[Literature library] Complexity in HMO mixture composition and gut ecosystem

Study design

In vitro models

• Baby M-SHIME^®: to mimic the microbial ecosystem
• Caco-2 / HT29-MTX co-culture: to mimic the intestinal epithelium
   

Control condition

• Baseline values after 14-day fecal inocula stabilization before treatment period
   

Treatment groups

• Lactose
• 2’-FL
• 2’-FL + LNnT
• A mixture of 6 HMOs (6-HMO): 2’-FL, LNT, LNnT, DFL, 3’-SL, 6’-SL
   

Results

Bifidogenic environment and metabolic shift

• Only 2’-FL + LNnT and 6-HMO increased bifidobacteria levels when compared to the control condition
• All HMO groups promote short-chain fatty acid (SCFA) production when compared to baseline, without increasing gas level
   

Microbial modulation in luminal compartment

• HMOs demonstrated distinct impacts on various gut microbiota members
  • 2’-FL increased levels of Bifidobacteriaceae (Bifidobacterium) and Coriobacteriaceae (Collinsella)
  • 2’-FL + LNnT increased level of Brucellaceae (Ochrobactrum)
  • 6-HMO increased level of Ruminococcaceae (Faecalibacterium)
• All HMO groups demonstrated a consistent effect of reducing the Veillonellaceae family, which was particularly observed in the distal colon 6-HMO treated reactor across the 3-week treatment
• Increase in Bifidobacteriaceae and Ruminococcaceae levels were specific for 6-HMO, which was the only treatment that showed an increase in Bacteroidaceae levels from the 2^nd week of treatment until the end of the assay
• Specific operational taxonomic unit (OTU) enrichment in the luminal compartment depended on the treatment
  • Lactose enriched OTU1 (Megamonas sp.), OTU2 (Bifidobacterium longum) and OTU31 (Allistipes finegoldi)
  • 2’-FL was associated with high abundance of OTU3 (Bifidobacterium adolescentis), OTU29 (Collinsella aerofaciens) and OTU38 (Sutterella sp.)
  • 2’-FL + LNnT enriched OTU36 (Clostridium sp.)
  • 6-HMO predominantly and consistently enriched OTU20 (Faecalibacterium prausnitzii) and OTU35 (Bifidobacterium dentium)
     

Microbial modulation in mucosal compartment

• 2’-FL + LNnT and 6-HMO had a consistent and strong effects of reducing Megamonas abundance at the genus level after the second week of the treatment
• At OTU level,
  • Lactose showed enrichment in OTU2 (Bifidobacterium longum) and OTU7 (Clostridium clostridioforme)
  • 2’-FL showed enrichment in OTU29 (Collinsella aerofaciens) and OTU31 (Allistipes finegoldi)
  • 2’-FL + LNnT showed enrichment in OTU9 (Bifidobacterium bifidum) and OTU36 (Clostridium sp.)
  • 6-HMO showed enrichment in OTU10 (Roseburia inulinivorans) and OTU63 (Ruminococcus lactaris)
• 6-HMO demonstrated the fastest and highest bifidogenic potential overall
   

Protection of intestinal barrier from a pro-inflammatory challenge

• Before the pro-inflammatory challenge, incubation with 6-HMO supernatants showed significantly higher mean trans-epithelial electrical resistance (TEER) values than in control cells (Refer to fresh, unfermented culture SHIME^® media)
• After the pro-inflammatory challenge, TEER drop was significantly prevented by incubation with supernatants from Baby M-SHIME^® dosed with 2’-FL + LNnT and 6-HMO
• FD4 assay further confirmed the protective effect of HMOs on intestinal barrier functions against pro-inflammatory challenge
   

Conclusion

The study suggests that increasing the complexity of HMO composition would be beneficial to the developing infants’ gut ecology as:

• Bifidobacterial communities may be promoted
• The gut barrier may be protected from pro-inflammatory imbalances
   

Abbreviations
2’-FL = 2’-Fucosyllactose; LNnT = Lacto-N-Neotetraose; LNT = Lacto-N-Tetraose; DFL = Difucosyllactose; 3’-SL = 3’-Sialyllactose; 6’-SL = 6’-Sialyllactose
 

Link to the full article:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227761/pdf/nutrients-14-02546.pdf
 

Reference:

Natividad JM et al. Human milk oligosaccharides and lactose differentially affect infant gut microbiota and intestinal barrier in vitro. Nutrients. 2022;14(12):2546.
 

Other articles that you might be interested in:

• [Infographic] HMO Diversity
• [Video] Understanding Human Milk Oligosaccharides (HMOs) Diversity in Human Milk – Ms. Jodi Bettler
   

WYE-EM-092-JUL-22