Researchers from Baylor College of Medicine and Washington University School of Medicine have revealed new findings that could revolutionize the diagnosis and treatment of endometriosis. This gynecological condition, often characterized by ectopic endometrial lesions, pelvic pain, inflammation, and infertility, affects millions of women worldwide. Current diagnosis is invasive, and available treatments offer limited relief, emphasizing the need for novel approaches.

In the study, published in Med (Cell Press), scientists used advanced microbiome-metabolome analyses on stool samples from individuals with and without endometriosis. Through unbiased metabolomics and 16S bacteria sequencing, the researchers identified a distinct bacterial metabolite signature linked to endometriosis. Notably, these findings showed a strong correlation between endometriosis and inflammatory bowel disease (IBD), suggesting common microbial pathways between the two conditions.

One key discovery was the reduced levels of 4-hydroxyindole, a metabolite produced by gut bacteria, in the stool samples of women with endometriosis. Extensive in vivo studies demonstrated that 4-hydroxyindole suppressed the initiation and progression of endometriosis-related inflammation and pain in both murine and human pre-clinical models.

This discovery offers two promising developments: the potential for non-invasive stool-based diagnostic methods and the identification of 4-hydroxyindole as a therapeutic candidate to prevent and treat endometriosis. With this research, scientists hope to offer more effective diagnostic tools and pave the way for microbiota-based therapies for the millions of women affected by this debilitating condition.

Reference:
Talwar et al., Med (2024), https://doi.org/10.1016/j.medj.2024.09.006

A recent study from Stanford University, published in Nature Aging, reveals important insights into the molecular and microbial changes that occur in the human body during aging. The study, led by Dr. Michael P. Snyder and his team, sheds new light on how aging affects the human microbiome, with significant shifts happening around the ages of 44 and 60. These findings have profound implications for human health, especially in relation to cardiovascular health, immune function, and metabolic processes.

Microbiota: A Key Player in Aging

The human microbiota, comprising trillions of microorganisms in the body, plays a pivotal role in maintaining overall health. This study highlights how these microorganisms change in composition and function during the aging process. By tracking more than 135,000 molecules and microbes, the researchers discovered that the microbiome undergoes distinct changes at two key life stages: mid-40s and early 60s.

The study’s findings indicate that these microbial shifts are closely associated with important health concerns, including cardiovascular disease, immune regulation, and metabolism. For example, in participants in their 40s, significant changes were observed in microbes involved in lipid metabolism and alcohol processing, while individuals in their 60s experienced shifts in microbes linked to immune health and kidney function. These discoveries emphasize the importance of microbiota in both the progression of aging and the onset of age-related diseases.

Comprehensive Multi-Omics Profiling

The Stanford team followed 108 participants aged 25 to 75, residing in California, for up to 7 years. The researchers conducted extensive multi-omics profiling, which included the analysis of blood samples and other biological materials every few months. By examining nearly 250 million distinct data points, they were able to track subtle, yet impactful, age-related changes in the participants' molecules and microbiomes.

Dr. Snyder explains that "we are tracking people in incredible detail, measuring as many molecules as possible (tens of thousands) and their microbes to get a detailed picture of their health". This detailed tracking uncovered nonlinear patterns of change, revealing that aging is not a steady process, but instead involves accelerated shifts at specific points in life.

Key Life Stages: Mid-40s and Early 60s

One of the most remarkable findings was the identification of two periods of significant molecular and microbial changes, occurring at approximately 44 and 60 years of age. While age-related decline in the 60s was expected, given the known increase in disease risk and immune system decline, Dr. Snyder and his team were surprised by the marked changes occurring in the mid-40s. This period was associated with shifts in the microbiome and molecules related to cardiovascular disease, lipid and alcohol metabolism, and metabolic processes such as caffeine processing.

The changes in the 60s, on the other hand, included shifts in immune regulation, kidney function, and carbohydrate metabolism, further linking the microbiome to critical age-related health concerns.

Microbiota and Healthspan: Practical Insights

The implications of this study go beyond simply understanding aging - they open the door to practical interventions aimed at improving healthspan. Dr. Snyder emphasizes that by tracking these molecular and microbial changes, individuals can take proactive steps to counter the effects of aging. For instance, individuals in their 40s could focus on managing lipid metabolism and reducing alcohol consumption, while those in their 60s might prioritize immune-boosting strategies and hydration to support kidney health.

The research underscores the crucial role of the microbiome in aging and suggests that monitoring and modulating these microbial communities could offer new pathways for promoting longevity and preventing age-related diseases.

Read the full paper. 

In a study published in Microbiome (BMC by Springer), researchers from the University of Oulu, Finland, have revealed a significant new understanding of the relationship between the maternal microbiota and fetal development. The research highlights the role of extracellular vesicles in the interaction between gut bacteria and the fetus, offering critical insights into prenatal health. Dr. Justus Reunanen, a co-author of the study, will join the Targeting Microbiota 2024 Congress this October in Malta to further elaborate on these findings.

Prior studies on the presence of bacteria in the fetal environment have been limited and contentious. However, this new research reveals extracellular vesicles as a novel mechanism of communication between the maternal microbiota and the fetus, potentially resolving some of the ongoing debates in the field.

The study aimed to investigate whether bacterial extracellular vesicles could be present in the fetal environment during healthy pregnancies and if these vesicles have the ability to cross biological barriers to reach the fetus. The findings were striking: bacterial extracellular vesicles were detectable in the amniotic fluid of healthy pregnant women and closely resembled those originating from the maternal gut microbiota. Additionally, experiments conducted on pregnant mice demonstrated that extracellular vesicles from the maternal gut microbiota could cross biological barriers and reach the intra-amniotic space.

These results suggest a previously unrecognized form of interaction between maternal microbiota and the developing fetus. Extracellular vesicles may play a pivotal role in priming the fetal immune system for gut colonization after birth, potentially influencing early immune system development and prenatal health.

Video Abstract

Join Dr. Justus Reunanen this October in Malta to learn more about microbiota-derived extracellular vesicles for maternal and fetal health.

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Media Credit: Video Abstract, Kaisanlahti, A., Turunen, J., Byts, N. et al. Microbiome 11, 249 (2023).

Researchers from the University of Almeria have published an interesting study highlighting the impact of probiotics on cognitive and emotional functions in healthy older adults. As the global population ages, cognitive decline becomes increasingly prevalent, prompting the need for innovative strategies to address this issue. The study, recently published and registered at ClinicalTrials.gov (NCT04828421), investigates the efficacy of a multi-species probiotic formulation in mitigating age-related cognitive and emotional decline.

The research team conducted a rigorous randomized double-blind placebo-controlled crossover trial involving 33 participants recruited between July 2020 and April 2022. Participants underwent a 10-week intervention where they consumed the assigned probiotic product daily. This was followed by a 4-week washout period before switching to the placebo condition.

The probiotic formulation tested included Lactobacillus rhamnosus and Bifidobacterium lactis. Cognitive function was measured using the Mini-Mental State Examination (MMSE) and the Psychological Experiments Construction Language Test Battery. Emotional health was assessed using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI).

The results of the study were promising, indicating significant improvements in various aspects of cognitive and emotional health:

• Cognitive Function: Participants showed noticeable enhancements in cognitive function, with a mean difference of 1.90 (95% CI 1.09 to 2.70, p < 0.005) as measured by the MMSE.

• Memory: Memory performance also improved significantly, with a mean difference of 4.60 (95% CI 2.91 to 6.29, p < 0.005).

• Depressive Symptoms: There was a marked reduction in depressive symptoms, with a mean difference of 4.09 (95% CI 1.70 to 6.48, p < 0.005).

• Executive Functions: Enhancements were observed in planning and problem-solving skills, selective attention, cognitive flexibility, impulsivity, and inhibitory ability.

This study underscores the potential of probiotics as a therapeutic approach to enhance cognitive and emotional health in older adults. While the findings are encouraging, the researchers emphasize the need for further scientific evidence to substantiate probiotics' role in countering cognitive decline.

Join Targeting Microbiota 2024 this October in Malta to know more about the gut-brain axis.

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Photo credits: kjpargeter - Freepik.

Intermittent fasting combined with protein pacing (IF-P) has emerged as a promising dietary intervention to promote longevity and metabolic health.

A recent study published by researchers from the University of Arizona in Nature Communications explores the effects of IF-P on weight loss, gut microbiome composition, and metabolic pathways. The IF-P regimen involves alternating between days of protein-rich meals and extended fasting periods, significantly impacting longevity-related metabolic processes.

Key findings demonstrate that IF-P enhances gut microbiome diversity, increases beneficial microbial families like Christensenellaceae, and favorably modulates metabolic pathways such as glycine, serine, and threonine metabolism.

Participants adhering to IF-P showed substantial weight loss and improved body composition compared to those on a continuous calorie-restricted diet.

Long-term adherence to IF-P resulted in sustained weight loss and favorable microbiome shifts, suggesting potential long-term benefits for health and longevity.

Intermittent fasting combined with protein pacing (IF-P) offers a promising approach to enhancing longevity and improving overall health. By strategically timing meals and focusing on protein intake, IF-P not only supports weight loss but also positively impacts metabolic pathways and gut microbiome composition. As research continues to uncover the benefits of this dietary regimen, IF-P could become a key strategy in the quest for longer, healthier lives.

Read the full paper.

Photo credits: Image by user14908974 - Freepik.

Bacteriocins, antimicrobial peptides used in food preservation and as alternatives to antibiotics, have garnered interest for their potential as microbiome modulators.

Recently, researchers at the University of Ulm, led by Dr. Christian U. Riedel, established Corynebacterium glutamicum as an effective host for producing various bacteriocins, including garvicin Q (GarQ).

Initially, GarQ production by C. glutamicum reached approximately 7 mg/L in early fermentations, limited by peptide adsorption to the bacterial envelope under neutral pH conditions. To enhance production, the team introduced CaCl2 and Tween 80 supplements, reducing adsorption and boosting GarQ yield to about 15 mg/L. However, Tween 80's use also reduced GarQ activity over time.

Further optimization involved transferring production to a HtrA-deficient C. glutamicum strain, nearly quadrupling GarQ titers to close to 40 mg/L. Low-aeration conditions further improved yields to approximately 100 mg/L, a significant enhancement over previous methods.

Moreover, synthetic variants of GarQ, such as GarQM5F (methionine to phenylalanine substitution at position 5), demonstrated increased efficacy against pathogens like Lactococcus lactis and Listeria monocytogenes.

Article DOI.

Dr. Riedel will present an overview on the identification, production and application of bacteriocins at the Targeting Microbiota 2024 conference. Learn more about Dr. Riedel's talk.

Researchers from the Polytechnic University of Marche in Ancona, Italy, have discovered that the gut bacteria of Antarctic worms act like antifreeze, helping these organisms survive in extreme cold conditions. The study, led by Cinzia Corinaldesi, was published in Science journal.

The research focused on three species of Antarctic polychaetes: Leitoscoloplos geminus, Aphelochaeta palmeri, and Aglaophamus trissophyllus.

These worms have a stable bacterial core dominated by Meiothermus and Anoxybacillus, bacteria which are genetically equipped to produce proteins that function as cryoprotectants. The symbiotic relationship between these bacteria and their worm hosts suggests an evolutionary adaptation that supports the survival of the holobiont in extreme cold.

The discovery of these bacterial cryoprotective proteins holds promise for developing new biotechnological applications based on natural antifreeze mechanisms.

This study underscores the critical role of the microbiome in helping organisms adapt to extreme environments and offers exciting potential for future biotechnological innovations.

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Image Credits.

Researchers from Sorbonne Université and INSEAD shed light on the influence of the gut microbiome on human social decision-making. In a recent study led by Hilke Plassmann, the team conducted a 7-week synbiotic dietary intervention to investigate its effects on altruistic social punishment behavior.

Participants in the study exhibited increased willingness to sacrifice monetary gain when faced with unfair treatment post-intervention,when treated unfairly after the intervention, suggesting a causal link between gut microbiome composition and social decision-making. Changes in fasting-state serum levels of the dopamine-precursor tyrosine were also observed, indicating a potential mechanistic connection along the gut–microbiota–brain-behavior axis.

These findings contribute to our understanding of how body–brain interactions influence social behavior and challenge conventional economic theories. The study underscores the significance of a balanced diet for social decision-making and offers insights with implications for education and policy.

Article DOI.

Targeting Microbiota 2024 will cover the latest research and findings related to microbiota and its modulation. Learn more about the speakers and topics.

Future prospects for leveraging the microbiota as medicine for hypertension (HT)

Recent research, led by Bina Joe from the University of Toledo College of Medicine and Life Sciences, USA, reported a significant link between gut dysbiosis and hypertension, highlighting how alterations in gut microbiota can elevate blood pressure.

• Microbial Metabolites: Short-chain fatty acids (SCFAs), produced by gut bacteria from dietary fibers, play a crucial role in regulating blood pressure by inducing vasodilation.
• Immune System Interaction: Bidirectional communication between the gut microbiota and the immune system influences hypertension, with alterations in gut microbiota composition leading to immune dysregulation.
• Abiotic Factors: Factors like circadian rhythms, age, and diet interact with gut microbiota, impacting blood pressure regulation. Understanding these interactions is vital for personalized treatment approaches. 

Future research will delve into non-bacterial gut microbiota components and develop new personalized treatments for hypertension. Advanced tools like metagenomics, AI, germ-free models, and CRISPR-Cas9 gene editing are driving investigations into the gut microbiota's influence on blood pressure regulation.

Understanding how gut microbiota impacts neural, hormonal, and immune mechanisms informs hypertension and stress response management.

Research aims to personalize hypertension treatments by considering sex-specific gut microbiota differences and medication interactions. Dietary changes, exercise, microbiota bioengineering, and fecal microbiota transplantation offer promising avenues for hypertension management.

Addressing the complexity of study designs and securing funding are essential for moving forward in researching the microbiota's role in hypertension. As scientists uncover more about how the gut microbiota affects blood pressure, we're getting closer to personalized treatments for hypertension.

Article DOI.

Image Credits: Durgan et al. Hypertension. 2024

Recent research published in Trends in Microbiology journal by scientists from the University of Lausanne has clarified new data concerning the small intestinal microbiota (SIM). This study highlights the importance of recent advances in sampling and -omics techniques, which have enabled a more thorough characterization of the SIM.

The small intestinal microbiota (SIM) and the sites of absorption of nutrients. Credits: Yersin, S., & Vonaesch, P. (2024). Trends in Microbiology.

The SIM, a vital component of gastrointestinal health, has long been challenging to study due to sampling limitations and ethical considerations. However, this new research reveals significant findings:

Core Microbiota

The SIM consists of a core microbiota present throughout the small intestinal tract, complemented by segment-specific taxa.

This nuanced understanding provides crucial understanding of the dynamics of the SIM ecosystem.

Functional Roles

The SIM plays key roles in crucial metabolic processes such as carbohydrate degradation, amino acid metabolism, lipid absorption, and micronutrient metabolism.

These functions highlight its importance in overall digestive health and nutrient absorption.

Bacterial Overgrowth

The study identifies two distinct subgroups of small intestinal bacterial overgrowth: small intestinal oral bacterial overgrowth (SIOBO) and coliform small intestinal bacterial overgrowth (SIBO). SIOBO, characterized by an overgrowth of oropharyngeal Gram-positive bacteria, may contribute to conditions such as environmental enteric dysfunction and linear growth delay.

This research increases the understanding of the complexities of the SIM and its implications for human health, allowing new targeted interventions and therapies aimed at optimizing gastrointestinal health.

Dr. Pascale, Vonaesch, lead author of the study, will join Targeting Microbiota 2024 this October to clarify the association of the small intestinal microbiota and disease, and highlight the importance of developing interventions.

Read the full paper.

International Society of Microbiota
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