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"Binetti, Ana G."
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The person-to-person transmission landscape of the gut and oral microbiomes
2023
The human microbiome is an integral component of the human body and a co-determinant of several health conditions
1
,
2
. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown
3
,
4
. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies
5
, especially those on non-infectious, microbiome-associated diseases.
Data from more than 9,700 human stool and oral metagenomes has been used to decipher the strain transmission patterns of the human microbiome from mother to infant, within households and within populations.
Journal Article
Protective Role of Limosilactobacillus fermentum Lf2 and Its Exopolysaccharides (EPS) in a TNBS-Induced Chronic Colitis Mouse Model
by
Irazoqui, José M.
,
Puntillo, Melisa
,
Burns, Patricia
in
antioxidant enzymes
,
Bacteria
,
Butyric acid
2024
Limosilactobacillus fermentum Lf2 (Lf2) is an autochthonous strain that produces high levels of exopolysaccharides (EPS). The objective of this work was to evaluate the probiotic potential of Lf2 and its relationship with these metabolites in a mouse model of TNBS (trinitrobenzene sulfonic acid)-induced chronic colitis. Mice were treated intrarectally with increasing doses of TNBS resuspended in 50% ethanol for 14 days. In parallel, they received different treatments by gavage (lactose 10% as the matrix): freeze-dried Lf2 (L); purified EPS (E); and lactose 10% (T). A healthy control group (H) was treated with 50% alcohol without TNBS (intrarectally) and 10% lactose (by gavage). In the small intestine, there was a significant increase in IgA levels for the group that received EPS and a decrease in IFN-γ for mice treated with the strain compared to the other groups. In the large intestine, IL-2 and IFN-γ presented the lowest levels in the groups treated with EPS and the strain. The concentrations of acetic and propionic acids in mice that received Lf2 were the highest, while the levels of butyric acid were comparable to the healthy control group. An increase in the abundance of SCFA-producing bacteria was observed for mice treated with EPS and the strain in comparison with the colitis control group. The enzyme activity of catalase was higher in all the treatments compared to the TNBS-induced colitis control mice. To summarize the results obtained, a principal component analysis (PCA) was performed, clearly grouping the treatments in different clusters according to the variables studied. This is one of the first studies to address the role of a potential probiotic strain in a chronic colitis mouse model, trying to elucidate the relationship between its properties and the EPS synthesized.
Journal Article
Elucidating the Connection Between the Health-Promoting Properties of Limosilactobacillus fermentum Lf2 and Its Exopolysaccharides
by
Olivar, Gabriela Correa
,
Irazoqui, José M.
,
Amadio, Ariel F.
in
Antioxidants
,
Bacteria
,
Composition
2025
The potential probiotic properties of Limosilactobacillus fermentum Lf2, an exopolysaccharide (EPS)-producing strain, were assessed in C57BL/6 mice. The aim of this work was to elucidate if these properties could be associated with the ability to produce EPSs. Mice were divided into three treatments: L (mice treated with Lf2), E (animals that received EPSs), and C (control group). The levels of fecal acetic and propionic acids significantly increased in L and E compared with C. Catalase activity increased in L in comparison with the other groups in the liver and small intestine. The enzyme activities of superoxide dismutase and glutathione S-transferase increased in the large intestine for L compared with C. In addition, in the large intestine, the concentration of TNF-α was reduced in L and E in comparison with C. In the small intestine, TNF-α, IFN-γ, IL-12, and IL-6 presented lower levels in L and E than C. The analysis of the gut microbiota showed that L presented higher levels of Peptococcaceae and Rikenellaceae, while E had higher levels of Peptococcaceae than C. Overall, these results provide new insights into the relationship between the probiotic properties of lactic acid bacteria and their ability to produce EPSs.
Journal Article
Exopolysaccharide from Lactobacillus fermentum Lf2 and its functional characterization as a yogurt additive
by
Perezlindo, Marcos J
,
Binetti, Ana G
,
Tabacman, Eduardo
in
animal models
,
Animals
,
exopolysaccharides
2016
Lactobacillus fermentum Lf2 is a strain which is able to produce high levels (approximately 1 g/l) of crude exopolysaccharide (EPS) when it is grown in optimised conditions. The aim of this work was to characterize the functional aspects of this EPS extract, focusing on its application as a dairy food additive. Our findings are consistent with an EPS extract that acts as moderate immunomodulator, modifying s-IgA and IL-6 levels in the small intestine when added to yogurt and milk, respectively. Furthermore, this EPS extract, in a dose feasible to use as a food additive, provides protection against Salmonella infection in a murine model, thus representing a mode of action to elicit positive health benefits. Besides, it contributes to the rheological characteristics of yogurt, and could function as a food additive with both technological and functional roles, making possible the production of a new functional yogurt with improved texture.
Journal Article
Protective Role of ILimosilactobacillus fermentum/I Lf2 and Its Exopolysaccharides in a TNBS-Induced Chronic Colitis Mouse Model
by
Peralta, Guillermo H
,
Puntillo, Melisa
,
Burns, Patricia
in
Chemical properties
,
Health aspects
,
Lactobacillus
2024
Limosilactobacillus fermentum Lf2 (Lf2) is an autochthonous strain that produces high levels of exopolysaccharides (EPS). The objective of this work was to evaluate the probiotic potential of Lf2 and its relationship with these metabolites in a mouse model of TNBS (trinitrobenzene sulfonic acid)-induced chronic colitis. Mice were treated intrarectally with increasing doses of TNBS resuspended in 50% ethanol for 14 days. In parallel, they received different treatments by gavage (lactose 10% as the matrix): freeze-dried Lf2 (L); purified EPS (E); and lactose 10% (T). A healthy control group (H) was treated with 50% alcohol without TNBS (intrarectally) and 10% lactose (by gavage). In the small intestine, there was a significant increase in IgA levels for the group that received EPS and a decrease in IFN-γ for mice treated with the strain compared to the other groups. In the large intestine, IL-2 and IFN-γ presented the lowest levels in the groups treated with EPS and the strain. The concentrations of acetic and propionic acids in mice that received Lf2 were the highest, while the levels of butyric acid were comparable to the healthy control group. An increase in the abundance of SCFA-producing bacteria was observed for mice treated with EPS and the strain in comparison with the colitis control group. The enzyme activity of catalase was higher in all the treatments compared to the TNBS-induced colitis control mice. To summarize the results obtained, a principal component analysis (PCA) was performed, clearly grouping the treatments in different clusters according to the variables studied. This is one of the first studies to address the role of a potential probiotic strain in a chronic colitis mouse model, trying to elucidate the relationship between its properties and the EPS synthesized.
Journal Article
Natural milk cultures for the production of Argentinian cheeses
by
Binetti, A.G
,
Giraffa, G
,
Reinheimer, J.A. (Universidad Nacional del Litoral, Santiago del Estero, Argentina.)
in
Animals
,
ARGENTINA
,
ARGENTINE
1997
Samples (32) of natural milk cultures used in the Santa Fe, Argentina, area for soft and semihard cheese production were examined. The microbial composition (including flora characterization) and technological parameters, (acidifying and proteolytic activities) were evaluated. The cultures contained mainly thermophilic lactic acid bacteria, identified as Streptococcus salivarius subsp. thermophilus (96.8% of the total strains) and Enterococcus spp. The strains showed a low proteolytic activity. The isolates of S. salivarius subsp. thermophilus exhibited a widespread phage resistance. The nonlactic microflora comprised coliforms, yeasts, spore-forming bacteria and lactate fermentative bacteria. The samples showed an acidity level from 0.38 to 0.69% lactic acid (pH from 4.25 to 5.75). The acidifying activity was optimal at 45 degrees C. The advantages and disadvantages of the employment of natural milk starters are discussed
Journal Article
Evidence for the Modulation of the Immune Response in Peripheral Blood Mononuclear Cells after Stimulation with a High Molecular Weight -glucan Isolated from Lactobacillus fermentum Lf2
by
Hafiz Ibrahim Ahmed
,
Vitlic, Ana
,
Binetti, Ana G
in
CD14 antigen
,
Exopolysaccharides
,
Immune response
2018
Lactobacillus fermentum Lf 2 produces large amounts of exopolysaccharides under optimized conditions (~2 g/L, EPS) which have been shown to possess immunomodulatory activity. In this study, the crude EPS was fractionated to give a high molecular weight (HMw) homoglycan and a mixture of medium molecular weight heteroglycans. The HMw EPS was isolated and identified as a -glucan. Peripheral blood mononuclear cells (PBMC) were pre-treated with purified polysaccharide to determine if the HMw -glucan is responsible for the immunomodulatory activity. Cells were also stimulated with either lipopolysaccharide (LPS) or phytohemagglutinin (PHA) and their effects, both with and without -glucan pre-treatment, compared. Exposure of the cells to -glucan increased their metabolic activity and whilst a small but statistically significant drop in CD14 expression was observed at Day 1, the levels were significantly elevated at Day 2. High levels of CD14 expression were observed in cells initially exposed to the -glucan and subsequently stimulated with either LPS or PHA. In contrast, reduced levels of TLR-2 expression were observed for cells initially exposed to the -glucan and subsequently stimulated with LPS. TNF- levels were elevated in -glucan treated cells (Day1) with the levels dropping back once the -glucan had been removed (Day 2). The stimulants LPS and PHA both induced significant rises in TNF- levels, however, this induction was completely (LPS) or partially blocked (PHA) in -glucan pre-treated cells. The results indicate a role for the bacterial -glucan in modulating the immune response following exposure to agonists such as bacterial LPS.
Evidence for the Modulation of the Immune Response in Peripheral Blood Mononuclear Cells after Stimulation with a High Molecular Weight β-glucan Isolated from Lactobacillus fermentum Lf2
2018
Lactobacillus fermentum Lf 2 produces large amounts of exopolysaccharides under optimized conditions (∼2 g/L, EPS) which have been shown to possess immunomodulatory activity. In this study, the crude EPS was fractionated to give a high molecular weight (HMw) homoglycan and a mixture of medium molecular weight heteroglycans. The HMw EPS was isolated and identified as a β-glucan.
Peripheral blood mononuclear cells (PBMC) were pre-treated with purified polysaccharide to determine if the HMw β-glucan is responsible for the immunomodulatory activity. Cells were also stimulated with either lipopolysaccharide (LPS) or phytohemagglutinin (PHA) and their effects, both with and without β-glucan pre-treatment, compared.
Exposure of the cells to β-glucan increased their metabolic activity and whilst a small but statistically significant drop in CD14 expression was observed at Day 1, the levels were significantly elevated at Day 2. High levels of CD14 expression were observed in cells initially exposed to the β-glucan and subsequently stimulated with either LPS or PHA. In contrast, reduced levels of TLR-2 expression were observed for cells initially exposed to the β-glucan and subsequently stimulated with LPS.
TNF-α levels were elevated in β-glucan treated cells (Day1) with the levels dropping back once the β-glucan had been removed (Day 2). The stimulants LPS and PHA both induced significant rises in TNF-α levels, however, this induction was completely (LPS) or partially blocked (PHA) in β-glucan pre-treated cells.
The results indicate a role for the bacterial β-glucan in modulating the immune response following exposure to agonists such as bacterial LPS.
Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers
by
Rademakers, Rosa
,
Graff, Caroline
,
Dopper, Elise G.
in
Biomarkers
,
Dementia
,
Neurodegeneration
2018
Objective To evaluate poly(GP), a dipeptide repeat protein, and neurofilament light chain (NfL) as biomarkers in presymptomatic C9orf72 repeat expansion carriers and patients with C9orf72‐associated frontotemporal dementia. Additionally, to investigate the relationship of poly(GP) with indicators of neurodegeneration as measured by NfL and grey matter volume. Methods We measured poly(GP) and NfL levels in cerebrospinal fluid (CSF) from 25 presymptomatic C9orf72 expansion carriers, 64 symptomatic expansion carriers with dementia, and 12 noncarriers. We explored associations with grey matter volumes using region of interest and voxel‐wise analyses. Results Poly(GP) was present in C9orf72 expansion carriers and absent in noncarriers (specificity 100%, sensitivity 97%). Presymptomatic carriers had lower poly(GP) levels than symptomatic carriers. NfL levels were higher in symptomatic carriers than in presymptomatic carriers and healthy noncarriers. NfL was highest in patients with concomitant motor neuron disease, and correlated with disease severity and survival. Associations between poly(GP) levels and small grey matter regions emerged but did not survive multiple comparison correction, while higher NfL levels were associated with atrophy in frontotemporoparietal cortices and the thalamus. Interpretation This study of C9orf72 expansion carriers reveals that: (1) poly(GP) levels discriminate presymptomatic and symptomatic expansion carriers from noncarriers, but are not associated with indicators of neurodegeneration; and (2) NfL levels are associated with grey matter atrophy, disease severity, and shorter survival. Together, poly(GP) and NfL show promise as complementary biomarkers for clinical trials for C9orf72‐associated frontotemporal dementia, with poly(GP) as a potential marker for target engagement and NfL as a marker of disease activity and progression.
Journal Article