A new approach of gut microbiota modulation by probiotic bacterial cells: formulation for use in metabolic endotoxemia
Bibliographic record
Abstract
The human gut microbiota plays an important role in the maintenance of human health. It forms a tremendous and complex bacterial bioreactor located in the human intestinal tract. An imbalance of the gut microbiota ecosystem, a state called gut dysbiosis, can disrupt the microbiota's functions. Endotoxins are immunogenic molecules produced by the gut microbiota that cause metabolic endotoxemia, a disorder characterized by low levels of circulating endotoxins that contribute to the development of many human diseases, including type 2 diabetes mellitus, obesity, and liver, cardiovascular, and inflammatory bowel diseases. Although many strategies have been developed to combate high dose endotoxemia such as in sepsis, none is available for use in metabolic endotoxemia. Thus, there is an urgent need for the development of an effective strategy for use in metabolic endotoxemia. In this thesis, the potential of a novel probiotic bacterial cells formulation to modulate the gut microbiota and reduce circulating endotoxtins was investigated in a series of in vitro and in vivo experiments. An in vitro human colonic microbiota model, easy to set up and that ensures long-term ecosystem stability, was developed. Probiotic bacteria - identified from the literature for their anti-inflammatory effects - were screened for colonic endotoxins reduction using the model. It was shown that Lactobacillus and Bifidobacterium strains modulated specifically colonic endotoxins concentrations, with Bifidobacterium longum subsp. infantis ATCC 15697 showing the highest reduction. B. infantis ATCC 15697 was further encapsulated within alginate-poly-L-lysine-alginate (APA) microcapsules and characterized for the colon targeted delivery of viable cells in flask studies and in a well-established human multistage gastrointestinal (GI) model. Results showed that APA microencapsulation delivery system significantly increased the cell survival of B. infantis ATCC 15697 to simulated human GI transit conditions, as well as enhanced the gut microbiota enrichment of loaded probiotic cells in the colon, as compared to the unencapsulated probiotic strain. The potential of the novel probiotic formulation to modulate the gut microbiota for use in metabolic endotoxemia was further tested in the human multistage GI model and in F344 rats. Results showed that APA microencapsulated B. infantis ATCC 15697 reduced colonic endotoxins concentrations through the modulation of gut bacterial populations and metabolites in in vitro and in vivo experiments. Importantly, orally administered APA microencapsulated B. infantis ATCC 15697 lowered circulating endotoxins in F344 rats. Thus, this thesis work demonstrates the significant potential of APA microencapsulated B. infantis ATCC 15697 probiotic bacterial cells to modulate the gut microbiota and reduce circulating endotoxins for use in metabolic endotoxemia. Further studies are required to investigate the safety and potentials of the formulation in humans.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.002 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".