The aim of this review is to summarize the effect in host energy metabolism of the production of B group vitamins and short chain fatty acids (SCFA) by commensal, food-grade and probiotic bacteria, ...which are also actors of the mammalian nutrition. The mechanisms of how these microbial end products, produced by these bacterial strains, act on energy metabolism will be discussed. We will show that these vitamins and SCFA producing bacteria could be used as tools to recover energy intakes by either optimizing ATP production from foods or by the fermentation of certain fibers in the gastrointestinal tract (GIT). Original data are also presented in this work where SCFA (acetate, butyrate and propionate) and B group vitamins (riboflavin, folate and thiamine) production was determined for selected probiotic bacteria.
The gut microbiota plays a major role in intestinal health, and an imbalance in its composition can lead to chronic gut inflammation and a predisposition to developing colorectal cancer (CRC). ...Currently, the use of probiotic bacteria represents an emerging alternative to treat and prevent cancer. Moreover, consumption of these beneficial bacteria may also favorably modulate the composition of the gut microbiota, which has been described in several studies to play an important role in CRC carcinogenesis. In this context, the aim of this study was to assess the protective effect of oral treatment with
BL23, a probiotic strain well known for its anti-inflammatory and anticancer properties. First, CRC was induced in C57BL6 mice by a single intraperitoneal injection with azoxymethane (8 mg/kg), followed by four courses of dextran sodium sulfate (2.5%) in drinking water that were separated by an adjustable recovery period. At the time of sacrifice (day 46), tumor incidence, histological scores, and epithelial proliferation were determined in colon samples. Our results show that
BL23 significantly protected mice against CRC development; specifically,
BL23 treatment reduced histological scores and proliferative index values. In addition, our analysis revealed that
BL23 had an immunomodulatory effect, mediated through the downregulation of the IL-22 cytokine, and an antiproliferative effect, mediated through the upregulation of
, and
. Finally,
BL23 treatment tended to counterbalance CRC-induced dysbiosis in mice, as demonstrated by an analysis of fecal microbiota. Altogether our results demonstrate the high potential of
BL23 for the development of new, probiotic-based strategies to fight CRC.
is a major member of the Firmicutes phylum and one of the most abundant bacteria in the healthy human microbiota.
depletion has been reported in several intestinal disorders, and more consistently in ...Crohn's disease (CD) patients. Despite its importance in human health, only few microbiological studies have been performed to isolate novel
strains in order to better understand the biodiversity and physiological diversity of this beneficial commensal species. In this study, we described a protocol to isolate novel
strains from feces of healthy volunteers as well as a deep molecular and metabolic characterization of these isolated strains. These
strains were classified in two phylogroups and three clusters according to 16S rRNA sequences and results support that they would belong to two different genomospecies or genomovars as no genome sequencing has been performed in this work. Differences in enzymes production, antibiotic resistance and immunomodulatory properties were found to be strain-dependent. So far, all
isolates share some characteristic such as (i) the lack of epithelial cells adhesion, plasmids, anti-microbial, and hemolytic activity and (ii) the presence of DNAse activity. Furthermore, Short Chain Fatty Acids (SCFA) production was assessed for the novel isolates as these products influence intestinal homeostasis. Indeed, the butyrate production has been correlated to the capacity to induce IL-10, an anti-inflammatory cytokine, in peripheral blood mononuclear cells (PBMC) but not to the ability to block IL-8 secretion in TNF-α-stimulated HT-29 cells, reinforcing the hypothesis of a complex anti-inflammatory pathway driven by
. Altogether, our results suggest that some
strains could represent good candidates as next-generation probiotic.
Food-grade Lactic Acid Bacteria (LAB) have been safely consumed for centuries by humans in fermented foods. Thus, they are good candidates to develop novel oral vectors, constituting attractive ...alternatives to attenuated pathogens, for mucosal delivery strategies. Herein, this review summarizes our research, up until now, on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of our work has been based on the model LAB Lactococcus lactis, for which we have developed efficient genetic tools, including expression signals and host strains, for the heterologous expression of therapeutic proteins such as antigens, cytokines and enzymes. Resulting recombinant lactococci strains have been tested successfully for their prophylactic and therapeutic effects in different animal models: i) against human papillomavirus type 16 (HPV-16)-induced tumors in mice, ii) to partially prevent a bovine β-lactoglobulin (BLG)-allergic reaction in mice and iii) to regulate body weight and food consumption in obese mice. Strikingly, all of these tools have been successfully transposed to the Lactobacillus genus, in recent years, within our laboratory. Notably, anti-oxidative Lactobacillus casei strains were constructed and tested in two chemically-induced colitis models. In parallel, we also developed a strategy based on the use of L. lactis to deliver DNA at the mucosal level, and were able to show that L. lactis is able to modulate the host response through DNA delivery. Today, we consider that all of our consistent data, together with those obtained by other groups, demonstrate and reinforce the interest of using LAB, particularly lactococci and lactobacilli strains, to develop novel therapeutic protein mucosal delivery vectors which should be tested now in human clinical trials.
The human gut is one of the most complex ecosystems, composed of 1013-1014 microorganisms which play an important role in human health. In addition, some food products contain live bacteria which ...transit through our gastrointestinal tract and could exert beneficial effects on our health (known as probiotic effect). Among the numerous proposed health benefits attributed to commensal and probiotic bacteria, their capacity to interact with the host immune system is now well demonstrated. Currently, the use of recombinant lactic acid bacteria to deliver compounds of health interest is gaining importance as an extension of the probiotic concept. This review summarizes some of the recent findings and perspectives in the study of the crosstalk of both commensal and probiotic bacteria with the human host as well as the latest studies in recombinant commensal and probiotic bacteria. Our aim is to highlight the potential roles of recombinant bacteria in this ecosystem.
represents approximately 5% of the total fecal microbiota in healthy adults being one of the most abundant bacterium in the human intestinal microbiota of healthy adults. Furthermore, this bacterium ...has been proposed to be a sensor and a major actor of the human intestinal health because of its importance in the gut ecosystem. In this context,
population levels have been found to be reduced in patients suffering from several syndromes and diseases such as inflammatory bowel diseases. These diseases are characterized by a breakage of the intestinal homeostasis called dysbiosis and the use of
as a next generation probiotic (also called live biotherapeutics) has been proposed as a natural tool to restore such dysbiosis within the gut. Nevertheless, despite the potential importance of this bacterium in human health, little is known about its main effectors underlying its beneficial effects. In this perspective note, we aim to present the actual state in the research about
effectors and the future milestones in this field.
The mammalian target of rapamycin (mTOR) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B or Akt (PKB/Akt) signaling pathways are considered as two but somewhat interconnected ...significant immune pathways which play complex roles in a variety of physiological processes as well as pathological conditions. Aberrant activation of PI3K/Akt/mTOR signaling pathways has been reported to be associated in a wide variety of human diseases. Over the past few years, growing evidence in in vitro and in vivo models suggest that this sophisticated and subtle cascade mediates the orchestration of the immune response in health and disease through exposure to probiotics. An expanding body of literature has highlighted the contribution of probiotics and PI3K/Akt/mTOR signaling pathways in gastrointestinal disorders, metabolic syndrome, skin diseases, allergy, salmonella infection, and aging. However, longitudinal human studies are possibly required to verify more conclusively whether the investigational tools used to understand the regulation of these pathways might provide effective approaches in the prevention and treatment of various disorders. In this Review, we summarize the experimental evidence from recent peer-reviewed studies and provide a brief overview of the causal relationship between the effects of probiotics and their metabolites on the components of PI3K/Akt/mTOR signaling pathways and human disease.
Most cervical cancer (CxCa) are related to persistent infection with high-risk human papillomavirus (HR-HPV) in the cervical mucosa, suggesting that an induction of mucosal cell-mediated immunity ...against HR-HPV oncoproteins can be a promising strategy to fight HPV-associated CxCa. From this perspective, many pre-clinical and clinical trials have proved the potential of lactic acid bacteria (LAB) genetically modified to deliver recombinant antigens to induce mucosal, humoral and cellular immunity in the host. Altogether, the outcomes of these studies suggest that there are several key factors to consider that may offer guidance on improvement protein yield and improving immune response. Overall, these findings showed that oral LAB-based mucosal HPV vaccines expressing inducible surface-anchored antigens display a higher potential to induce particularly specific systemic and mucosal cytotoxic cellular immune responses. In this review, we describe all LAB-based HPV vaccine investigations by reviewing databases from international studies between 2000 and 2020. Our aim is to promote the therapeutic HPV vaccines knowledge and to complete the gaps in this field to empower scientists worldwide to make proper decisions regarding the best strategies for the development of therapeutic HPV vaccines.
A fat‐enriched diet modifies intestinal microbiota and initiates a low‐grade inflammation, insulin resistance and type‐2 diabetes. Here, we demonstrate that before the onset of diabetes, after only ...one week of a high‐fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob/ob mouse. This ‘metabolic bacteremia’ is characterized by an increased co‐localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non‐pathogenic Escherichia coli. The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals' overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD‐induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets.
Abstract
In humans, many diseases are associated with alterations in gut microbiota, namely increases or decreases in the abundance of specific bacterial groups. One example is the genus ...Faecalibacterium. Numerous studies have underscored that low levels of Faecalibacterium are correlated with inflammatory conditions, with inflammatory bowel disease (IBD) in the forefront. Its representation is also diminished in the case of several diseases, including colorectal cancer (CRC), dermatitis, and depression. Additionally, the relative presence of this genus is considered to reflect, at least in part, intestinal health status because Faecalibacterium is frequently present at reduced levels in individuals with gastrointestinal diseases or disorders. In this review, we first thoroughly describe updates to the taxonomy of Faecalibacterium, which has transformed a single-species taxon to a multispecies taxon over the last decade. We then explore the links discovered between Faecalibacterium abundance and various diseases since the first IBD-focused studies were published. Next, we examine current available strategies for modulating Faecalibacterium levels in the gut. Finally, we summarize the mechanisms underlying the beneficial effects that have been attributed to this genus. Together, epidemiological and experimental data strongly support the use of Faecalibacterium as a next-generation probiotic (NGP) or live biotherapeutic product (LBP).
The authors describe (i) updates to the taxonomy of Faecalibacterium, which has transformed a single-species taxon to a multispecies taxon over the last decade, (ii) the links that have been discovered between Faecalibacterium abundance and various diseases since the first IBD-focused studies were published, and (iii) current available strategies for modulating Faecalibacterium levels in the gut.
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