scholarly journals Supplementation with Combined Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 Across Development Reveals Sex Differences in Physiological and Behavioural Effects of Western Diet in Long–Evans Rats

2020 ◽  
Vol 8 (10) ◽  
pp. 1527
Author(s):  
Elizabeth M. Myles ◽  
M. Elizabeth O’Leary ◽  
Rylan Smith ◽  
Chad W. MacPherson ◽  
Alexandra Oprea ◽  
...  
Keyword(s):  
Sex Differences ◽  
Early Life ◽  
Bifidobacterium Longum ◽  
Western Diet ◽  
Lactobacillus Helveticus ◽  
Calorie Intake ◽  
Dependent Manner ◽  
Probiotic Treatment ◽  
Long Evans ◽  
Diet Exposure

The gut microbiome affects various physiological and psychological processes in animals and humans, and environmental influences profoundly impact its composition. Disorders such as anxiety, obesity, and inflammation have been associated with certain microbiome compositions, which may be modulated in early life. In 62 Long–Evans rats, we characterised the effects of lifelong Bifidobacterium longum R0175 and Lactobacillus helveticus R0052 administration—along with Western diet exposure—on later anxiety, metabolic consequences, and inflammation. We found that the probiotic formulation altered specific anxiety-like behaviours in adulthood. We further show distinct sex differences in metabolic measures. In females, probiotic treatment increased calorie intake and leptin levels without affecting body weight. In males, the probiotic seemed to mitigate the effects of Western diet on adult weight gain and calorie intake, without altering leptin levels. The greatest inflammatory response was seen in male, Western-diet-exposed, and probiotic-treated rats, which may be related to levels of specific steroid hormones in these groups. These results suggest that early-life probiotic supplementation and diet exposure can have particular implications on adult health in a sex-dependent manner, and highlight the need for further studies to examine the health outcomes of probiotic treatment in both sexes.

scholarly journals Probiotic Colonization of the Adherent Mucus Layer of HT29MTXE12 Cells Attenuates Campylobacter jejuni Virulence Properties

2010 ◽  
Vol 78 (6) ◽  
pp. 2812-2822 ◽  
Author(s):  
Abofu Alemka ◽  
Marguerite Clyne ◽  
Fergus Shanahan ◽  
Thomas Tompkins ◽  
Nicolae Corcionivoschi ◽  
...  
Keyword(s):  
Cell Line ◽  
Campylobacter Jejuni ◽  
Bifidobacterium Longum ◽  
Early Time ◽  
Lactobacillus Helveticus ◽  
Mucus Layer ◽  
Junction Protein ◽  
Probiotic Treatment ◽  
Virulence Properties

ABSTRACT The HT29MTXE12 (E12) cell line harbors an adherent mucus layer, providing a novel technique to model mucosal infection in vitro. In this study, we have characterized the interaction of Campylobacter jejuni with the E12 cell line and exploited its unique mucus layer to examine the potential efficacy of probiotic treatment to attenuate C. jejuni virulence properties. C. jejuni 81-176 colonized and reproduced in E12 mucus. Adhesion to and internalization of C. jejuni were enhanced in E12 cells harboring mucus compared to parental cells without mucus. Translocation of C. jejuni occurred at early time points following infection. C. jejuni aligned with tight junctions and colocalized with the tight junction protein occludin, suggesting a paracellular route of translocation. Probiotic strains Lactobacillus rhamnosus R0011, Lactobacillus helveticus R0052, Lactobacillus salivarius AH102, Bifidobacterium longum AH1205, a commercial combination of L. rhamnosus R0011 and L. helveticus R0052 (Lacidofil), and a cocktail consisting of L. rhamnosus, L. helveticus, and L. salivarius (RhHeSa) colonized E12 mucus and bound to underlying cells. Probiotics attenuated C. jejuni association with and internalization into E12 cells and translocation to the basolateral medium of transwells. Live bacteria and prolonged precolonization of E12 cells with probiotics were necessary for probiotic action. These results demonstrate the potential for E12 cells as a model of mucosal pathogenesis and provide a rationale for the further investigation of probiotics as prophylaxis against human campylobacteriosis.

scholarly journals Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut

2021 ◽  
Author(s):  
Martin F. Laursen ◽  
Mikiyasu Sakanaka ◽  
Nicole von Burg ◽  
Urs Mörbe ◽  
Daniel Andersen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Early Life ◽  
Bifidobacterium Longum ◽  
Aromatic Amino Acids ◽  
Dependent Manner ◽  
Microbial Metabolites ◽  
Phenyllactic Acid ◽  
Lactic Acids

AbstractBreastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum. We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4+ T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA3). Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.

scholarly journals Ingestion of probiotic (Lactobacillus helveticus and Bifidobacterium longum) alters intestinal microbial structure and behavioral expression following social defeat stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katherine A. Partrick ◽  
Anna M. Rosenhauer ◽  
Jérémie Auger ◽  
Amanda R. Arnold ◽  
Nicole M. Ronczkowski ◽  
...  
Keyword(s):  
Social Stress ◽  
Bifidobacterium Longum ◽  
Social Defeat ◽  
Lactobacillus Helveticus ◽  
Rrna Gene ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Microbial Structure ◽  
Microbial Composition ◽  
Anti Inflammatory

AbstractSocial stress exacerbates anxious and depressive behaviors in humans. Similarly, anxiety- and depressive-like behaviors are triggered by social stress in a variety of non-human animals. Here, we tested whether oral administration of the putative anxiolytic probiotic strains Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces the striking increase in anxiety-like behavior and changes in gut microbiota observed following social defeat stress in Syrian hamsters. We administered the probiotic at two different doses for 21 days, and 16S rRNA gene amplicon sequencing revealed a shift in microbial structure following probiotic administration at both doses, independently of stress. Probiotic administration at either dose increased anti-inflammatory cytokines IL-4, IL-5, and IL-10 compared to placebo. Surprisingly, probiotic administration at the low dose, equivalent to the one used in humans, significantly increased social avoidance and decreased social interaction. This behavioral change was associated with a reduction in microbial richness in this group. Together, these results demonstrate that probiotic administration alters gut microbial composition and may promote an anti-inflammatory profile but that these changes may not promote reductions in behavioral responses to social stress.

scholarly journals Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  
Keyword(s):  
Sex Differences ◽  
Microbial Activity ◽  
Hepatic Steatosis ◽  
Female Rats ◽  
Male Rats ◽  
Calorie Intake ◽  
Dietary Copper ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rrna Sequencing

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.

P.207 Sex differences in cocaine consumption vulnerability induced by early-life stress in mice

2021 ◽  
Vol 44 ◽  
pp. S20-S21
Author(s):  
A. Castro-Zavala ◽  
A. Martín-Sánchez ◽  
L. Montalvo-Martínez ◽  
A. Camacho-Morales ◽  
O. Valverde
Keyword(s):  
Sex Differences ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

scholarly journals Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner

2021 ◽  
Vol 22 (4) ◽  
pp. 1899 ◽  
Author(s):  
Hae Jeong Park ◽  
Sang A. Kim ◽  
Won Sub Kang ◽  
Jong Woo Kim
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Male And Female Rats

Recent studies have reported that changes in gut microbiota composition could induce neuropsychiatric problems. In this study, we investigated alterations in gut microbiota induced by early-life stress (ELS) in rats subjected to maternal separation (MS; 6 h a day, postnatal days (PNDs) 1–21), along with changes in inflammatory cytokines and tryptophan-kynurenine (TRP-KYN) metabolism, and assessed the differences between sexes. High-throughput sequencing of the bacterial 16S rRNA gene showed that the relative abundance of the Bacteroides genus was increased and that of the Lachnospiraceae family was decreased in the feces of MS rats of both sexes (PND 56). By comparison, MS increased the relative abundance of the Streptococcus genus and decreased that of the Staphylococcus genus only in males, whereas the abundance of the Sporobacter genus was enhanced and that of the Mucispirillum genus was reduced by MS only in females. In addition, the levels of proinflammatory cytokines were increased in the colons (IFN-γ and IL-6) and sera (IL-1β) of the male MS rats, together with the elevation of the KYN/TRP ratio in the sera, but not in females. In the hippocampus, MS elevated the level of IL-1β and the KYN/TRP ratio in both male and female rats. These results indicate that MS induces peripheral and central inflammation and TRP-KYN metabolism in a sex-dependent manner, together with sex-specific changes in gut microbes.

scholarly journals Bifidobacterium bifidum R0071 results in a greater proportion of healthy days and a lower percentage of academically stressed students reporting a day of cold/flu: a randomised, double-blind, placebo-controlled study

2015 ◽  
Vol 113 (3) ◽  
pp. 426-434 ◽  
Author(s):  
Bobbi Langkamp-Henken ◽  
Cassie C. Rowe ◽  
Amanda L. Ford ◽  
Mary C. Christman ◽  
Carmelo Nieves ◽  
...  
Keyword(s):  
Acute Stress ◽  
Bifidobacterium Longum ◽  
Daily Intake ◽  
Bifidobacterium Bifidum ◽  
Lactobacillus Helveticus ◽  
Lower Percentage ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Symptom Intensity

Acute psychological stress is positively associated with a cold/flu. The present randomised, double-blind, placebo-controlled study examined the effect of three potentially probiotic bacteria on the proportion of healthy days over a 6-week period in academically stressed undergraduate students (n 581) who received Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium bifidum R0071 or placebo. On each day, participants recorded the intensity (scale: 0 = not experiencing to 3 = very intense) for nine cold/flu symptoms, and a sum of symptom intensity >6 was designated as a day of cold/flu. B. bifidum resulted in a greater proportion of healthy days than placebo (P≤ 0·05). The percentage of participants reporting ≥ 1 d of cold/flu during the 6-week intervention period was significantly lower with B. bifidum than with placebo (P< 0·05). There were no effects of B. infantis or L. helveticus compared with placebo on either outcome. A predictive model accounted for influential characteristics and their interactions on daily reporting of cold/flu episodes. The proportion of participants reporting a cold on any given day was lower at weeks 2 and 3 with B. bifidum and B. infantis than with placebo for the average level of stress and the most commonly reported number of hours of sleep. Daily intake of bifidobacteria provides benefit related to cold/flu outcomes during acute stress.

Abstract 272: Sex Differences in β-Adrenergic Responsiveness of Excitation-Contraction Coupling in Isolated Rabbit Hearts

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Gregory Hoeker ◽  
Ashleigh Hood ◽  
Rodolphe Katra ◽  
Steven Poelzing ◽  
Steven Pogwizd
Keyword(s):  
Sex Differences ◽  
Action Potentials ◽  
Adrenergic Receptor ◽  
Calcium Release ◽  
Dependent Manner ◽  
Ectopic Activity ◽  
Dose Threshold ◽  
Ectopic Beats ◽  
Cardioprotective Effects ◽  
Dose Dependent

Introduction: Sex differences in β-adrenergic receptor (β-AR) responsiveness are associated with female cardioprotection. We hypothesize that female (F) rabbits have reduced responsiveness to β-AR stimulation vs males (M), and that the degree and type of sex differences vary with the β-AR subtypes that are activated. Methods: Ventricular action potentials (AP) and intracellular calcium transients (CaT) were optically mapped from the epicardial surface of rabbit hearts during 3 Hz pacing. Spontaneous calcium release (SCR) and ectopic activity were elicited at 1, 3, and 5.5 Hz. β-responsiveness was assessed with the nonselective β-agonist isoproterenol (Iso, 1-316 nM), or β2-AR selective agonist zinterol (Zin, 10 nM). Results: At baseline, the time constant of CaT decay (τ) was faster in F than M (54.0±1.7 vs 62.1±3.0 ms; n=14, 14; p < 0.05), with no sex difference in CaT duration (CaD80). AP duration (APD90) was shorter in F than M (202.5±5.0 vs 218.2±5.7 ms; p < 0.05). Iso decreased τ, CaD80, and APD90 in a dose-dependent manner in both sexes (n = 5, 5 for F, M). Iso decreased τ to a lesser extent in F than M for 1 and 32-316 nM Iso (F = 11-32 ms, M = 23-48 ms; p < 0.05). The Iso-induced decrease in CaD80 was not significantly different in F than M at any dose. The Iso-induced decrease in APD90 was significantly less in F than M only at 316 nM Iso (75.5±8.7 ms vs 103.9±6.2 ms, p < 0.05). In contrast, there were no sex differences in the response to Zin for τ, CaD80, or APD90 (n = 6, 6 for F, M). Zin decreased τ by 7.2±2.0 ms in F vs 12.7±3.7 ms in M; CaD80 by 18.0±5.3% in F vs 21.1±8.0 ms in M; and APD90 by 24.9±8.5 ms in F vs 21.9±8.9 ms in M. SCR was observed in 50% (6/12) of hearts treated with Zin, whereas Iso elicited SCR in all hearts (10/10) with a dose threshold of 32 nM. No ectopic beats were observed with Zin (0/36 trials in 12 hearts). With Iso, ectopic activity was less frequent in F hearts (16%, 12/75 trials in 5 hearts) than in M hearts (41%, 26/68 trials in 5 hearts, p < 0.05). Conclusions: These results suggest that sex differences in AP and CaT depend on the dose of the agonist used and the β-AR subtypes that are activated. Elucidating nuances of sex differences in β-AR subtype physiology will provide a better understanding of the mechanisms of reduced β-responsiveness in F and its cardioprotective effects.

Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jessilyn Dunn ◽  
Haiwei Qiu ◽  
Soyeon Kim ◽  
Daudi Jjingo ◽  
Ryan Hoffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Western Diet ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

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