TO REPLENISH FLORA IN HUMAN COLON AFTER ADMINISTRATION OF ANTIBIOTICS_20241019_001048_0000.pdf

How to replenish flora in human colon by fecal microbiota therapy

1. GUT RENEWAL: UNLOCKING THE POTENTIAL OF FECAL
MICROBIOTA TRANSPLANTATION AND PROBIOTICS
PHARMA XPLORE
INNOVATE.TRANSFORM.THRIVE
EXPLORING THE FUTURE OF PHARMACY INNOVATION

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INTRODUCTION
The gut microbiome refers to the diverse community of microorganisms—bacteria, viruses,
fungi, and other microbes—living in our digestive tract, primarily in the intestines.
This complex ecosystem plays a crucial role in our health by aiding digestion, producing
essential nutrients, regulating the immune system, and protecting against harmful
pathogens.
The balance of these microorganisms can influence various aspects of health, including
metabolism, mental health, and susceptibility to diseases.
Factors such as diet, lifestyle, and antibiotic use can significantly impact the composition of
the gut microbiome.

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Reference: https://www.biocodexmicrobiotainstitute.com/en/gut-microbiota

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FACTORS THAT INFLUENCE GUT MICROBIOTA
Medication use: antibiotics, anti-inflammatories, etc.
Infections (viral gastroenteritis…)
Lifestyle: unbalanced diet (high-fat diet for example), or changes in diet, stress, smoking,
alcoohol excess, etc...
Certain illnesses and injuries
Genetics

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FECAL MICROBIOTA THERAPY (FMT)
Fecal microbiota therapy (FMT) involves transferring fecal matter from a healthy donor to
a recipient to restore gut microbiota balance.
Recently, there have been developments in encapsulating fecal microbiota into tablet form,
making the process more convenient and less invasive compared to traditional enemas or
colonoscopies.
The FDA has approved specific products and protocols for fecal microbiota
transplantation (FMT), Eg: REBYOTA (RBX2660)

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Fecal Microbiota Transplantation (FMT) and probiotics can significantly improve gut
health. The benefits include:
1. Restores gut microbiome balance
2. Reverses dysbiosis (imbalance of gut bacteria)
3. Improves gut barrier function
4. Enhances immune system function
5. Reduces inflammation
6. Treats Clostridioides difficile (C. diff) infections
7. Manages irritable bowel syndrome (IBS) symptoms
8. Supports mental health and cognitive function

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PROBIOTICS
Probiotic Benefits:
1. Maintains gut microbiome balance
2. Enhances gut barrier function
3. Boosts immune system function
4. Reduces inflammation
5. Improves digestion and nutrient absorption
6. Supports mental health and mood
7. May help manage IBS, inflammatory bowel disease (IBD), and allergies
8. Supports healthy weight management

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Combined FMT and Probiotic Benefits:
1. Enhanced gut microbiome diversity and stability
2. Improved gut barrier function and immune response
3. Increased production of beneficial metabolites (e.g., short-chain fatty acids)
4. Reduced symptoms of IBS, IBD, and C. diff infections
5. Improved mental health and cognitive function
6. Enhanced weight management and metabolic health
7. Reduced inflammation and oxidative stress
8. Improved overall gut health and well-being

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The gut microbiota can be replenished by incorporating good microbiomes from
healthy human faeces along with probiotics.
This approach can be personalised according to the gut microbiome of diseased
individuals.
HOW TO REPLENISH THE GUT MICROBIOTA

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STRATEGIES:
"Organ-on-a-chip" technology is a cutting-edge approach that mimics the physiological
functions of human organs, allowing for more accurate studies of drug effects, disease
processes, and interactions with microbiota.
Using gut-on-chip for culturing gut microbiome.
gut-on-chip provide microenvironment for culturing gut microbiome.
pH SENSITIVE ENTERIC COATED PERSONALIZED HARD GEL
CAPSULE CONTAINING STRAINS FROM LYOPHILIZED FAECAL
MICROBIOTA ALONG WITH PROBIOTICS

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Reference:
https://www.mdpi.com/2
313-7673/8/2/226
gut-on-chip

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Endoscopic ultrasound- guided fine needle aspiration (EUS-FNA) can be used for
collecting gut wall epithelium.
After incubation, the cultured microbiome is tested for the presence of all organisms, the
organisms which are in least quantity or are absent are identified.
The fecal microbiota from healthy human volunteers are cultured and the microorganisms
are segregated, cultured individually, collected, lyophilized and pH sensitive enteric coated
to form pellets.
Probiotic bacterium Lactobacillus acidophilus and Bifidobacterium bifidum are cultured,
collected, lyophilized and pH sensitive enteric coated to form pellets.

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After analysing the diseased gut microbiota, the missing microbes are selected from the
pelletized microbiome from healthy individuals, both L.acidophilus and B.bifidum are also
selected.
The above selected gut microbes along with probiotics are packed in eudragit L100 polymer
capsules.
dosage and dosage form
2 billion CFU of required gut microbiome selected
3 billion CFU of each probiotic choosen
oral enteric coated capsules
lyophilized pellets of gut microbiome and probiotics are filled inside the capsules.

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Endoscopic ultrasound- guided fine needle aspiration is used for collecting gut wall
epithelium from diseased individuals
It is placed on gut-on-chip that provide microenvironment for the growth of microbiomes
After incubation,the cultured microbiome is tested for the presence of all organisms, the
organisms which are in least quantity or are absent are identified.
The faecal microbiota from healthy human volunteers are cultered and the microorganisms
are segregated, cultered individually, collected, lyophilized and pH sensitive enteric coated to
form pellets.

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Probiotic bacterium Lactobacillus acidophilus and Bifidobacterium bifidum are cultered,
collected,lyophilized and pH sensitive enteric coated to form pellets.
After analysing the diseased gut microbiota, the missing microbes are selected from the
pelletized microbiome from healthy individuals, both L.acidophilus and B.bifidum are also
selected.
The above selected gut microbes along with probiotics are packed in eudragit L100 polymer
capsules.
The pH sensitive eudraget after oral administration reaches the intestine and releases the
microbiome along with probiotics

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Storage Conditions
1. Temperature: 2-8°C (36-46°F)
2. Humidity: <20% RH (Relative Humidity)
3. Lighting: Protect from direct sunlight
4. Atmosphere: Dry, oxygen-free or nitrogen-filled containers
Containers
Aluminium foils are used for individual packing of capsules and are stored in air tight
containers at conditions mentioned above.

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EVIDENCES
University of California, los Angeles ( UCLA ) have studied on " fecal microbiota
Transplantation for ulcerative colitis " , FMT improved gut health and quality of life.
Stanford University studied on probiotic loaded enteric - coated capsules in gut health ,
have shown that it improved gut barrier function and inflammation problems .
clinical trials : University of Minnesota have sponsored for clinical trials in " Fecal
microbiota Transplantation for clostridoides defficile infection "
Us patent 10, 471 , 111 B2 " Faecal microbiota Transplantation " composition and method
(2019 ) - Assigned to Seres therapeutic.

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There is a growing demand for gut health solutions
There is evidence beyond GI disorders like mental illness , anti - ageing etc
Key focus is on paediatric and geriatric population.
There are already FDA approved formulations available like Rebiotixs RBX 2660,
Probiogens AllFlora probiotic , Openbiomes FMT Capsules etc
Key players already available in the market are Seres therapeutics, OpenBiome , Rebiotix etc
Faecal microbiota Transplantation (FMT) are expected to gain 1.5 billion US Dollars by
2025
25% increase in probiotic sales from , 2019- 2020 .

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FUTURE INNOVATIONS AND CUSTOMIZATION:
Integration with AI and Machine Learning: Combining chip-based microbial growth
platforms with AI and machine learning could enable automated systems that predict
optimal growth conditions, microbial interactions, or drug responses, leading to faster
and more efficient experimentation.
Personalized Lab-on-a-Chip Devices: Customized chips designed for specific microbial
strains or personalized microbiomes could be used in home-based devices, enabling
patients to monitor or manage their own microbiota health in real time.

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In summary, chip-based platforms for microbial colony growth hold significant
promise for advancing research, diagnostics, biomanufacturing, and personalized
medicine. Their ability to precisely control and monitor microbial environments on a
small scale will be essential for future breakthroughs in microbiome science, synthetic
biology, and biotechnology.

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CONCLUSION
pH-sensitive enteric-coated personalized capsules containing lyophilized fecal microbiota and
probiotics represent an exciting frontier in personalized medicine, offering enhanced delivery,
precision-targeted therapy, and the potential for broader applications in both therapeutic and
preventive healthcare. With continued advancements in microbiome science and biotechnology,
these capsules could become a cornerstone in future microbiome-based therapies

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References:
Satya Prakash, Laetitia Rodes, Michael Coussa-Charley & Catherine Tomaro-Duchesneau;
Gut microbiota: next frontier in understanding human health and development of
biotherapeutics . 8 July 2011 , Available from : https://doi.org/10.2147/BTT.S19099
Marla Cunningham et, al ; Shaping the Future of Probiotics and Prebiotics , August 2021 ,
Available from; https://doi.org/10.1016/j.tim.2021.01.003
Matthew Henn, PhD ; Microbiome Live Biotherapeutics as a Novel Approach to Treat
Infectious and Inflammatory Diseases , 27 February 2020 .
The gut microbiota, Biocodex, Microbiota institute. Available from:
https://www.biocodexmicrobiotainstitute.com/en/gut-microbiota

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Rebyota .feacal microbiota . live - jslm , Available from: https://www.rebyota.com/#
VOWST AND THE GUT MICROBIOME VOWST ( faecal microbiota spores, live - brpk)
Available from: https://www.vowst.com/how-vowst-works.
Joanne M. Donkers, Jamie I. van der Vaart and Evita van de Steeg ; Gut-on-a-Chip
Research for Drug Development: Implications of Chip Design on Preclinical Oral
Bioavailability or Intestinal Disease Studies , 28 may 2023 , Available from:
https://www.mdpi.com/2313-7673/8/2/226,