Rumen-mimetic continuous cultivation system

29/07/2026

The following clinical trials involving SCFA supplementation are currently under planning.

1) Effect of Propionic Acid Supplementation on Endothelial Function in Patients with Coronary Artery Disease
ClinicalTrials.gov ID: NCT05135702
Study URL: https://clinicaltrials.gov/study/NCT05135702
Sponsor: Medical College of Wisconsin
Indication: Endothelial function in coronary artery disease
Information provided by Michael E. Widlansky, Medical College of Wisconsin (Responsible Party)
Last Update Posted 2025-09-25 (not yet recruiting at update)

2) Effects of Oral Sodium Butyrate Supplementation on Body Weight Reduction in Overweight/Obese Individuals With and Without Type 2 Diabetes (ButRed)
ClinicalTrials.gov ID NCT07252609
Study URL: https://clinicaltrials.gov/study/NCT07252609
Sponsor Federico II University
Information provided by Giuseppina Costabile, Federico II University (Responsible Party)
Indication: Weight reduction in overweight/obese ± T2D
Last Update Posted 2025-11-26

3) Metabolic Effects of Short-Chain Fatty Acids in Healthy Individuals (SCFA)
ClinicalTrials.gov ID: NCT07183488
Study URL: https://clinicaltrials.gov/study/NCT07183488
Sponsor: University of Copenhagen
Indication: Acute metabolic effects in healthy adults
Information provided by University of Copenhagen (Responsible Party)
Last Update Posted 2026-03-10

4) Evaluating the Effects of Propionate and Butyrate Supplementation on the Intestinal Health of Healthy Volunteers
ClinicalTrials.gov ID: NCT07611370
Study URL: https://clinicaltrials.gov/study/NCT07611370
Sponsor: City of Hope Medical Center
Indication: Intestinal health; feasibility for transplant related GI protection
Information provided by City of Hope Medical Center (Responsible Party)
Last Update Posted 2026-05-28 (not yet recruiting at update)

18/07/2026

Immune protection by SCFAs:
Short chain fatty acids (SCFAs) are immunomodulatory compounds, and have important functions in maintaining the gut barrier, host metabolism, immune tolerance and immunity functions. In autoimmune-associated dysbiosis, the production of SCFAs is frequently altered, which has important ramifications in the immune regulation and pathogenesis of various autoimmune diseases.
SCFAs enhance immune protection by strengthening the epithelial barrier, promoting anti inflammatory signaling, and supporting balanced innate and adaptive immune responses that together maintain mucosal and systemic immune homeostasis. SCFAs strengthen the epithelial barrier by promoting tight junction assembly, boosting mucus production, and reducing inflammation, which together make the gut lining more resistant to physical and microbial disruption.
Pro inflammatory cytokines and SCFAs interact in a regulatory balance where SCFAs suppress cytokine production through anti inflammatory and epigenetic pathways, thereby preventing excessive immune activation and maintaining tissue homeostasis.
NLRP3 inflammasome interacts with SCFAs in a modulatory way, with SCFAs enhancing controlled inflammasome activation while simultaneously limiting excessive inflammation, thereby supporting balanced innate immune responses.
SCFAs promote anti inflammatory macrophage activity by shifting their metabolism toward oxidative pathways and suppressing pro inflammatory cytokine production, thereby reinforcing a tissue protective immune environment.
SCFAs regulate adaptive immunity by enhancing regulatory T cell differentiation, supporting balanced effector T cell function, and shaping antibody responses through metabolic and epigenetic mechanisms that promote controlled, non pathologic immune activation.
Oral administration of propionate and acetate increase Treg frequencies in uterine draining lymph nodes in vivo, providing evidence that specific SCFAs enhance Treg induction in physiological settings such as early pregnancy in pregnant mice.

"Rumen-Mimetic Continuous Cultivation System (RMS)"
- VFA (SCFA) Production from Lignocellulosic Biomass -

04/07/2026

The book "Rumen-Mimetic Continuous Cultivation System (RMS)" describes the production of SCFAs, such as acetate, propionate, and butyrate, from lignocellulosic biomass.

25/06/2026

“This divergence suggests that the ruminal bacterial community underwent a gradual compositional shift that enhanced its ability to digest the mixed substrate of cellulose and starch. Because cellulose is a typical and familiar substrate for ruminal bacteria, the community structure required for its degradation was likely already established, resulting in stable production rates from cellulose alone. Furthermore, the observed increase in VFA production from the mixed substrate may reflect the development of a bacterial community that grows more rapidly through cross feeding interactions. Such a shift would help maintain biomass and prevent washout from the reactor during RMS operation, thereby stabilizing the system over long term cultivation.” (described on p. 66 of this book)

https://amzn.asia/d/0gsqOAlL

07/06/2026

The book “Rumen-Mimetic Continuous Cultivation System: In vitro Rumen Fermentation” is published.

Ruminal bacteria form a diverse community composed of many members that enables efficient and accelerated growth under anaerobic conditions. This community is the result of evolutionary processes that have occurred over billions of years. Their strategy for rapid growth involves cross-feeding and mutualistic interactions without competitive elimination. Consequently, the community can accommodate nutritional disturbances. This ecological adaptability is one of the reasons why we were able to develop the RMS. The remarkable adaptability of ruminal bacteria provides a significant opportunity to engineer or guide microbial communities toward optimized biotechnological production of VFAs from lignocellulosic biomass, as well as toward accurate feed evaluation for raising livestock healthily.

This book introduces a rumen‑mimetic continuous cultivation system (RMS) that enables long‑term, active cultivation of ruminal bacteria and the production of volatile fatty acids (VFAs)—including acetic, propionic, and butyric acids—from lignocellulosic biomass. It also presents a novel proc...

01/06/2026

Rumen-mimetic continuous cultivation system (RMS)

The Kindle e-Book has been published by Amazon.
The paperback will be published soon.

This book describes a rumen mimetic continuous cultivation system (RMS) that enables long term active cultivation of ruminal bacteria and the production of volatile fatty acids (VFAs), such as acetic, propionic, and butyric acids, from lignocellulosic biomass. It also presents a novel in vitro procedure, based on the RMS platform, that allows accurate evaluation of fermentation dynamics and feed quality. Ruminants such as cattle and sheep offer a compelling biological model for these challenges.
We developed an RMS bioreactor specifically designed for the utilization of lignocellulosic biomass to produce VFAs. Human intestinal bacteria influence host physiology and pathophysiology through several pathways, one of which is the microbial production of chemical metabolites, namely VFAs, also known as short chain fatty acids (SCFAs). Ruminal bacteria likewise produce SCFAs in the rumen of cattle. SCFA supplementation has been widely explored as a therapeutic approach, and various health effects of SCFAs have been reported. Therefore, the VFA mixture produced using the RMS bioreactor, with defined purity and impurity profiles, is expected to be suitable for use as food additives and active pharmaceutical ingredients.
We also developed a novel in vitro procedure to elucidate the nutritional value of feedstuffs. This method enables us to measure not only the amount of VFA produced from feed but also the digestion time of the feed. To increase productivity and reduce feed costs per unit of milk or meat in modern cattle production systems, it is important to estimate VFA production rates from feed and to use alternative economical roughage sources. Reliable in vitro evaluation techniques are therefore essential for assessing the fermentation activity of ruminal bacteria and determining the nutritional value of economical feed resources.
Ruminal bacteria form a diverse community composed of many members that enables efficient and accelerated growth under anaerobic conditions. This community is the result of evolutionary processes that have occurred over billions of years. Their strategy for rapid growth involves cross-feeding and mutualistic interactions without competitive elimination. Consequently, the community can accommodate nutritional disturbances. This ecological adaptability is one of the reasons why we were able to develop the RMS. The remarkable adaptability of ruminal bacteria provides a significant opportunity to engineer or guide microbial communities toward optimized biotechnological production of VFAs from lignocellulosic biomass, as well as toward accurate feed evaluation for raising livestock healthily.

21/05/2026

My Kindle e-Book has been published by Amazon.
Its contents are as follows:

INTRODUCTION
Chapter 1: Design of the Rumen-Mimetic Continuous Cultivation System (RMS)
1-1. Collection of rumen fluid from cattle
1-2. Materials and methods used in the RMS
1-3. Operational principles and workflow of the RMS
Chapter 2: Operational Procedures and Functional Behavior of the RMS
2-1. Elimination of ruminal protozoa
2-2. Induction of cellulosomes
2-3. Quantification of volatile fatty acids (VFAs)
2-4. Pulverization of roughage
2-5. Supplementation of alfalfa hay (hay cubes)
2-6. Formation of bacterial flocs and biofilms
2-7. pH dynamics during substrate digestion
2-8. Influence of cultivation pH on bacterial activity
2-9. Nitrogen supply via artificial saliva
2-10. Digestion of cellulose and starch
2-11. Differences in rumen fluid collected from different donor cattle
Chapter 3: Microbial and Physiological Characteristics of the RMS Ecosystem
3-1. PCR-DGGE analysis of microbial community structure
3-2. PCR assays of RMS culture broth
3-3. Digestion of Avicel and feedstuffs within flocs and biofilms
3-4. Carbon-flux estimation during Avicel digestion
3-5. Coupling of catabolism and anabolism and the “catabolic pH shift”
3-6. Catabolic pH shift during carbohydrate digestion
3-7. Kinetic analysis of substrate digestion to measure bacterial activity
3-8. Specific growth rate of ruminal bacteria
Chapter 4: Metabolic Flux Analysis of Substrate Digestion by Ruminal Bacteria
4-1. Stoichiometric metabolic flux analysis of rumen fermentation
4-2. Metabolic flux analysis of alfalfa hay digestion
4-3. Metabolic flux analysis of cellulose and starch digestion
4-4. Effect of rice straw particle size on digestion efficiency
Chapter 5: Application of the RMS for VFA (SCFA) Production from Lignocellulosic Biomass
5-1. Long term cultivation for VFA production
5-2. Effect of pH on metabolic activity
5-3. Fermentation under nitrogen-limited conditions
5-4. VFA (SCFA) production from lignocellulosic biomass using the RMS bioreactor
5-5. Health effects of VFAs (SCFAs): A review
Chapter 6: Application of the RMS in Animal Nutrition and Husbandry
6-1. Monitoring ruminal pH of cattle using a wireless pH electrode
6-2. Nutritional evaluation of feedstuffs based on VFA production
6-3. VFA production from mixed cellulose–starch substrates
6-4. Accessibility of cellulolytic bacteria to roughage cellulose
Acknowledgements
References

This book introduces a rumen‑mimetic continuous cultivation system (RMS) that enables long‑term, active cultivation of ruminal bacteria and the production of volatile fatty acids (VFAs)—including acetic, propionic, and butyric acids—from lignocellulosic biomass. It also presents a novel proc...

10/05/2026

My Kindle e-Book is published by Amazon.

This book introduces a rumen‑mimetic continuous cultivation system (RMS) that enables long‑term, active cultivation of ruminal bacteria and the production of volatile fatty acids (VFAs)—including acetic, propionic, and butyric acids—from lignocellulosic biomass. It also presents a novel proc...

10/05/2026

Our research article published in a scientific journal.

Individual differences in gut microbiota composition highlight the need for methods capable of selectively enriching host-associated bacteria from complex microbial communities. Conventional cultiv...