Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth

Zagato, Elena; Pozzi, Chiara; Bertocchi, Alice; Schioppa, Tiziana; Saccheri, Fabiana; Guglietta, Silvia; Fosso, Bruno; Melocchi, Laura; Nizzoli, Giulia; Troisi, Jacopo; Marzano, Marinella; Oresta, Bianca; Spadoni, Ilaria; Atarashi, Koji; Carloni, Sara; Arioli, Stefania; Fornasa, Giulia; Asnicar, Francesco; Segata, Nicola; Guglielmetti, Simone; Honda, Kenya; Pesole, Graziano; Vermi, William; Penna, Giuseppe; Rescigno, María

doi:10.1038/s41564-019-0649-5

Cited by 268 publications

(164 citation statements)

References 63 publications

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“…[ 2,3 ] Therefore, regulating gut microbiota has been viewed as a promising route for treating digestive diseases, especially colon cancers. [ 4–7 ] Previously, phage‐based intervention of gut microbiota and genetically engineered bacteria showed initial therapeutic effects in animal models of colon cancers. [ 8,9 ] Most importantly, fecal microbiota transplant (FMT) that transfers stool from a healthy human donor to another human recipient was also proved to be effective in the clinical treatment of cancer.…”

Section: Figurementioning

confidence: 99%

Prebiotics‐Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer

Zheng

et al. 2020

Advanced Materials

140

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While microbial‐based therapy has been considered as an effective strategy for treating diseases such as colon cancer, its safety remains the biggest challenge. Here, probiotics and prebiotics, which possess ideal biocompatibility and are extensively used as additives in food and pharmaceutical products, are combined to construct a safe microbiota‐modulating material. Through the host–guest chemistry between commercial Clostridium butyricum and chemically modified prebiotic dextran, prebiotics‐encapsulated probiotic spores (spores‐dex) are prepared. It is found that spores‐dex can specifically enrich in colon cancers after oral administration. In the lesion, dextran is fermented by C. butyricum, and thereby produces anti‐cancer short‐chain fatty acids (SCFAs). Additionally, spores‐dex regulate the gut microbiota, augment the abundance of SCFA‐producing bacteria (e.g., Eubacterium and Roseburia), and markedly increase the overall richness of microbiota. In subcutaneous and orthotopic tumor models, drug‐loaded spores‐dex inhibit tumor growth up to 89% and 65%, respectively. Importantly, no obvious adverse effect is found. The work sheds light on the possibility of using a highly safe strategy to regulate gut microbiota, and provides a promising avenue for treating various gastrointestinal diseases.

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Section: Figurementioning

confidence: 99%

Prebiotics‐Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer

Zheng

et al. 2020

Advanced Materials

140

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“…Importantly, these bacteria were positively or negatively correlated with cytokines secreted by mesenteric lymphocytes. For example, Faecalibaculum has been shown to have anti-tumor properties ( 47 ) and Candidatus_Saccharimonas is involved in maintaining normal intestinal function ( 48 ). Rikenella is positively correlated with inflammatory factors ( 49 ) and correlated with chronic systemic inflammatory disorders ( 50 ), suggesting that the Rikenella contributes to promoting inflammation.…”

Section: Discussionmentioning

confidence: 99%

Mushroom Bulgaria inquinans Modulates Host Immunological Response and Gut Microbiota in Mice

Sang

Xie

et al. 2020

Front. Nutr.

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We aimed to determine the prebiotic impact of Mushroom Bulgaria inquinans (BI) on the host immune response and gut microbiota. Male C57BL/6 mice were fed a diet supplemented with 0, 1, or 2% BI for 4 wks. Compared to mice fed with a control diet (0% BI), mice fed with 1 or 2% BI had an increase of T cell proliferation from the spleen, but such change was not found between 1 and 2% BI treated mice. Also, BI at 2% increased the production of IL-2 of splenocytes stimulated with T-cell mitogens, but BI at 1 and 2% did not affect productions of other splenic-T cell cytokines including IL-4, IL-10, and IFN-γ. Interestingly, BI at 1 or 2% inhibited T cell proliferation of mesenteric lymph node (mLN) but this effect was not found between 1 and 2% BI treated mice. Furthermore, BI inhibited the production of IL-2 in anti-CD3/CD28-stimulated T cells from mLN in a dose-dependent manner. Meanwhile, BI at 2%, not 1% inhibited the production of IL-4, IL-10, and IFN-γ of mLN. Since BI at 2% produced a more significant effect on the immune response, we further used BI at 2% to evaluate the effect of BI on gut microbiota. Of note, BI reduced the diversity of gut microbiota and resulted in an increase of Faecalibaculum and Parabacteroides abundance and the decrease of Allobaculum, Candidatus _ Saccharimonas , and Rikenella abundance at the genus level. Finally, the correlation was observed between specific bacteria genera and the productions of T-cell cytokines from mesenteric lymphocytes: Rikenella and Candidatus_Saccharimonas correlated positively with IL-2, IL-4, IL-10, and IFN-γ; Bacteroides and Parabacteroides correlated negatively with IL-2 and IL-4; Faecalibaculum correlated negatively with IFN-γ and IL-4 and Bacteroides and Bifidobacterium correlated negatively with IFN-γ. The specific role of each intestinal microbiota observed is still unclear, but BI might exert a prebiotic effect on gut microbiota by increasing the abundance of potentially beneficial bacteria ( Faecalibaculum ). This is helpful for further demonstrating the healthy-promotion mechanism of B. inquinans .

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“…We further demonstrated that Faecalibaculum, and Bi dobacterium also correlated positively with SCFAs production, antioxidant enzymes, correlated negatively with in ammatory cytokines. Supported by a recent study, Faecalibaculum rodentium is strongly suppressed during intestinal tumorigenesis and produces protective SCFAs to inhibit tumor cell proliferation [56]. Similarly, Bi dobacterium is another SCFAs-producing bacterium with profound immune modulatory effects [57].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Bi dobacterium is another SCFAs-producing bacterium with profound immune modulatory effects [57]. It is worth mentioning that, although Akkermansia is likely a major microbe that mediates much of the EGCG bene ts, several other SCFAs-producing bacteria such as Faecalibaculum and Bi dobacterium [56,57] enriched in response to prophylactic EGCG are also of concern.…”

Section: Discussionmentioning

confidence: 99%

Oral, but not rectal delivery of epigallocatechin-3-gallate alleviates colitis by regulating the gut microbiota, oxidative stress, inflammation, and barrier integrity

Huang

et al. 2020

Preprint

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Background: Alteration of the gut microbiota may contribute to the development of inflammatory bowel diseases (IBDs). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBDs alleviation. However, it is unclear whether EGCG attenuates IBDs through direct improvement of gastrointestinal function or indirect alteration of the structure and function of the gut microbiota.Results: We first investigated the therapeutic effects of EGCG on disease severity, oxidative stress, inflammation, barrier function, and gut microbiota in murine colitis model, and further demonstrate it via EGCG pre-supplementation. We revealed that, oral, but not rectal, delivery of EGCG alleviated the severity of colitis through attenuation of anti-oxidative and anti-inflammatory response. Mucin-secreting goblet cell number, barrier function gene expression levels, and the integrity of tight junctions in the colon were also enhanced by oral EGCG. Additionally, we observed distinct EGCG-mediated alternation in the gut microbiome, as highlighted by increased Akkermansia abundance and butyrate production. Furthermore, we revealed that prophylactic oral application of EGCG for 21 days prior to the onset of dextran sodium sulfate (DSS)-induced colitis also ameliorated colonic damage, oxidative stress, and inflammatory response. Prophylactic EGCG significantly enriched Akkermansia, Faecalibaculum, and Bifidobacterium and enhanced acetate, propionate and butyrate production in DSS-treated mice. Moreover, scores of differential microbes, in particular Akkermansia, showed a strong positive correlation with short-chain fatty acids (SCFAs) and antioxidant enzyme levels in both the plasma and colon, but a negative association with inflammatory cytokines and malondialdehyde.Conclusions: EGCG is capable of treating DSS-induced colitis both therapeutically and prophylactically by inducing a pronounced anti-oxidative and anti-inflammatory response. Attenuation of colitis by oral, but not rectal administration of, EGCG suggests an intimate involvement of the gut microbiota. Increased Akkermansia and subsequent protective SCFAs production may be largely responsible for the anti-inflammatory and anti-oxidative function of EGCG, leading to restoration of intestinal epithelial homeostasis of the host. These findings provide novel insights into EGCG-mediated remission of IBDs and the rationale for devising more effective therapeutic strategies for IBDs.

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Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth

Cited by 268 publications

References 63 publications

Prebiotics‐Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer

Prebiotics‐Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer

Mushroom Bulgaria inquinans Modulates Host Immunological Response and Gut Microbiota in Mice

Oral, but not rectal delivery of epigallocatechin-3-gallate alleviates colitis by regulating the gut microbiota, oxidative stress, inflammation, and barrier integrity

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