Galactose metabolism and health

Coelho, Ana Daniela; Berry, Gerard T.; Rubio-Gozalbo, M. Estela

doi:10.1097/mco.0000000000000189

Cited by 183 publications

(136 citation statements)

References 33 publications

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“…However, the distinct transcription patterns between in vitro and in vivo , as well as between those after 14 days and 28 days of probiotic uptake, strongly suggest that the detected probiotic transcriptomes reflect those have survived the GI tracts. Our results support the previous hypothesis of the cell lysis for the dead ingested bacteria (20, 42). We do not exclude the possibility that the dead probiotic bacteria might still yield fragmented DNA signals.…”

Section: Discussionsupporting

confidence: 93%

“…At day-28, the late stage of ingestion, expression of a cluster of genes (226) was specifically increased (M3 module). These genes were involved in the biosynthesis and/or metabolism of the well-known probiotic molecular including galactose (20), carbohydrate utilization (33) and metabolism of propanoate the key member of SCFA (34) (Figure 6d). We found L. casei genes for ascorbate and aldarate metabolism were globally upregulated, suggesting a novel class of probiotic molecule.…”

Section: Resultsmentioning

confidence: 99%

“…Probiotic microorganisms are generally part of our transient microbiome, which commonly include bacterial strains in the genus Lactobacillus , Bifidobacterium , Enterococcus , and yeasts such as S. boulardii (14, 15). After it was coined in 1965, probiotic bacteria have been extensively studied for its wide utilization in dairy foods (16) and prophylaxis and control of a number of disease (17-19), which are primarily focused on their fate, activity and impact on the human gut microbiota (14, 20, 21). Probiotics have been reported to benefit human health in different ways.…”

Section: Introductionmentioning

confidence: 99%

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Metatranscriptome profiling of the dynamic transcription of mRNA and sRNA of a probioticLactobacillusstrain in human gut

Wang

Sun

Qiao

et al. 2018

Preprint

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20Metatranscriptomic sequencing has recently been applied to study how pathogens and probiotics 21 affect human gastrointestinal (GI) tract microbiota, which provides new insights into their 22 mechanisms of action. In this study, metatranscriptomic sequencing was applied to deduce the in 23 vivo expression patterns of an ingested Lactobacillus casei strain, which was compared with its in 24 vitro growth transcriptomes. Extraction of the strain-specific reads revealed that transcripts from 25 the ingested L. casei were increased, while those from the resident L. paracasei strains remained 26unchanged. Mapping of all metatranscriptomic reads and transcriptomic reads to L. casei genome 27 showed that gene expression in vitro and in vivo differed dramatically. About 39% (1163) mRNAs 28 and 45% (93) sRNAs of L. casei well-expressed were repressed after ingested into human gut. 29Expression of ABC transporter genes and amino acid metabolism genes was induced at day-14 of 30 ingestion; and genes for sugar and SCFA metabolisms were activated at day-28 of ingestion. 31Moreover, expression of sRNAs specific to the in vitro log phase was more likely to be activated 32 in human gut. Expression of rli28c sRNA with peaked expression during the in vitro stationary 33 phase was also activated in human gut; this sRNA repressed L. casei growth and lactic acid 34 production in vitro. These findings implicate that the ingested L. casei might have to successfully 35 change its transcription patterns to survive in human gut, and the time-dependent activation 36 patterns indicate a highly dynamic cross-talk between the probiotic and human gut including its 37 microbe community. 38 39 Keywords: Metagenomic, metatranscriptomic, probiotic, Lactobacillus, transcriptional regulation, 40 gut microbiota 41 42 Dynamic transcription of probiotic mRNAs and sRNAs in human gut 3 Importance 43 Probiotic bacteria are important in food industry and as model microorganisms in understanding 44 bacterial gene regulation. Although probiotic functions and mechanisms in human gastrointestinal 45 tract are linked to the unique probiotic gene expression, it remains elusive how transcription of 46probiotic bacteria is dynamically regulated after being ingested. Previous study of probiotic gene 47 expression in human fecal samples has been restricted due to its low abundance and the presence 48 of of closely related species. In this study, we took the advantage of the good depth of 49 metatranscriptomic sequencing reads and developed a strain-specific read analysis method to 50 discriminate the transcription of the probiotic Lactobacillus casei and those of its resident relatives. 51This approach and additional bioinformatics analysis allowed the first study of the dynamic 52 transcriptome profiles of probiotic L casei in vivo. The novel findings indicate a highly regulated 53 repression and dynamic activation of probiotic genome in human GI tract. 54 55 56

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metatranscriptome profiling of the dynamic transcription of mRNA and sRNA of a probioticLactobacillusstrain in human gut

Wang

Sun

Qiao

et al. 2018

Preprint

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“…A negative result does not exclude the disease, and full gene sequencing, including deep intronic regions, may be required (Coelho et al 2015b; Wadelius et al 1993). …”

Section: Diagnosismentioning

confidence: 99%

“…Functional characterization of c.820 + 13A>G revealed it activates the cryptic donor site c.820 + 14_820 + 15, leading to the exonization of the first 13 nucleotides of intron 8, thereby confirming that this intronic variation is actually a disease-causing mutation. Coelho and coworkers employed two locked nucleic acid (LNA) oligonucleotides and the mini-gene approach to successfully restore the splicing profile, thus establishing a proof of concept for the application of antisense therapy for mis-splicing mutations in classic galactosemia (Coelho et al 2015b). …”

Section: Therapeutic Approaches In Classic Galactosemiamentioning

confidence: 99%

Sweet and sour: an update on classic galactosemia

Coelho

Rubio-Gozalbo

Vicente

et al. 2017

J of Inher Metab Disea

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Classic galactosemia is a rare inherited disorder of galactose metabolism caused by deficient activity of galactose-1-phosphate uridylyltransferase (GALT), the second enzyme of the Leloir pathway. It presents in the newborn period as a life-threatening disease, whose clinical picture can be resolved by a galactose-restricted diet. The dietary treatment proves, however, insufficient in preventing severe long-term complications, such as cognitive, social and reproductive impairments. Classic galactosemia represents a heavy burden on patients’ and their families’ lives. After its first description in 1908 and despite intense research in the past century, the exact pathogenic mechanisms underlying galactosemia are still not fully understood. Recently, new important insights on molecular and cellular aspects of galactosemia have been gained, and should open new avenues for the development of novel therapeutic strategies. Moreover, an international galactosemia network has been established, which shall act as a platform for expertise and research in galactosemia. Herein are reviewed some of the latest developments in clinical practice and research findings on classic galactosemia, an enigmatic disorder with many unanswered questions warranting dedicated research.

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