Biology subjects

Bellanger, A.

Publications and source records attributed to Bellanger, A..

4 recordsLinked to original sources

bioRxiv2025

Human milk bacteria assembled into functionally distinct synthetic communities in infant formula differently affect intestinal physiology and microbiota in neonatal mini-piglets

The contribution of Human milk (HM) microbiota to infant gut health was addressed by evaluating the impact of HM bacteria, combined in two synthetic communities (SynComs) exhibiting anti-inflammatory (AI) or high immunomodulatory (HI) properties in vitro, on gut immune and barrier functions, and microbiota. Neonatal mini-piglets were fed either a formula without supplementation (CTRL) or supplemented with AI or HI SynComs, and were compared to sow milk-fed (SM) piglets over a period of 24 days. Feces were collected on postnatal day (PND) 8, and ileal, colonic and fecal samples were collected on PND24. The multifactorial analysis indicated that the two HM-derived SynComs impacted microbiota and intestinal functions differently. Several genera, mainly belonging to Bacillota, displayed different relative abundances between the formula-fed groups at both PND8 and PND24. At PND8, the fecal sIgA level in HI piglets was slightly lower than in SM piglets but markedly higher than in CTRL and AI piglets. SynComs HI and/or AI slightly increased the expression of genes involved in pro-inflammatory (IL6, TNFaR1), antioxidant (SOD2), anti-inflammatory (SOCS3) and Treg (FOXP3) pathways in ileal and colonic tissues compared with the CTRL group. Systemic immune functions were also modulated with a cytokine secretion capacity of peripheral blood mononuclear cells that tended to be higher with HI supplementation. Interestingly, SynCom bacteria were correlated with several ileal and colonic genera, and both were correlated with physiological variables. Overall, our findings support the influence of HM bacteria, provided in formulas as SynCom at a physiological concentration, on gut microbiota and functions. ImportanceEarly-life environmental factors, such as neonatal diet, influence the gut microbiota, which plays a key role in the functional development of the gut. However, the role of the human milk (HM) microbiota, particularly with regard to the immunomodulatory properties of HM bacteria, is not well understood. This study investigates the differential effects of two synthetic communities with a similar taxonomic composition representative of the taxonomic diversity of the HM microbiota. Thse communities exhibit contrasting immunomodulatory properties that were previously characterized using an in vitro intestinal quadricellular model. Daily supplementation with these two SynComs modulated the composition of the gut microbiota and the gut physiology differently, particularly the intestinal immune signatures. In conclusion, the functional profile of bacteria within the HM microbiota may induce distinct developmental profiles of gut physiology in infants.

physiology↗

bioRxiv2024

New insights into the cultivability of human milk microbiota from ingestion to digestion and implications for its immunomodulatory properties

Human milk (HM) microbiota is increasingly studied for its potential health benefits. However, the physiological state of HM bacteria and consequently their effects on gut homeostasis remain a question. This study investigated the physiological state of the HM microbiota by characterizing its cultivable fraction, as it might be at the point of ingestion and assessing the effects of digestion on the cultivability and immunomodulatory properties of six prevalent HM strains. The microbiota of 28 HM samples was analysed by 16S metabarcoding either directly on raw milk (raw milk microbiota, RM) or on the complete cultivable fraction obtained from seven non-selective media (cultivable milk microbiota, CM). Diversity was lower in CM than in RM, with 32 versus 435 genera and a median of 7 versus 69 genera per sample in CM and RM, respectively. CM also showed under-representation of strictly anaerobic genera. Factors like parity and iron or vitamin supplementation affected RM and/or CM. In vitro gastrointestinal digestion moderately impacted strain cultivability. However, most strains partially or completely lost their immunomodulatory properties on the monocyte THP1 cell line after digestion, except a Staphylococcus epidermidis strain that gained immunomodulatory potential.

microbiology↗

bioRxiv2023

Multi-level 3D genome organization deteriorates during breast cancer progression

Breast cancer entails intricate alterations in genome organization and expression. However, how three-dimensional (3D) chromatin structure changes in the progression from a normal to a breast cancer malignant state remains unknown. To address this, we conducted an analysis combining Hi-C data with lamina-associated domains (LADs), epigenomic marks, and gene expression in an in vitro model of breast cancer progression. Our results reveal that while the fundamental properties of topologically associating domains (TADs) are overall maintained, significant changes occur in the organization of compartments and subcompartments. These changes are closely correlated with alterations in the expression of oncogenic genes. We also observe a restructuring of TAD-TAD interactions, coinciding with a loss of spatial compartmentalization and radial positioning of the 3D genome. Notably, we identify a previously unrecognized interchromosomal insertion event, wherein a locus on chromosome 8 housing the MYC oncogene is inserted into a highly active subcompartment on chromosome 10. This insertion is accompanied by the formation of de novo enhancer contacts and activation of MYC, illustrating how structural genomic variants can alter the 3D genome to drive oncogenic states. In summary, our findings provide evidence for the loss of genome organization at multiple scales during breast cancer progression revealing novel relationships between genome 3D structure and oncogenic processes.

genomics↗

bioRxiv2019

Unrestrained ESCRT-III drives chromosome fragmentation and micronuclear catastrophe

The ESCRT-III membrane fission machinery1,2 restores nuclear envelope integrity during mitotic exit3,4 and interphase5,6. Whereas primary nuclei resealing takes minutes, micronuclear envelope ruptures appear irreversible and result in catastrophic collapse associated with chromosome fragmentation and rearrangements (chromothripsis), thought to be a major driving force in cancer development7-10. Despite its importance11-13, the mechanistic underpinnings of nuclear envelope sealing in primary nuclei and the defects observed in micronuclei remain largely unknown. Here we show that CHMP7, the nucleator of ESCRT-III filaments at the nuclear envelope3,14, and the inner nuclear membrane protein LEMD215 act as a compartmentalization sensor detecting the loss of nuclear integrity. In cells with intact nuclear envelope, CHMP7 is actively excluded from the nucleus to preclude its binding to LEMD2. Nuclear influx of CHMP7 results in stable association with LEMD2 at the inner nuclear membrane that licenses local polymerization of ESCRT-III. Tight control of nuclear CHMP7 levels is critical, as induction of nuclear CHMP7 mutants is sufficient to induce unrestrained growth of ESCRT-III foci at the nuclear envelope, causing dramatic membrane deformation, local DNA torsional stress, single-stranded DNA formation and fragmentation of the underlying chromosomes. At micronuclei, membrane rupture is not associated with repair despite timely recruitment of ESCRT-III. Instead, micronuclei inherently lack the capacity to restrict accumulation of CHMP7 and LEMD2. This drives unrestrained ESCRT-III recruitment, membrane deformation and DNA defects that strikingly resemble those at primary nuclei upon induction of nuclear CHMP7 mutants. Preventing ESCRT-III recruitment suppresses membrane deformation and DNA damage, without restoring nucleocytoplasmic compartmentalization. We propose that the ESCRT-III nuclear integrity surveillance machinery is a double-edged sword, as its exquisite sensitivity ensures rapid repair at primary nuclei while causing unrestrained polymerization at micronuclei, with catastrophic consequences for genome stability16-18.

cell biology↗