Lactulose Crystals Beneficially Affect Community Composition Along Entire Human Colon in Vitro, Resulting in Donor-Dependent Prebiotic Effects at Metabolic Level

Abstract

A validated in vitro gut model (i.e. SHIME®) was used to assess the effect of repeated daily administration of lactulose on microbial metabolic activity and community composition in different colonic areas, with the focus on interindividual differences among three human subjects. An initial rise in acetate and lactate levels was observed in the proximal colon after lactulose administration, which could be linked to an overall strong bifidogenic effect as well as higher Lactobacilli levels in donors 2 and 3. Particularly two operational taxonomic units (OTUs) related to Bifidobacterium adolescentis and Bifidobacterium longum increased with lactulose addition. The enhanced acetate and lactate production subsequently stimulated microbial species involved in cross-feeding interactions, resulting in the donor-dependent production of propionate and/or butyrate. Additionally, a reduction in markers of proteolytic fermentation was detected upon lactulose supplementation. A wide spectrum of propionate-and especially butyrate-producing microbes, such as the next-generation probiotics Faecalibacterium prausnitzii and Akkermansia muciniphila, were donor-dependently enhanced in the distal colon, which is of specific interest as many colonic diseases originate in the distal part of the colon. For the first time beneficial effects of lactulose on the microbiota as well as metabolic activity could be demonstrated over the entire colon in vitro.

Co-Administration of Lactulose Crystals with Amoxicillin Followed by Prolonged Lactulose Treatment Promotes Recovery of the Human Gut Microbiome In Vitro

“…This finding is in line with the observations of Ladirat et al [ 7 ] which showed that prebiotic intake stimulated recovery of Bifidobacterium species as well as butyrate-producing bacteria belonging to the Firmicutes phylum following amoxicillin treatment. Moreover, extended lactulose administration in our study resulted in increased abundance of Rikenellaceae in the DC, a finding that is supported by Duysburgh and co-workers [ 19 ]. Overall, these results indicate that administration of lactulose might be effective in restoring the gut microbiome following amoxicillin–clavulanic acid treatment by promoting Lactobacillus and Bifidobacterium species, which in turn could stimulate cross-feeding interactions.…”

“…Furthermore, several other health benefits have been reported for lactulose, including the stimulation of beneficial micro-organisms and inhibition of pathogenic bacteria along the gastrointestinal tract [ 14 , 15 ]. Recent in vitro studies revealed the prebiotic potential of lactulose, which was able to strongly enhance the abundance of health-promoting bifidobacteria and lactobacilli, as well as several other species, including Alistipes , Parabacteroides , Anaerostipes [ 16 , 17 ], Megasphaera [ 18 ] and the butyrate-producing Faecalibacterium prausnitzii [ 19 ]. In addition, Nikolaou et al [ 20 ] have shown that children treated with the antibiotic azithromycin in combination with lactulose showed faster recovery of intestinal homeostasis by stimulation of saccharolytic bacteria, such as Lactobacillus , Anaerostipes and Roseburia , providing evidence that lactulose could be an interesting compound for use in minimizing adverse effects induced by antibiotic therapy.…”

Long-Term Lactulose Administration Improves Dysbiosis Induced by Antibiotic and C. difficile in the PathoGutTM SHIME Model

“…Previous research showed a positive effect of lactulose supplementation on antibiotic-induced dysbiosis, increasing acetate and lactate levels, and promoting Bifidobacterium spp. growth [ 34 , 38 ].…”

“…In this study, we evaluated the effect of different long-term dosage regimens of lactulose on the instauration of CDI and C. difficile spore germination and recurrence using the in vitro PathoGut TM Simulator of the Human Intestinal Microbial Ecosystem (SHIME) model mimicking antibiotic-induced gut dysbiosis. As the proximal colon (PC) is the main colonic area of fermentation of lactulose [ 38 ], effects of repeated lactulose dosing on microbial metabolic activity and structure were specifically assessed in the PC area. However, CDI typically occurs in the distal colon (DC) region, as C. difficile is not able to germinate under acidic conditions [ 39 ].…”

Lacticaseibacillus rhamnosus GG and Saccharomyces cerevisiae boulardii supplementation exert protective effects on human gut microbiome following antibiotic administration in vitro

“…In vitro approaches (Minekus et al, 2014(Minekus et al, , 1999Molly et al, 1993) offer a suitable alternative as strict control of environmental factors allows evaluation of cross-talk between the indigenous microbial community and the probiotic strain(s) at the site of action. However, as intestinal models depend on human faecal samples to obtain a representative microbiome, it is important to account for inter-individual variation not only during in vivo, but also during in vitro trials (Duysburgh et al, 2019a).…”