Safety and functional enrichment of gut microbiome in healthy subjects consuming a multi-strain fermented milk product: a randomised controlled trial

Abstract

Many clinical studies have evaluated the effect of probiotics, but only a few have assessed their dose effects on gut microbiota and host. We conducted a randomized, double-blind, controlled intervention clinical trial to assess the safety (primary endpoint) of and gut microbiota response (secondary endpoint) to the daily ingestion for 4 weeks of two doses (1 or 3 bottles/day) of a fermented milk product (Test) in 96 healthy adults. The Test product is a multi-strain fermented milk product, combining yogurt strains and probiotic candidate strains Lactobacillus paracasei subsp. paracasei CNCM I-1518 and CNCM I-3689 and Lactobacillus rhamnosus CNCM I-3690. We assessed the safety of the Test product on the following parameters: adverse events, vital signs, hematological and metabolic profile, hepatic, kidney or thyroid function, inflammatory markers, bowel habits and digestive symptoms. We explored the longitudinal gut microbiota response to product consumption and dose, by 16S rRNA gene sequencing and functional contribution by shotgun metagenomics. Safety results did not show any significant difference between the Test and Control products whatever the parameters assessed, at the two doses ingested daily over a 4-week-period. Probiotic candidate strains were detected only during consumption period, and at a significantly higher level for the three strains in subjects who consumed 3 products bottles/day. The global structure of the gut microbiota as assessed by alpha and beta-diversity, was not altered by consumption of the product for four weeks. A zero-inflated beta regression model with random effects (ZIBR) identified a few bacterial genera with differential responses to test product consumption dose compared to control. Shotgun metagenomics analysis revealed a functional contribution to the gut microbiome of probiotic candidates.

A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Helicobacter pylori Therapy

“…Overall, the Test product affected gut microbiota mostly during the recovery phase following Hp treatment. Also, the Test product effect seemed more pronounced in the present study in case of microbiota alteration than in healthy subjects not exposed to antibiotics as previously reported [ 20 ].…”

“…A dairy product containing the strain Lacticaseibacillus paracasei ( Lp ) CNCM I-1518 was previously shown to reduce both antibiotic associated diarrhea (AAD) and Cd -associated diarrhea (CDAD) occurrence in hospitalized elderly [ 17 , 18 ] and to increase the Hp eradication rate in children [ 19 ]. Recently, a seven-strain fermented milk product containing Lp CNCM I-1518, Lp CNCM I-3689, Lacticaseibacillus rhamnosus ( Lr ) CNCM I-3690, and yogurt strains, was shown to be safe in healthy subjects [ 20 ].…”

Probiotic Yeasts and Vibrio anguillarum Infection Modify the Microbiome of Zebrafish Larvae

“…The lower colonization capacity (CFU/larvae) of Y. lipolytica 242 observed in Tg(Bacmpx:GFP) i114 , compared to D. hansenii 97, could explain their lower protection effect. This highlights the importance of the dose on probiotic effects, as recently reported (Alvarez et al, 2020). The dose must be adjusted not only considering the probiotic strain but also the host target and disease context.…”

Colonization Ability and Impact on Human Gut Microbiota of Foodborne Microbes From Traditional or Probiotic-Added Fermented Foods: A Systematic Review

“…The analysis of gut microbiota composition was performed using different methods, which were often applied in combination. Three studies analyzed microbiota variations through 16S rRNA based or whole genome shotgun metagenomics ( 44 , 47 , 48 ) allowing detection of all microbial groups, while qPCR was used to evaluate the presence of specific microbial groups ( 45 , 48 ). NGS was performed on V3–V4 ( n = 2) or V4–V5 ( n = 1) variable regions of the 16S rRNA gene.…”

“…On the other hand, conflicting results were obtained at the level of gut bifidobacterial species, which were reported to increase ( 49 ), decrease ( 47 ), or remain unaffected ( 52 ). One study reported that, while gut microbiota structure was modestly modified after consumption, a few genera corresponding to Lactobacillus, Holdemania , and Clostridiales were differentially affected in response to different doses of ingested probiotic food ( 44 ). Finally, 2 studies reported no significant changes in the overall composition of gut microbiota following fermented milk ingestion ( 50 , 51 ).…”