Paraprobiotic Lacticaseibacillus rhamnosus Protects Intestinal Damage in an Experimental Murine Model of Mucositis

Trindade, Luísa Martins; Torres, Lícia; Matos, Isabel David; Miranda, Vivian C.; Jesus, Luís Cláudio Lima de; Cavalcante, Gregório Grama; Oliveira, Jonathan Júnio de Souza; Cassali, Geovanni Dantas; Mancha-Agresti, Pamela; Azevedo, Vasco; Maioli, Tatiani Uceli; Cardoso, Valbert Nascimento; Martins, Fernanda Pereira; Generoso, Simone de Vasconcelos

doi:10.1007/s12602-021-09842-z

Cited by 22 publications

(20 citation statements)

References 57 publications

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“…These data are similar to the findings of Prisciandaro et al [33], demonstrating that Escherichia coli Nissle 1917 and Limosilactobacillus fermentum BR11 supernatant did not improve weight loss in mice with intestinal mucositis [33]. On the other hand, the consumption of heat-killed L. delbrueckii CIDCA 133 ameliorated the weight loss in BALB/c mice after 5-FU administration, similarly to viable bacteria, as previously reported by De Jesus et al [29], and also corroborating with Trindade et al [43], who reported that heat-killed Lacticaseibacillus rhamnosus CGMCC1.3724 strain influenced weight recovery of 5-FU inflamed mice.…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, secreted factors of E. coli Nissle 1917 attenuated the epithelial barrier disruption induced by enteropathogenic E. coli in Caco-2 cells by enhancing the gene expression of tight junction proteins zonulin-1, claudin-14, and claudin-2 [ 65 ]. Trindade et al [ 43 ] also reported that paraprobiotics L. rhamnosus CGMCC1.3724 reduced intestinal permeability induced by 5-FU and enhanced Muc2 gene expression. Promising results were also reported with inactivated B. longum K2-21-4, which modulated the gene expression of claudin-1, zonulin-1, and occludin disrupted by lipopolysaccharide (LPS) in colon epithelial cells [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

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Paraprobiotics and Postbiotics of Lactobacillus delbrueckii CIDCA 133 Mitigate 5-FU-Induced Intestinal Inflammation

et al. 2022

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Intestinal mucositis is a commonly reported side effect in oncology practice. Probiotics are considered an excellent alternative therapeutic approach to this debilitating condition; however, there are safety questions regarding the viable consumption of probiotics in clinical practice due to the risks of systemic infections, especially in immune-compromised patients. The use of heat-killed or cell-free supernatants derived from probiotic strains has been evaluated to minimize these adverse effects. Thus, this work evaluated the anti-inflammatory properties of paraprobiotics (heat-killed) and postbiotics (cell-free supernatant) of the probiotic Lactobacillus delbrueckii CIDCA 133 strain in a mouse model of 5-Fluorouracil drug-induced mucositis. Administration of paraprobiotics and postbiotics reduced the neutrophil cells infiltrating into the small intestinal mucosa and ameliorated the intestinal epithelium architecture damaged by 5-FU. These ameliorative effects were associated with a downregulation of inflammatory markers (Tlr2, Nfkb1, Il12, Il17a, Il1b, Tnf), and upregulation of immunoregulatory Il10 cytokine and the epithelial barrier markers Ocln, Cldn1, 2, 5, Hp and Muc2. Thus, heat-killed L. delbrueckii CIDCA 133 and supernatants derived from this strain were shown to be effective in reducing 5-FU-induced inflammatory damage, demonstrating them to be an alternative approach to the problems arising from the use of live beneficial microorganisms in clinical practice.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Paraprobiotics and Postbiotics of Lactobacillus delbrueckii CIDCA 133 Mitigate 5-FU-Induced Intestinal Inflammation

et al. 2022

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“…These findings are consistent with other studies that also observed beneficial effects of different probiotic microorganisms in decreasing inflammatory cell infiltrate induced by 5-FU administration, such as Bifidobacterium sp . ( Kato et al, 2017 ; Quaresma et al, 2020 ), Lactobacillus acidophilus ( Oh et al, 2018 ) Lacticaseibacillus rhamnosus ( Trindade et al, 2021 ) and Rhodotorula mucilaginosa ( Coutinho et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown the efficacy of various LABs in preventing intestinal mucositis by regulating the microbiota in dysbiosis ( Chang et al, 2018 ), improving the inflammatory process, modulating oxidative stress ( Justino et al, 2015 ; Hu et al, 2020 ; Quaresma et al, 2020 ), and protecting the epithelial barrier by maintaining the integrity of tight junction proteins and goblet cells ( Yeung et al, 2015 ; Barroso et al, 2021 ). Despite these beneficial effects, the use of these inactivated microorganisms has also been highlighted ( Jin et al, 2020 ; Nakai et al, 2021 ; Trindade et al, 2021 ), to minimize possible risks of bacteria translocation producing systemic infections, especially in premature infants or immune-compromised patients ( Doron and Snydman, 2015 ; Zawistowska-Rojek and Tyski, 2018 ). In addition, it has been demonstrated that many of the effects (such as immunomodulation and microbiota regulation) of inactivated probiotics are similar to their metabolically active form, suggesting that these effects can be attributed to cell wall proteins of these microorganisms that interact with host cells during their passage through the gastrointestinal tract (GIT) ( Hsieh et al, 2016 ; Aiba et al, 2017 ; Jin et al, 2020 ; Nobre et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway

et al. 2022

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Intestinal mucositis promoted by the use of anticancer drugs is characterized by ulcerative inflammation of the intestinal mucosa, a debilitating side effect in cancer patients undergoing treatment. Probiotics are a potential therapeutic option to alleviate intestinal mucositis due to their effects on epithelial barrier integrity and anti-inflammatory modulation. This study investigated the health-promoting impact of Lactobacillus delbrueckii CIDCA 133 in modulating inflammatory and epithelial barrier markers to protect the intestinal mucosa from 5-fluorouracil-induced epithelial damage. L. delbrueckii CIDCA 133 consumption ameliorated small intestine shortening, inflammatory cell infiltration, intestinal permeability, villus atrophy, and goblet cell count, improving the intestinal mucosa architecture and its function in treated mice. Upregulation of Muc2, Cldn1, Hp, F11r, and Il10, and downregulation of markers involved in NF-κB signaling pathway activation (Tlr2, Tlr4, Nfkb1, Il6, and Il1b) were observed at the mRNA level. This work suggests a beneficial role of L. delbrueckii strain CIDCA 133 on intestinal damage induced by 5-FU chemotherapy through modulation of inflammatory pathways and improvement of epithelial barrier function.

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“…Tightening the intestinal mucosal barrier also plays an important role in suppressing systemic inflammation and consequent neuroinflammation. Numerous results suggest that the gut microbiome modulate the intestinal barrier function [149][150][151]. In this context, butyrate has been shown to enhance the intestinal barrier function through maintenance of the expression of tight junction proteins including claudins, occludin, and zonula occludens protein-1 (ZO-1) [152], and an animal study has demonstrated that oral administration of C. butyricum or butyrate reduces intestinal injury associated with severe acute pancreatitis [153].…”

Section: Anti-inflammatory Effectmentioning

confidence: 99%

How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

Suda

Matsuda

2022

IJMS

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Accumulating evidence suggests that the gut microbiome influences the brain functions and psychological state of its host via the gut–brain axis, and gut dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown that a depletion of the gut microbiota leads to behavioral changes, and is associated with pathological changes, including abnormal stress response and impaired adult neurogenesis. Short-chain fatty acids such as butyrate are known to contribute to the up-regulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis causes decreased levels of BDNF, which could affect neuronal development and synaptic plasticity. Increased gut permeability causes an influx of gut microbial components such as lipopolysaccharides, and the resultant systemic inflammation may lead to neuroinflammation in the central nervous system. In light of the fact that gut microbial factors contribute to the initiation and exacerbation of depressive symptoms, this review summarizes the current understanding of the molecular mechanisms involved in MDD onset, and discusses the therapeutic potential of probiotics, including butyrate-producing bacteria, which can mediate the microbiota–gut–brain axis.

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Paraprobiotic Lacticaseibacillus rhamnosus Protects Intestinal Damage in an Experimental Murine Model of Mucositis

Cited by 22 publications

References 57 publications

Paraprobiotics and Postbiotics of Lactobacillus delbrueckii CIDCA 133 Mitigate 5-FU-Induced Intestinal Inflammation

Paraprobiotics and Postbiotics of Lactobacillus delbrueckii CIDCA 133 Mitigate 5-FU-Induced Intestinal Inflammation

Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway

How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

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