Prebiotics for Lactose Intolerance: Variability in Galacto-Oligosaccharide Utilization by Intestinal Lactobacillus rhamnosus

Abstract

Lactose intolerance, characterized by a decrease in host lactase expression, affects approximately 75% of the world population. Galacto-oligosaccharides (GOS) are prebiotics that have been shown to alleviate symptoms of lactose intolerance and to modulate the intestinal microbiota, promoting the growth of beneficial microorganisms. We hypothesized that mechanisms of GOS utilization by intestinal bacteria are variable, impacting efficacy and response, with differences occurring at the strain level. This study aimed to determine the mechanisms by which human-derived Lactobacillus rhamnosus strains metabolize GOS. Genomic comparisons between strains revealed differences in carbohydrate utilization components, including transporters, enzymes for degradation, and transcriptional regulation, despite a high overall sequence identity (>95%) between strains. Physiological and transcriptomics analyses showed distinct differences in carbohydrate metabolism profiles and GOS utilization between strains. A putative operon responsible for GOS utilization was identified and characterized by genetic disruption of the 6-phospho-β-galactosidase, which had a critical role in GOS utilization. Our findings highlight the importance of strain-specific bacterial metabolism in the selection of probiotics and synbiotics to alleviate symptoms of gastrointestinal disorders including lactose intolerance.

The pleiotropic effects of prebiotic galacto-oligosaccharides on the aging gut

“…A previous in vitro study showed that butyrate stimulated expression of Lgals1 in the HT29-C1.16E, a clonal derivative of the HT29 human colonic cells [100]. As extensively reported, GOS fermentation by intestinal microorganisms results, via cross-feeding events, in the generation of short chain fatty acids (SCFAs) [95], which directly influence host intestinal physiology [98,124]. SCFAs including butyrate are utilized by intestinal epithelial cells as an energy source, promoting host epithelial metabolism [125], and can also be used as signaling molecules, influencing host inflammation [98,126], stem cell proliferation [127], and barrier integrity [99,126].…”

“…GOS administration resulted in increased the abundance of both β-galactosidases and β-glucosidases in young and old animals. GOS are broken down by bacterial enzymes, producing short-chain fatty acids including lactate and acetate [95]. In the healthy adult gut, secondary degraders including Faecalibacterium [96] and Roseburia [97] utilize these primary fermentation products to generate butyrate, which directly benefits host physiology [98][99][100].…”

In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes

“…Apart from potentially being able to complement the microbiome, microbes from fermented foods may also produce or consume compounds with relevance to human health or provide substrates for the resident gut microbiome, leading to metabolites that in turn affect the health of the host. For instance, some Lactobacillus strains such as L. rhamnosus can digest lactose, which may be advantageous for lactose intolerant individuals [ 21 ]. Some LABs can produce folate (vitamin B9), which is a particularly relevant nutrient for pregnant women, as it can help to prevent birth defects such as spina bifida [ 22 ].…”

The Biotherapeutic Potential of Lactobacillus reuteri Characterized Using a Target-Specific Selection Process

“…The ability to use lactose as the growth substrate was tested by inoculating washed pure suspensions of L. reuteri DSM 17938, L. rhamnosus ATCC 53103, and L. reuteri LMG P-2748 in MRS medium without dextrose, containing either 1% glucose or 1% lactose as the sole carbon source (Arnold et al, 2018). After being incubated for 18 h in microaerophilic conditions at 37 • C, live bacteria were enumerated by seeding decimal dilution of the cultures on MRS agarose plates.…”