Encapsulated Probiotics & Gut Microbiota

Official title

A Physiological Study of a Fermented Yogurt Drink Containing Probiotics

Overview

The aim of this study is to determine whether encapsulation of probiotic bacteria using natural plant protein can enhance bacterial colonisation. Lactobacillus rhamnosus is an ideal strain for the intervention, as it has been shown to affect overall gut health, gut-brain axis, and brain function. Twenty-five participants aged 25 to 65 years will be recruited and assessed on four occasions to compare the blood and faecal effects of a 28-day ingestion of a yoghurt beverage with and without the probiotic strain of interest. The study window will be 70+/13 days. The current study will provide important information on the physiological function of probiotics in the small bowel. Understanding the underlying physiological effects of targeted probiotic delivery to the intestine and the impact on the microbiome is important for health outcomes.

Detailed description

The investigators plan to assess the gut microbiome and changes in probiotic diversity at the end of a course of a beverage containing encapsulated Lacticaseibacillus rhamnosus, compared to those at the end of a course of the same beverage without probiotics.

This is a randomised, double-blinded, placebo-controlled crossover study. Twenty-five healthy men and women with a body mass index (BMI) between 18.5-31.9 kg/m2, aged 25-65 years, will be recruited and randomised to a commercial fermented (yoghurt) drink containing a) encapsulated probiotics consisting of Lacticaseibacillus rhamnosus, or b) a non-probiotic fermented (yoghurt) dairy drink (control). The number of participants includes a 10% drop-out rate.

Each participant will be studied on four occasions in random order following a crossover design. Each will receive a 200 ml beverage containing yoghurt per day for 28 days, either a) fortified with 1 billion probiotics contained in pea protein capsules or b) the control beverage (same yoghurt without probiotic). Faecal samples will be collected on four occasions: at baseline, and at 28, 42 and 70 days after baseline.

The current study will provide important information on the physiological function of probiotics in metabolic and inflammatory biochemical parameters, as well as in their capacity to colonise the gastrointestinal tract.

Interventions

• Biological probiotic containing L.rhamnosus R0011 strain
  Twenty-five participants will be studied on four occasions in random order and in a crossover design. Subjects will receive a daily dose of 200 ml on two different occasions for 28 days, a commercial dairy drink fortified with 1Billion probiotics in the pea protein capsules. Feacal samples will be collected on four occasions: at baseline, 28 days after baseline, 42 days and 70 days after baseline.
• Dietary supplement 200 ml yogurt drink
  Twenty-five participants will be studied on four occasions in random order and in a crossover design. Subjects will receive a daily dose 200 ml on two different occasions for 28 days, a commercial dairy drink (no probiotics). Feacal samples will be collected on four occasions: at baseline, 28 days after baseline, 42 days and 70 days after baseline.

Primary outcome measures

• Colonisation [Time frame: 28 days]

Eligibility criteria

Inclusion criteria

• Capacity to obtain and sign informed consent before any study-related procedure
• BMI range 18.5-31.9 kg/m2
• Willing to abstain from regular consumption of probiotic supplements or food products containing probiotic bacteria (including fermented food and beverages).
• Willing to abstain from regular consumption of supplements and medications known to alter gastrointestinal function or inflammatory status during the study.

Exclusion criteria

Participants who meet any of the following criteria will be excluded:

• Smoking
• Substance abuse
• Pregnancy
• Diagnosis of type 1 and/or type 2 diabetes
• Current (or within the last 4 weeks prior to study start) use of probiotic supplementation.
• Immobile (defined as the inability to participate in all study-related procedures)
• History of complicated gastrointestinal surgery
• Diagnosed with inflammatory bowel disease (IBD)
• Current diagnosis of psychiatric disease/s or syndromes
• Current diagnosis of neurodegenerative disease
• Systemic use of antibiotics and/or steroid medication in the last 4 months prior to inclusion
• Use of any non-steroidal anti-inflammatory drug (NSAID) more than 3 times a week for the last 2 months
• Consumption of any NSAID within 7 days of study start
• Any condition which could substantially interfere with intestinal barrier function (e.g. gluten sensitivity, lactose intolerance, celiac disease, IBS, IBD) or in any other way with the outcome of the study, as decided by the principal investigator's discretion
• Regular smoking, use of snuff, nicotine, cannabidiol narcotics/supplements, or e-cigarette use
• Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion
• Regular use, for more than three times a week for the last 2 months and/or 7 days prior to inclusion, of medications which, according to the principal investigator, can have an anti-inflammatory effect or affect in any way the intestinal barrier function or have an impact on the study analysis (such as laxatives, anti-diarrheal, anti-cholinergic, etc.)
• After being included in the study, starting any medication or treatment that could potentially influence the study participation and/or study analysis.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Zhou JS, Shu Q, Rutherfurd KJ, Prasad J, Gopal PK, Gill HS. Acute oral toxicity and bacterial translocation studies on potentially probiotic strains of lactic acid bacteria. Food Chem Toxicol. 2000 Feb-Mar;38(2-3):153-61. doi: 10.1016/s0278-6915(99)00154-4. PMID 10717355
• Zhou JS, Shu Q, Rutherfurd KJ, Prasad J, Birtles MJ, Gopal PK, Gill HS. Safety assessment of potential probiotic lactic acid bacterial strains Lactobacillus rhamnosus HN001, Lb. acidophilus HN017, and Bifidobacterium lactis HN019 in BALB/c mice. Int J Food Microbiol. 2000 May 25;56(1):87-96. doi: 10.1016/s0168-1605(00)00219-1. PMID 10857928
• Zhou JS, Pillidge CJ, Gopal PK, Gill HS. Antibiotic susceptibility profiles of new probiotic Lactobacillus and Bifidobacterium strains. Int J Food Microbiol. 2005 Feb 1;98(2):211-7. doi: 10.1016/j.ijfoodmicro.2004.05.011. PMID 15681048
• Zheng Y, Yu Z, Zhang W, Sun T. Lactobacillus rhamnosus Probio-M9 Improves the Quality of Life in Stressed Adults by Gut Microbiota. Foods. 2021 Oct 8;10(10):2384. doi: 10.3390/foods10102384. PMID 34681433
• Zahr NM, Mayer D, Pfefferbaum A, Sullivan EV. Low striatal glutamate levels underlie cognitive decline in the elderly: evidence from in vivo molecular spectroscopy. Cereb Cortex. 2008 Oct;18(10):2241-50. doi: 10.1093/cercor/bhm250. Epub 2008 Jan 29. PMID 18234683
• Yao M, Xie J, Du H, McClements DJ, Xiao H, Li L. Progress in microencapsulation of probiotics: A review. Compr Rev Food Sci Food Saf. 2020 Mar;19(2):857-874. doi: 10.1111/1541-4337.12532. Epub 2020 Feb 11. PMID 33325164
• Wu D, Lewis ED, Pae M, Meydani SN. Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance. Front Immunol. 2019 Jan 15;9:3160. doi: 10.3389/fimmu.2018.03160. eCollection 2018. PMID 30697214
• World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available. PMID 24141714

Identifiers

NCT: NCT07439978 · REF No. RS26-013

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗