption of a high-protein diet in healthy subjects. Subjects with a BMI between 18.5 and 24.9 kg/m2 will be selected and will be continuously monitored with a continuous glucose monitor through 15 days. During the first 7 days participants will follow an isocaloric diet (50% carbohydrates, 30% fat and 20% protein), while during the last 7 days participants will receive an intervention with a supplement of protein (calcium caseinate) which will increase their protein intake to 30% of the total energy requirement. At the initial and final visit, blood samples will be taken for determination of biochemical parameters, amino acids and primary bile acids and a stool sample will be requested for sequencing gut microbiota and determined secondary bile acids.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 30, 2023
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female.

• Between 18 and older

• BMI = 18.5 and = 24.9 kg/m2.

• Healthy

• Willing and able to sign written informed consent prior to trial entry

Exclusion Criteria:

• Have previously diagnosed with any chronic disease

• Patients with high blood pressure.

• Patients who have suffered a cardiovascular event.

• Patients with gastrointestinal diseases.

• Weight loss > 3 kg in the last 3 months.

• Catabolic diseases such as cancer and acquired immunodeficiency syndrome.

• Pregnancy status.

• Antibiotic consumption 3 months prior to the study.

• Be an undergraduate or graduate student within the Institute.

• Subjects with creatinine > 1.3 mg/dL for men and >1 mg/dL for women and ureic nitrogen > 20 mg/dL.

• Positive smoking.

• Drug treatment:

1. Antihypertensive drugs or treatment

2. Treatment with hypoglycemic agents or insulin and antidiabetic drugs.

3. Treatment with statins, fibrates or other drugs to control dyslipidemia.

4. Use of antibiotics in the three months prior to the study.

5. Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy.

6. Anorexigenic or that accelerate weight loss such as sibutramine or orlistat.

7. Probiotic, prebiotic or symbiotic supplements.

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• High-protein diet
Protein intake will be increased to be 30% calories from protein with calcium caseinate.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran	Mexico City

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Country where clinical trial is conducted

Mexico, 

References & Publications (13)

de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013 May 7;17(5):657-69. doi: 10.1016/j.cmet.2013.03.013. Epub 2013 Apr 18. — View Citation

FOLCH J, LEES M, SLOANE STANLEY GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497-509. No abstract available. — View Citation

Guzior DV, Quinn RA. Review: microbial transformations of human bile acids. Microbiome. 2021 Jun 14;9(1):140. doi: 10.1186/s40168-021-01101-1. — View Citation

Keller S, Jahreis G. Determination of underivatised sterols and bile acid trimethyl silyl ether methyl esters by gas chromatography-mass spectrometry-single ion monitoring in faeces. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Dec 25;813(1-2):199- — View Citation

Kumar DP, Asgharpour A, Mirshahi F, Park SH, Liu S, Imai Y, Nadler JL, Grider JR, Murthy KS, Sanyal AJ. Activation of Transmembrane Bile Acid Receptor TGR5 Modulates Pancreatic Islet alpha Cells to Promote Glucose Homeostasis. J Biol Chem. 2016 Mar 25;291 — View Citation

Murphy EA, Velazquez KT, Herbert KM. Influence of high-fat diet on gut microbiota: a driving force for chronic disease risk. Curr Opin Clin Nutr Metab Care. 2015 Sep;18(5):515-20. doi: 10.1097/MCO.0000000000000209. — View Citation

Pak HH, Cummings NE, Green CL, Brinkman JA, Yu D, Tomasiewicz JL, Yang SE, Boyle C, Konon EN, Ong IM, Lamming DW. The Metabolic Response to a Low Amino Acid Diet is Independent of Diet-Induced Shifts in the Composition of the Gut Microbiome. Sci Rep. 2019 — View Citation

Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, Abrouk M, Farahnik B, Nakamura M, Zhu TH, Bhutani T, Liao W. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017 Apr 8;15(1):73. doi: 10.1186/s12967-017-1175-y. — View Citation

Tirosh A, Calay ES, Tuncman G, Claiborn KC, Inouye KE, Eguchi K, Alcala M, Rathaus M, Hollander KS, Ron I, Livne R, Heianza Y, Qi L, Shai I, Garg R, Hotamisligil GS. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing — View Citation

Van Elswyk ME, Weatherford CA, McNeill SH. A Systematic Review of Renal Health in Healthy Individuals Associated with Protein Intake above the US Recommended Daily Allowance in Randomized Controlled Trials and Observational Studies. Adv Nutr. 2018 Jul 1;9 — View Citation

Wei M, Huang F, Zhao L, Zhang Y, Yang W, Wang S, Li M, Han X, Ge K, Qu C, Rajani C, Xie G, Zheng X, Zhao A, Bian Z, Jia W. A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility. EBioMedicine. 2020 May;55:102766. doi: 10.1016/j — View Citation

Wu S, Bhat ZF, Gounder RS, Mohamed Ahmed IA, Al-Juhaimi FY, Ding Y, Bekhit AEA. Effect of Dietary Protein and Processing on Gut Microbiota-A Systematic Review. Nutrients. 2022 Jan 20;14(3):453. doi: 10.3390/nu14030453. — View Citation

Zhao X, Yang X, Hang HC. Chemoproteomic Analysis of Microbiota Metabolite-Protein Targets and Mechanisms. Biochemistry. 2022 Dec 20;61(24):2822-2834. doi: 10.1021/acs.biochem.1c00758. Epub 2022 Jan 6. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in faecal microbiota composition in response to high-protein diet	Changes to the faecal microbiota will be assessed on a high-protein diet compared to an isocaloric diet in a short period of time. Bacterial composition was measured by 16 ribosomal sequencing at baseline at day 7 and at the end of the second week. The relative change of each bacterial taxon was calculated based on the abundance of the given bacteria at baseline, at 7 days and after 14 days	baseline, 7 days and 14 days
Primary	Increase of secondary bile acids production	Increase in the concentrations of lithocholic acid and deoxycholic acid in feces (mg/g of feces) measured by the method gas chromatography represented with the units micromol.	baseline, 7 days and 14 days
Secondary	Regulation of postprandial glucose response	Change in interstitial glucose determined by a continuous glucose monitor (mg/dL) within two weeks.	14 days
Secondary	Increase in serum glucagon concentration	Change in serum glucagon concentration determined by ELISA (pg/mL)	Baseline, 7 days and 14 days
Secondary	Decrease in serum insulin concentration	Change in serum insulin concentration determined by ELISA (pg/mL)	Baseline, 7 days and 14 days