Serum-Derived Bovine Immunoglobulin Stimulates SCFA Production by Specific Microbes in the Ex Vivo SIFR® Technology

Abstract

Serum-derived bovine immunoglobulins (SBI) exert health benefits mediated by their ability to bind microbial components, thereby preventing translocation and subsequent inflammation. While in vivo studies have shown that a fraction of SBI also reaches the colon, little is known about the impact of SBI on the dense colonic microbiota that has great potential to impact human health. This study, therefore, investigated the impact of three bovine plasma protein fractions (SBI, bovine plasma (BP) and albumin-enriched bovine plasma (ABP)) on the gut microbiota of six human adults using the novel ex vivo SIFR® technology, recently demonstrated to generate predictive findings for clinical studies. When dosed at an equivalent of 5 g/day, all protein fractions significantly increased health-related metabolites—acetate, propionate, and butyrate. Upon simulating small intestinal absorption, SBI still markedly increased acetate and propionate, demonstrating that SBI is more resistant to small intestinal digestion and absorption compared to the other protein sources. Despite noticeable interindividual differences in microbiota composition among human adults, SBI consistently stimulated a narrow spectrum of gut microbes, which largely differed from the ones that are typically involved in carbohydrate fermentation. The SBI-fermenting consortium included B. vulgatus and L. edouardi (correlating with acetate and propionate) along with Dorea longicatena, Coprococcus comes and the butyrate-producing bacterium SS3/4 (correlating with butyrate). Overall, this study revealed that protein bovine fractions can contribute to health benefits by specifically modulating the human gut microbiota. While health benefits could follow from the production of SCFA, a broader range of protein-derived metabolites could also be produced. This study also confirms that the concept of prebiotics (substrates selectively utilized by host microorganisms conferring a health benefit) could go beyond the use of ingestible carbohydrates and extend to partially indigestible proteins.

Lacticaseibacillus rhamnosus ATCC 53103 and Limosilactobacillus reuteri ATCC 53608 Synergistically Boost Butyrate Levels upon Tributyrin Administration Ex Vivo

“…Nevertheless, other lactate-utilizing, butyrate-producing species such as Anaerobutyricum hallii were also consistently detected in the microbiota of each of the six donors at baseline levels (0.8 ± 0.1%) that even exceeded those of C. catus (0.4 ± 0.2%). While A. hallii strongly increased and correlated with butyrate production upon inulin and 2′FL treatment in previous SIFR ® studies [ 37 ], A. hallii was unaffected by TB + REU/LGG treatment in the current study, further highlighting the remarkable complementarity between C. catus and REU/LGG in the presence of TB. As a potential explanation, Sheridan et al (2022) recently demonstrated that glucose partially repressed lactate utilization ( lct ) cluster expression in A. soehngenii (another lactate-consuming, butyrate-producing species), while such repression was not observed for C. catus [ 46 ].…”

“…A PCA based on fundamental fermentation parameters (pH, gas production, SCFA, bCFA) ( Figure 3 A) provided comprehensive insight into overall treatment effects as the first two components explained 92.4% of the variation of the dataset. There was a marked differential clustering of 0 h and 48 h samples, reflecting the strong production of acetate, propionate, butyrate, bCFA, and gasses between 0 and 48 h. The expansion of a complex gut microbiota over the duration of the experiment is a core aspect of the ex vivo SIFR ® technology [ 37 ].…”

“…This study evaluated the potential to manage butyrate supply to the host via tributyrin oil (TB), whether or not co-supplemented with a Lactobacillaceae species (REU or LGG). The research question was addressed using the ex vivo SIFR ® technology, a recently developed gut model that, within 24–48 h, provides insights into gut microbiota modulation that are predictive for observations of repeated-intake clinical studies (down to species level resolution) [ 37 ]. In line with the aforementioned study, a high technical reproducibility, marked metabolite production, high microbial diversity, and, most importantly, sustained similarity between the original donor microbiota and untreated SIFR ® reactors at 48 h was observed during the current study.…”

“…While a key advantage of the SIFR ® technology is the absence of a host component, enabling unique insights into metabolite production and microbial composition that are hard to obtain in vivo, a related drawback is that findings of such ex vivo studies should be regarded as complementary to in vivo studies, rather than as a potential replacement of clinical studies. Despite the high predictivity of the SIFR ® technology for clinical findings [ 37 ], clinical studies are required to demonstrate potential health benefits for the host upon TB and LGG/REU co-supplementation.…”

“…Further, both strains are of particular interest, as on the one hand, LGG is the most documented probiotic strain [ 35 ], while REU has been demonstrated to convert glycerol to reuterin, an antimicrobial compound [ 36 ], thus providing an additional unique mechanism for microbiota modulation upon tributyrin (and thus also glycerol) intake. The research question was addressed using the ex vivo SIFR ® (Systemic Intestinal Fermentation Research) technology [ 37 ]. The SIFR ® technology is a highly reproducible gut model that accurately preserves in vivo-derived microbiota throughout the entire duration of the experiment.…”