Female Microbiota Research Articles

P177 MICROBIAL TRYPTOPHAN-INDOLE PATHWAY REGULATES BLOOD PRESSURE (BP) IN A SEX SPECIFIC MANNER

Introduction: Aberrant tryptophan absorption promotes hypertension as gut microbiota converts tryptophan to pro-hypertensive indole. Intestinal Ace2 regulates tryptophan homeostasis, but its role in salt-sensitive hypertension is unknown. Ace2 functions differently in males and females. Therefore, we hypothesized that sex-specific intestinal ACE2 dependent transport of tryptophan contributes to salt-sensitive hypertension via microbiota-indole axis. Methods: 10-week-old Dahl salt-sensitive (S) rats and novel Ace2 KO S rats of both sexes were maintained on either a low (LS) or high (HS) salt diet for 21 days. BP was measured by radiotelemetry. Gut microbiota and indole were analyzed. Results: Mean arterial BP of S Ace2 KO rats on LS was elevated in females by 38 mmHg (SAce2KO 170 ± 10 vs. S 132 ± 3; P=0.0028) and in males by 18 mmHg (SAce2KO 140 ± 6 vs. S 122 ± 1.5; P=0.01), and further elevated on HS by 68 mmHg in females (SAce2KO 211 ± 14 vs. S 143 ± 4.5; P=0.0003) and by 40 mmHg in males (SAce2KO 182 ± 9 vs. S 142 ± 3; P=0.0009). These were associated with elevated serum indole mainly in male SAce2KO rats, compared to S rats on both LS (1.2 ± 0.2 vs. 0.3 ± 0.2 μM; P=0.02) and HS (1.5 ± 0.25 vs. 0.2 ± 0.03 μM; P=0.0001). Microbiota analysis revealed significant shifts in β-diversity in Ace2 KO rats of both sexes with more changes in HS males; and Ace2 KO induced more tryptophan-utilizing, indole-producing bacteria Escherichia-Shigella in males on both LS (P<0.05) and HS (P<0.0001). Strikingly, none of these differences were found in females. Conclusions: Lack of Ace2 increased BP regardless of sex and salt. In males, Ace2 KO increased indole levels and abundance of Escherichia-Shigella. Microbial changes by salt and ACE2 KO were found mainly in males, suggesting a more resilient microbiota in females. Thus, the microbiota-indole axis may be a therapeutic target for BP control in males with altered tryptophan metabolism.

A Mix of Potentially Probiotic Limosilactobacillus fermentum Strains Alters the Gut Microbiota in a Dose- and Sex-Dependent Manner in Wistar Rats.

Multi-strain Limosilactobacillus (L.) fermentum is a potential probiotic with reported immunomodulatory properties. This study aimed to evaluate the composition, richness, and diversity of the gut microbiota in male and female rats after treatment with a multi-strain of L. fermentum at different doses. Thirty rats (fifteen male and fifteen female) were allocated into a control group (CTL), a group receiving L. fermentum at a dose of 108 CFU (Lf-108), and a group receiving L. fermentum at a dose of 1010 CFU (Lf-1010) for 13 weeks. Gut microbiota and serum cytokine levels were evaluated after L. fermentum treatment. Male CTL rats had a lower relative abundance of Bifidobacteriaceae and Prevotella and a lower alpha diversity than their female CTL counterparts (p < 0.05). In addition, male CTL rats had a higher Firmicutes/Bacteroidetes (F/B) ratio than female CTL rats (p < 0.05). In female rats, the administration of L. fermentum at 108 CFU decreased the relative abundance of Bifidobacteriaceae and Anaerobiospirillum and increased Lactobacillus (p < 0.05). In male rats, the administration of L. fermentum at 1010 CFU decreased the F/B ratio and increased Lachnospiraceae and the diversity of the gut microbiota (p < 0.05). The relative abundance of Lachnospiraceae and the alpha-diversity of gut microbiota were negatively correlated with serum levels of IL1β (r = -0.44) and TNFα (r = -0.39), respectively. This study identified important changes in gut microbiota between male and female rats and showed that a lower dose of L. fermentum may have more beneficial effects on gut microbiota in females, while a higher dose may result in more beneficial effects on gut microbiota in male rats.

Abstract 082: Dysregulated Microbiota-indole Axis In Male, Not Female Ace2 Deficient Salt-sensitive Hypertension

Introduction: Aberrant tryptophan (Trp) absorption may promote hypertension (HTN) due to gut microbiota converting Trp to pro-hypertensive indoles. Intestinal Ace2 regulates Trp homeostasis, but its role in salt-sensitive HTN is unknown. Further, lack of Ace2 can affect males and females differently because Ace2 is transcribed from the X-chromosome in a genomic region which escapes X-inactivation. Therefore, we hypothesized that sex-specific intestinal ACE2 dependent transport of Trp contributes to salt-sensitive HTN via the microbiota-indole axis. Methodology: 8-10-week-old Dahl salt-sensitive (S) rats and newly generated CRISPR/Cas9 Ace2 deficient S rats of both sexes (N= 7 rats/group) were maintained on either a low (0.3 % NaCl, LS) or high (2 % NaCl, HS) salt diet for 21 days. BP was measured by radiotelemetry for 24 hours on day 21. Serum and cecal content were collected for indole measurement and microbiota analysis. Results: Mean arterial BP of S Ace2 deficient rats on LS was elevated in females by 38 mmHg (S Ace2 -/- 170 ± 10 vs. S 132 ± 3; P =0.0028) and in males by 18 mmHg (S Ace2 -/Y 140 ± 6 vs. S 122 ± 1.5; P =0.01), and further elevated on HS by 68 mmHg in females (S Ace2-/- 211 ± 14 vs. S 143 ± 4.5; P =0.0003) and by 40 mmHg in males (S Ace2-/Y 182 ± 9 vs. S 142 ± 3; P =0.0009). These were associated with elevated serum indole levels mainly in male S Ace2 -/Y rats, compared to S rats on both LS (1.2 ± 0.2 vs. 0.3 ± 0.2 μM; P =0.02) and HS (1.5 ± 0.25 vs. 0.2 ± 0.03 μM; P =0.0001). Microbiota analysis revealed (1) significant shifts in β-diversity in Ace2 deficient rats of both sexes with a higher R value and a lower P value in HS males; (2) Ace2 deficiency resulted in higher abundance of Trp-utilizing, indole-producing bacteria Escherichia - Shigella in males on both LS ( P &lt;0.05) and HS ( P &lt;0.0001). Strikingly, none of these differences were found in females. Conclusion: Lack of Ace2 led to increased mean BP regardless of sex and salt intake. In males, Ace2 deficiency led to increased indole levels with higher abundance of Escherichia - Shigella . Overall microbial changes by salt and ACE2 deficiency were found mainly in males, suggesting a more resilient microbiota in females. Thus, the microbiota-indole axis may be a potential therapeutic target for BP control in males with altered Trp metabolism.

Metagenomic insights into the effects of cosmetics containing complex polysaccharides on the composition of skin microbiota in females.

The use of cosmetics has become a habit for women. However, their influence on the microbial diversity of the skin has rarely been studied. Herein, the effect of cosmetics containing complex polysaccharides on the skin bacterial microbiota of female forehead and cheek areas was analyzed. Eighty volunteers were recruited and split into two groups (40 people each); one group was treated with cosmetics containing complex polysaccharides and the other with basic cream for 28 days. Skin samples were collected using sterilized cotton swabs, and 16S rDNA high-throughput sequencing was used to analyze the changes in skin bacterial microbiota composition before and after the intervention. A total of twenty-four phyla were detected in the forehead and cheek skin samples of 80 volunteers, the top three of which were Proteobacteria, Firmicutes, and Actinobacteria. The main genera of the forehead skin bacterial microbiota were Cutibacterium (11.1%), Acinetobacter (10.4%), Enterococcus (8.9%), Ralstonia (8.8%), and Staphylococcus (8.7%), while those of the cheek skin bacterial microbiota were Staphylococcus (20.0%), Ralstonia (8.7%), Propionibacterium (7.9%), Acinetobacter (7.2%), and Bifidobacterium (6.0%). Compared with basic cream, the use of cosmetics containing complex polysaccharides significantly increased the relative abundance of Staphylococcus and Bacillus in the forehead and cheek and reduced the relative abundance of Propionibacterium and Bifidobacterium. Thus, cosmetics containing complex polysaccharides could modify the composition of skin bacterial microbiota, which may help to maintain stable conditions of the skin.

Decontamination protocols affect the internal microbiota of ticks

Studies on the microbiota of ticks have promoted hypotheses about the combined effects of the bacterial community, its functional contributions to the tick’s physiology or probable competition effects with some tick-borne pathogens. However, knowledge on the origin of the microbiota of newly hatched larvae is missing. This study aimed to elucidate the source(s) of the microbiota in unfed tick larvae, addressing the composition of the “core microbiota” and the best ways to decontaminate eggs for microbiota studies. We applied laboratory degree bleach washes and/or ultraviolet light treatments on engorged Rhipicephalus australis females and/or their eggs. No significant effects of these treatments on the reproductive parameters of females and the hatching rates of eggs were observed. However, the different treatments did show striking effects on the composition of the microbiota. The results indicated that bleach washes disrupted the internal tick microbiota in females, implying that bleach may have entered the tick and subsequently affected the microbiota. Furthermore, the analyses of results demonstrated that the ovary is a main source of tick microbiota, while the contribution of Gené’s organ (a part of the female reproductive system that secretes a protective wax coat onto tick eggs) or the male’s spermatophore requires further investigation. Further studies are needed to identify best practice protocols for the decontamination of ticks for microbiota studies.Graphical

Protective Effects of Female Gut Microbiota Transplantation on Hypertension and Renal Damage in Male Dahl Salt-Sensitive Rats

We have previously demonstrated through microbiota transplantation studies that the gut microbiota importantly contributes to the development of hypertension, renal damage, and renal inflammation in the Dahl Salt-Sensitive (SS) rat fed a 4.0% NaCl high salt diet (HS). We also know that female SS rats are significantly protected from salt-induced hypertension, renal injury, and renal immune cell infiltration compared to males. One potential explanation for this sex difference is the substantial divergence we have observed in gut microbiota composition between male and female SS rats. Therefore, we hypothesized that gut microbiota transplantation between males and females would modulate the observed sex differences in salt-sensitivity. At 8 weeks of age, we first suppressed the native gut microbiota of male SS rat recipients via broad-spectrum antibiotics treatment (bacitracin and streptomycin, 2 g each/L, p.o.) for 3 days, followed by inoculation with either male or female donor cecal contents (oral gavage, 1 mL) for 7 consecutive days. Thus, our experimental groups are 1) male recipient rats repopulated with male donor microbiota (M+M, n=4) and 2) male recipient rats repopulated with female donor microbiota (M+F, n=3). Donor rats were maintained on the 0.4% NaCl low salt diet (LS) to more closely mimic the intrinsic microbiota of each sex. Telemeters were implanted at 10 weeks to allow for the continuous monitoring of blood pressure, followed by 3 weeks of HS challenge. At baseline, there were no differences in mean arterial pressure (MAP) between groups (123.4±1.3 vs 124.5±3.6 mmHg, M+M vs M+F on HS day 0, p=0.765). However, during the last week of HS challenge, males receiving female cecal microbiota transplantation had significantly reduced MAP compared to controls (153.6±3.4 vs 144.1±4.8 mmHg, M+M versus M+F on HS day 19, p=0.013). At the conclusion of the study, this reduction in blood pressure also coincided with a protection from renal damage, indicated by reduced urinary albumin excretion (209.0±37.1 vs 143.7±19.2 mg/day, M+M vs M+F, p=0.035), and an improvement in renal function, indicated by an increase in creatinine clearance (0.36±0.02 vs 0.48±0.01 ml/min/g kidney, M+M vs M+F, p=0.002). However, there appeared to be no effects on renal inflammation, with no changes to either the circulating or renal immune cell profile between rats receiving male or female microbiota. Furthermore, in female SS rat recipients that were subsequently transplanted with either male or female donor cecal contents, we observed no significant effects related to sex of donor microbiota in terms of blood pressure, renal damage, or renal inflammation. Together, these data demonstrate the anti-hypertensive and renoprotective effects of the female gut microbiota to recipient male SS rats. Moreover, there are additional factors within the female host that appear to be protective against the male microbiota. 19CDA34660184, HL161231 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Intestinal lamina propria stromal cells function as the target of androgens and microbiota metabolites for the prevention of lupus.

Abstract The gut microbiota affects autoimmune diseases including lupus. We found that female and male microbiota in NZBxNZWF1 (BWF1) mice differ. Our goal is to understand the relationship between sex, microbiota and disease. Microbiota depletion in females has no impact on disease and female microbiota does not induce disease in males; male microbiota can protect female mice from disease while castrated male microbiota loses this ability (castration induces disease and alters the microbiota in males). Intestinal lamina propria stromal cells (LPSC) can affect microbiota and immunoregulation [via regulating CD103 dendritic cell (CD103DC) development and consequently, peripheral regulatory T cells (pTregs)]. CD103DC function and pTregs are both decreased in female and castrated male mice. Endogenous androgens directly induce genes, RALDH1and 2(i.e., retinoic acid production), TGFBand GM-CSF, in LPSC that are critical for CD103 development. Transferred male gut microbiota induce expression of the same genes in LPSC in female recipients that we determined was not due to androgens produced by the male microbiota, since no androgen response genes, ANGTLand CHRD, were induced in highly androgen-sensitive LPSC. The male microbiota metabolomic profile differs from either female or castrated male mice, and includes the RXR agonist metabolite(s), phytol/phytanic acid, that directly induce(s) LPSC to express RALDH1and 2, TGFBand GM-CSF. We propose that 1) endogenous androgens regulate CD103DC function and microbiota function through the LPSC in males; (2) male-modified microbiota produces metabolite(s) that may mediate protection in female recipients through the LPSC and subsequent restoration of CD103DC function and pTregs. Funded by a TIL grant from the Alliance for Lupus Research and the NIH (R01AR067188)

Gut and Vaginal Microbiota in the Endometriosis: Systematic Review and Meta-Analysis.

Endometriosis is a clinical condition associated with genetic, endocrine, and immunological factors, present in 6 to 10% of women of reproductive age. Currently, the human microbiota has been studied and associated with the evolution of diseases due to its influence on pathogenesis, indicating that changes in the colonization of microorganisms in the genitourinary and gastrointestinal systems can promote physiological changes that can trigger inflammatory and immunological processes and hormonal dysregulation, which can be linked to endometriosis. Thus, this systematic review and meta-analysis evaluated microbiota changes in women with endometriosis. The following electronic databases were searched up to April 2022: Medline, Embase, Web of Science, Cochrane Library, and gray literature (Google Scholar), using the keywords "dysbiosis", "microbiome" and "endometriosis", combined with their synonyms. The observational studies conducted with women diagnosed with endometriosis and women without endometriosis as controls were included. For the analyses, a standard mean difference with a 95% confidence interval was used using RevMan software (version 5.4), and for methodological quality assessment, the Newcastle-Ottawa scale was used. A total of 16 studies were found in the literature assessing the composition of the microbiota in women with endometriosis, and no significant difference were found for changes in alpha diversity analysis in gut microbiota (SMD = -0.28; 95% CI = -0.70 to 0.14; P = 0.19; I2 = 52%; four studies, 357 participants) or vaginal microbiota (SMD = -0.68; 95% CI = -1.72 to 0.35; P = 0.19; I2 = 66%; two studies, 49 participants). In intestinal and vaginal samples from women with endometriosis, alpha-diversity did not present a significant difference when compared to the control population. However, each study individually showed a possible relationship between the female microbiota and endometriosis. This trial is registered with CRD42021260972.

Influence of Sex on the Microbiota of the Human Face.

The role of the microbiota in health and disease has long been recognized and, so far, the cutaneous microbiota in humans has been widely investigated. The research regarded mainly the microbiota variations between body districts and disease skin states (i.e., atopic dermatitis, psoriasis, acne). In fact, relatively little information is available about the composition of the healthy skin microbiota. The cosmetic industry is especially interested in developing products that maintain and/or improve a healthy skin microbiota. Therefore, in the present work, the authors chose to investigate in detail the structure and composition of the basal bacterial community of the face. Ninety-six cheek samples (48 women and 48 men) were collected in the same season and the same location in central northern Italy. Bacterial DNA was extracted, the 16S rDNA gene was amplified by PCR, the obtained amplicons were subjected to next generation sequencing. The principal members of the community were identified at the genus level, and statistical analyses showed significant variations between the two sexes. This study identified abundant members of the facial skin microbiota that were rarely reported before in the literature and demonstrated the differences between male and female microbiota in terms of both community structure and composition.

Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation

Background and purposeStroke is associated with high disability and mortality rates and increases the incidence of organ-related complications. Research has revealed that the outcomes and prognosis of stroke are regulated by the state of the intestinal microbiota. However, the possibility that the manipulation of the intestinal microbiota can alter sex-related stroke outcomes remain unknown.MethodsTo verify the different effects of microbiota from different sexes on stroke outcomes, we performed mouse fecal microbiota transplantation (FMT) and established a model of ischemic stroke. Male and female mice received either male or female microbiota through FMT. Ischemic stroke was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control. Over the next few weeks, the mice underwent neurological evaluation and metabolite and inflammatory level detection, and we collected fecal samples for 16S ribosomal RNA analysis.ResultsWe found that when the female mice were not treated with FMT, the microbiota (especially the Firmicutes-to-Bacteroidetes ratio) and the levels of three main metabolites tended to resemble those of male mice after experimental stroke, indicating that stroke can induce an ecological imbalance in the biological community. Through intragastric administration, the gut microbiota of male and female mice was altered to resemble that of the other sex. In general, in female mice after MCAO, the survival rate was increased, the infarct area was reduced, behavioral test performance was improved, the release of beneficial metabolites was promoted and the level of inflammation was mitigated. In contrast, mice that received male microbiota were much more hampered in terms of protection against brain damage and the recovery of neurological function.ConclusionA female-like biological community reduces the level of systemic proinflammatory cytokines after ischemic stroke. Poor stroke outcomes can be positively modulated following supplementation with female gut microbiota.

Pubertal consumption of R. badensis subspecies acadiensis modulates LPS-induced immune responses and gut microbiome dysbiosis in a sex-specific manner

Puberty is a critical period of development characterized by significant brain remodeling and increased vulnerability to immune challenges. Exposure to an immune challenge such as LPS during puberty can result in inflammation and gut dysbiosis which may lead to altered brain functioning and psychiatric illnesses later in life. However, treatment with probiotics during puberty has been found to mitigate LPS-induced peripheral and central inflammation, prevent LPS-induced changes to the gut microbiota and protect against enduring behavioural disorders in a sex-specific manner. Recent findings from our laboratory revealed that pubertal R. badensis subspecies acadiensis (R. badensis subsp. acadiensis) treatment prevents LPS-induced depression-like behavior and alterations in 5HT1A receptor expression in a sex-specific manner. However, the underlying mechanism remains unclear. Thus, the aim of this study was to gain mechanistic insights and to investigate the ability of R. badensis subsp. acadiensis consumption during puberty to mitigate the effects of LPS treatment on the immune system and the gut microbiome. Our results revealed that pubertal treatment with R. badensis subsp. acadiensis reduced sickness behaviors in females more than males in a time-specific manner. It also mitigated LPS-induced increases in pro-inflammatory cytokines in the blood and in TNFα mRNA expression in the prefrontal cortex and the hippocampus of female mice. There were sex-dependent differences in microbiome composition that persisted after LPS injection or R. badensis subsp. acadiensis consumption. R. badensis subsp. acadiensis had greater impact on the microbiota of male mice but female microbiota’s were more responsive to LPS treatment. This suggested that female mice microbiota’s may be more prone to modulation by this probiotic. These findings emphasize the sex-specific effects of probiotic use during puberty on the structure of the gut microbiome and the immune system and highlight the critical role of gut colonization with probiotics during adolescence on immunomodulation and prevention of the enduring effects of infections.

Ovariectomy Impaired Hepatic Glucose and Lipid Homeostasis and Altered the Gut Microbiota in Mice With Different Diets.

The lower incidence of metabolic diseases of women than men and the increasing morbidity of metabolic disorders of menopausal women indicated that hormones produced by ovaries may affect homeostasis of glucose and lipid metabolism, but the underlying mechanisms remain unclear. To explore the functions of ovaries on regulating glucose and lipid metabolism in females, 8 weeks old C57BL/6 mice were preformed ovariectomy and administrated with normal food diet (NFD) or high fat diet (HFD). Six weeks after ovariectomy, blood biochemical indexes were tested and the morphology and histology of livers were checked. The expression levels of genes related to glucose and lipid metabolism in liver were detected through transcriptome analysis, qPCR and western blot assays. 16S rDNA sequence was conducted to analyze the gut microbiota of mice with ovariectomy and different diets. The serum total cholesterol (TC) was significantly increased in ovariectomized (OVX) mice fed with NFD (OVXN), and serum low density lipoprotein-cholesterol (LDL-C) was significantly increased in both OVXN mice and OVX mice fed with HFD (OVXH). The excessive glycogen storage was found in livers of 37.5% mice from OVXN group, and lipid accumulation was detected in livers of the other 62.5% OVXN mice. The OVXN group was further divided into OVXN-Gly and OVXN-TG subgroups depending on histological results of the liver. Lipid drops in livers of OVXH mice were more and larger than other groups. The expression level of genes related with lipogenesis was significantly increased and the expression level of genes related with β-oxidation was significantly downregulated in the liver of OVXN mice. Ovariectomy also caused the dysbiosis of intestinal flora of OVXN and OVXH mice. These results demonstrated that hormones generated by ovaries played important roles in regulating hepatic glucose and lipid metabolism and communicating with the gut microbiota in females.

Bugs and Brains, the Gut and Mental Health Study: a mixed-methods study investigating microbiota composition and function in anxiety, depression and irritable bowel syndrome

IntroductionResearch has highlighted relationships between the micro-organisms that inhabit our gastrointestinal tract (oral and gut microbiota) with host mood and gastrointestinal functioning. Mental health disorders and functional gastrointestinal disorders co-occur...

Differential responses of gut microbiota of male and female fathead minnow (Pimephales promelas) to a short-term environmentally-relevant, aqueous exposure to benzo[a]pyrene

In addition to aiding in digestion of food and uptake of nutrients, microbiota in guts of vertebrates are responsible for regulating several beneficial functions, including development of an organism and maintaining homeostasis. However, little is known about effects of exposures to chemicals on structure and function of gut microbiota of fishes. To assess effects of exposure to polycyclic aromatic hydrocarbons (PAHs) on gut microbiota, male and female fathead minnows (Pimephales promelas) were exposed to environmentally-relevant concentrations of the legacy PAH benzo[a]pyrene (BaP) in water. Measured concentrations of BaP ranged from 2.3 × 10−3 to 1.3 μg L−1. The community of microbiota in the gut were assessed by use of 16S rRNA metagenetics. Exposure to environmentally-relevant aqueous concentrations of BaP did not alter expression levels of mRNA for cyp1a1, a “classic” biomarker of exposure to BaP, but resulted in shifts in relative compositions of gut microbiota in females rather than males. Results presented here illustrate that in addition to effects on more well-studied molecular endpoints, relative compositions of the microbiota in guts of fish can also quickly respond to exposure to chemicals, which can provide additional mechanisms for adverse effects on individuals.

Characterizing the gut microbiota in females with infertility and preliminary results of a water-soluble dietary fiber intervention study.

Despite the advances in assisted reproductive technology, approximately 8–12% of the individuals worldwide who are willing to conceive are unable to do so. Fertility depends on a receptive state of the endometrium and hormonal adaptations as well as the immune system. Local and systemic immunities are greatly influenced by the microbiota. The aim of the present study was to compare the gut microbiota in female patients with that in infertility with fertile control subjects and to evaluate the effect of prebiotic partially hydrolyzed guar gum supplementation on gut dysbiosis and the outcome of pregnancy in patients treated with assisted reproductive technology. Dietary fiber can reconstitute the host intestinal microbiota and modify the immune function; however, clinical data regarding the effect of dietary fiber treatment on the success of assisted reproductive technology is lacking. To investigate the gut microbiota in fertile and infertile females, we conducted 16S metagenomic analysis of fecal samples. In total 18 fertile female subjects and 18 patients with infertility matched by age were recruited, and fecal samples were obtained to analyze the gut microbiome using 16S rRNA V3–V4 sequencing. The unweighted and weighted principal coordinate analyses showed a trend indicating microbial structural differences in β-diversity between these two groups. The abundance of the phylum Verrucomicrobia was higher in patients with infertility. At the genus level, a decrease in the abundance of the genera Stenotrophomonas, Streptococcus, and Roseburia and an increase in the abundance of the genera Unclassified [Barnesiellaceae] and Phascolarctobacterium was observed in patients with infertility. Twelve patients agreed to receive the combined therapy comprising embryo transfer by assisted reproductive technology and oral supplementation with partially hydrolyzed guar gum. The success of pregnancy by this combined therapy was 58.3% (7/12), and the failure was 41.7% (5/12). Predictive factors for pregnancy before treatment were characterized by a decrease in the abundance of Paraprevotella and Blautia and an increase in the abundance of Bifidobacterium. Predictive factors for pregnancy before treatment were characterized by a decrease in the abundance of Paraprevotella and Blautia and an increase tendency in the abundance of Bifidobacterium. In conclusion, the present study showed differences in the abundance of gut microbiota between fertile and infertile groups; moreover, partially hydrolyzed guar gum supplementation helped improve gut dysbiosis and the success of pregnancy in females with infertility.

Dietary Polysaccharide from Enteromorpha Clathrata Modulates Gut Microbiota and Promotes the Growth of Akkermansia muciniphila, Bifidobacterium spp. and Lactobacillus spp.

Recently, accumulating evidence has suggested that Enteromorpha clathrata polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has been extensively studied, less consideration has been given to exploring its effect on gut microbiota. In this light, given the critical role of gut microbiota in health and disease, we investigated here the effect of ECP on gut microbiota using 16S rRNA high-throughput sequencing. As revealed by bioinformatic analyses, ECP considerably changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in C57BL/6J mice. However, interestingly, ECP exerted different effects on male and female microbiota. In females, ECP increased the abundances of Bifidobacterium spp. and Akkermansia muciniphila, a next-generation probiotic bacterium, whereas in males, ECP increased the population of Lactobacillus spp. Moreover, by shaping a more balanced structure of the microbiota, ECP remarkably reduced the antigen load from the gut in females. Altogether, our study demonstrates for the first time a prebiotic effect of ECP on gut microbiota and forms the basis for the development of ECP as a novel gut microbiota modulator for health promotion and disease management.

Evidence That the Microbiota Counteracts Male Outbreeding Strategy by Inhibiting Sexual Signaling in Females

The microbiota is increasingly being recognized as having important impacts on many host biological processes. However, evidence of its effects on animal communication and breeding strategy is lacking. In this three-factorial study, we show that females were more willing to mate with related males, with relatedness likely being assessed through the microbiota. By contrast, male mating investment is concurrently determined by both the relatedness and microbiota status of the female. When the microbiota in female Drosophila melanogaster is altered by an antibiotic, male investment in sperm number increased when mating with unrelated females compared to related ones. Contrastingly, the presence of an intact microbiota in females cancelled this male outbreeding strategy. As a consequence, the microbiota, when intact, decreased the fitness of the mating couple. Furthermore, we showed that female sexual signaling (cuticular hydrocarbons), with regards to kin recognition, significantly interacts with microbiota. Interestingly, the interaction is significant for hydrocarbons expressed by both sexes, but not for female-specific compounds. Taken together, our results suggest that microbiota can influence kin recognition by disfavoring male outbreeding strategies, likely by inhibiting key olfactory sexual signaling. This represents the first evidence of a host outbreeding strategy counteracted by their microbiota.

Dietary Keratan Sulfate from Shark Cartilage Modulates Gut Microbiota and Increases the Abundance of Lactobacillus spp.

Keratan sulfate (KS) represents an important family of glycosaminoglycans that are critical in diverse physiological processes. Recently, accumulating evidence has provided a wealth of information on the bioactivity of KS, which established it as an attractive candidate for drug development. However, although KS has been widely explored, less attention has been given to its effect on gut microbiota. Therefore, given that gut microbiota plays a pivotal role in health homeostasis and disease pathogenesis, we investigated here in detail the effect of KS on gut microbiota by high-throughput sequencing. As revealed by heatmap and principal component analysis, the mice gut microbiota was readily altered at different taxonomic levels by intake of low (8 mg/kg) and high dosage (40 mg/kg) of KS. Interestingly, KS exerted a differing effect on male and female microbiota. Specifically, KS induced a much more drastic increase in the abundance of Lactobacillus spp. in female (sixteen-fold) versus male mice (two-fold). In addition, combined with alterations in gut microbiota, KS also significantly reduced body weight while maintaining normal gut homeostasis. Altogether, we first demonstrated a sex-dependent effect of KS on gut microbiota and highlighted that it may be used as a novel prebiotic for disease management.

Structural modulation of gut microbiota by chondroitin sulfate and its oligosaccharide

Chondroitin sulfate (CS) as a dietary supplement and a symptomatic slow acting (SYSA) drug has been used for years. Recently, CS has been demonstrated to be readily degraded and fermented in vitro by specific human gut microbes, hinting that dietary CS may pose a potential effect on gut microbiota composition in vivo. However, until now, little information is available on modulations of gut microbiota by CS. In the present study, modulations of gut microbiota in Kunming mice by CS and its oligosaccharide (CSO) were investigated by high-throughput sequencing. As evidenced by Heatmap and principal component analysis (PCA), the female microbiota were more vulnerable than the male microbiota to CS and CSO treatment. Besides, it is of interest to found that CS and CSO had differing effects on the abundance of Bacteroidales S24-7, Bacteroides, Helicobacter, Odoribacter, Prevotellaceae and Lactobacillus in male mice versus female mice. Collectively, we demonstrated a sex-dependent effect on gut microbiota of CS and CSO. In addition, since gut microbiota exerts a major effect on host physiology, our study highlighted that certain beneficial effects of CS may be associated with modulations of gut microbiota, which merits further investigation.

A role for hormones, gut microbiota and tolerogenic CD103DC in protection of male (NZBxNZW)F1 (BWF1) mice from lupus (MUC8P.805)

Abstract Mechanisms leading to gut homeostasis affect both mucosal and systemic immune function, and involve gut microbiota. Tolerogenic dendritic cells (CD103DC) play a role in gut homeostasis, including generation of induced regulatory T cells (iTregs). Previously, we found that treatment of male BWF1 mice with anti-CD103 antibody significantly increases disease incidence/mortality. Male CD103DC exhibit significantly greater tolerogenic function than either female or castrated male CD103DC in vitro. This study examines the mechanism of sex differences in CD103DC function, and the role of microbiota in lupus. Sex differences in CD103DC function correlated with increased expression of genes associated with tolerogenic/anti-inflammatory function in males, and pro-inflammatory function in females, and changes in iTreg frequency and function in vivo. Male BWF1 CD103DC expressed more Raldh2, an enzyme required for retinoic acid (RA) synthesis and CD103DC function, and supplementation with RA restored tolerogenic function in female CD103DC. Further, we found that male gut microbiota differed significantly from adult, but not immature, female microbiota, suggesting hormones influence the gut microbiota. Importantly, transfer of male gut microbiota to female BWF1 mice significantly reduced anti-dsDNA antibody production. These data suggest that an interplay between hormones, gut microbiota and tolerogenic CD103DC may play a critical role in providing protection to male BWF1 mice.