Development of the gut microbiota in early life: The impact of cystic fibrosis and antibiotic treatment

Kristensen, Maartje; Prevaes, Sabine M. P. J.; Kalkman, Gino; Tramper-Stranders, Gerdien A; Hasrat, Raiza; Groot, Karin de Winter – de M.; Janssens, Hettie M.; Tiddens, Harm A.W.M.; Westreenen, Mireille van; Sanders, Elisabeth A. M.; Arets, B.; Keijser, Bart J. F.; Ent, Cornelis K. van der; Bogaert, Debby

doi:10.1016/j.jcf.2020.04.007

Cited by 49 publications

(95 citation statements)

References 46 publications

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“…Marinobacter is a genus of Proteobacteria found in sea water and a number of strains and species can degrade hydrocarbons [78]. Intracisternal type A particles are defective retroviruses in rodent genomes [79]. Bat gammaretrovirus are retroviruses that can cause malignancies and immune de ciencies in mammals, reptiles and birds [80].…”

Section: Discussionmentioning

confidence: 99%

Nisin Probiotic Prevents Periodontal Disease and Inflammation while Promoting Periodontal Regeneration and a Shift Toward a Healthy Microbiome/Virome

Kapila

L²,

Kuraji

et al. 2021

Preprint

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BackgroundDysbiosis of the oral microbiome mediates chronic periodontal disease, including its characteristic bone loss and host inflammatory response. Realignment of this microbial dysbiosis towards health may prevent disease. Treatment with antibiotics and probiotics can modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. Antibacterial peptides or bacteriocins, such as nisin, and nisin-producing probiotics, Lactococcus lactis, have not been examined in this context, yet warrant further examination because of their biomedical benefits in eradicating biofilms and oral pathogenic bacteria, and modulation of immune mechanisms. The goal of this study was to examine the potential for nisin and a nisin-producing probiotic to abrogate periodontal bone loss and related inflammatory landscape while modulating the composition of the oral microbiome. ResultsA polymicrobial mouse model of periodontal disease was employed for this purpose. In a disease context, nisin and the nisin-producing Lactococcus lactis probiotic significantly decreased the levels of periodontal pathogens, alveolar bone loss, oral inflammatory host response, and host-antibody response to these pathogens. Surprisingly, nisin and/or the nisin-producing L. lactis probiotic also enhanced the number of gingival fibroblasts, periodontal ligament cells, and bone lining cells in response to the polymicrobial infection. Nisin and probiotic treatment significantly shifted the oral bacteriome and virome towards the healthy control state. This shift was characterized by a unique signature; health was associated with a Proteobacteria (Marinobacter sp. B9-2), whereas 3 retroviruses (Golden Hamster Intracisternal A-particle H18, Bat gammaretrovirus, and Porcine type C oncovirus) were associated with disease. Specific disease-associated microbial species were highly correlated with IL-6 levels. ConclusionsNisin’s ability to shift the oral microbiome towards health, mitigate oral disease and the host immune response, and promote a novel regenerative periodontal phenotype, addresses key aspects of the pathogenesis of the disease. These benefits may negate the systemic effects associated with periodontal disease and reveal a new biomedical application for nisin in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Nisin Probiotic Prevents Periodontal Disease and Inflammation while Promoting Periodontal Regeneration and a Shift Toward a Healthy Microbiome/Virome

Kapila

L²,

Kuraji

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…As David Pride, Associate Director of Microbiology at UC San Diego, notes in an address to the 2019 North American Cystic Fibrosis Conference [ 17 ], “It is important to preserve our microbiomes because they play important roles in preventing pathogens from establishing infections, in the development of our immune systems to recognize and kill pathogens, and in metabolic processes such as the digestion of foods. Indiscriminate uses of antibiotics can have profound and long-lasting effects upon our microbiomes by killing many of the bacteria that make up our microbiome; thus, limiting their use may aid in keeping us healthy.” Prevalent, sometimes chronic, antibiotic use among CF patients results in a significant gut dysbiosis [ 18 ]. In addition, it has been noted that aggressive antibiotic use in CF, usually incident to the first manifestation of Staphylococcus aureus (SA), may allow Pseudomonas aeruginosa a greater foothold [ 19 ], and that aggressive treatment of Pseudomonas may, in turn, promote drug resistance and may allow additional bacteria, such as Stenotrophomonas maltophilia, an opportunity to proliferate [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Prevalent, sometimes chronic, antibiotic use among CF patients results in a significant gut dysbiosis [ 18 ]. In addition, it has been noted that aggressive antibiotic use in CF, usually incident to the first manifestation of Staphylococcus aureus (SA), may allow Pseudomonas aeruginosa a greater foothold [ 19 ], and that aggressive treatment of Pseudomonas may, in turn, promote drug resistance and may allow additional bacteria, such as Stenotrophomonas maltophilia, an opportunity to proliferate [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Case report: Three adult brothers with cystic fibrosis (delF508-delF508) maintain unusually preserved clinical profile in the absence of standard CF care

Bishop

2021

Respiratory Medicine Case Reports

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We present three cases in this report. Three adult brothers, homozygous for the delF508 cystic fibrosis mutation, have maintained an unusually preserved clinical condition even though they did not attend a CF Clinic during their childhood, do not attend a CF Clinic now, and do not follow standard CF care guidelines. The brothers use an alternative CF treatment regimen on which they have maintained normal lung function, height/weight, and bloodwork, and they utilize less than half the recommended dosage of pancreatic enzymes. The brothers culture only methicillin-sensitive Staphylococcus aureus, and have never cultured any other bacteria. Highly effective modulator therapies, such as elexacaftor/tezacaftor/ivacaftor, do not substantially reduce infection and inflammation in vivo in CF patients, and thus these three case reports are of special note in terms of suggesting adjunct therapeutic approaches. Finally, these three cases also raise important questions about standard CF care guidelines.

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“…Microbial dysbiosis at the site of the GI tract in CF patients has been described, with changes evident from birth through to adulthood [6][7][8]. Moreover, the extent of this divergence from healthy microbiota, initially due to loss of cystic fibrosis transmembrane conductance regulator (CFTR) function [9], is further compounded by routine treatment with broad spectrum antibiotics [10]. The reshaping of the gut microbiota may have functional consequences that could further impact on patients.…”

Section: Introductionmentioning

confidence: 99%

Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis

Marsh

Gavillet

Hanson

et al. 2021

Preprint

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Background: Most people with cystic fibrosis (pwCF) suffer from gastrointestinal symptoms and are at risk of gut complications. Gut microbiota dysbiosis is apparent within the CF population across all age groups, with evidence linking dysbiosis to intestinal inflammation and other markers of health. This pilot study aimed to investigate the potential relationships between the gut microbiota and gastrointestinal physiology, transit, and health. Study Design: Faecal samples from 10 pwCF and matched controls were subject to 16S rRNA sequencing. Results were combined with clinical metadata and MRI metrics of gut function to investigate relationships. Results: pwCF had significantly reduced microbiota diversity compared to controls. Microbiota compositions were significantly different, suggesting remodelling of core and rarer satellite taxa in CF. Dissimilarity between groups was driven by a variety of taxa, including Escherichia coli, Bacteroides spp., Clostridium spp., and Faecalibacterium prausnitzii. The core taxa were explained primarily by CF disease, whilst the satellite taxa were associated with pulmonary antibiotic usage, CF disease, and gut function metrics. Species-specific ordination biplots revealed relationships between taxa and the clinical or MRI-based variables observed. Conclusions: Alterations in gut function and transit resultant of CF disease are associated with the gut microbiota composition, notably the satellite taxa. Delayed transit in the small intestine might allow for the expansion of satellite taxa resulting in potential downstream consequences for core community function in the colon.

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Development of the gut microbiota in early life: The impact of cystic fibrosis and antibiotic treatment

Cited by 49 publications

References 46 publications

Nisin Probiotic Prevents Periodontal Disease and Inflammation while Promoting Periodontal Regeneration and a Shift Toward a Healthy Microbiome/Virome

Nisin Probiotic Prevents Periodontal Disease and Inflammation while Promoting Periodontal Regeneration and a Shift Toward a Healthy Microbiome/Virome

Case report: Three adult brothers with cystic fibrosis (delF508-delF508) maintain unusually preserved clinical profile in the absence of standard CF care

Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis

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