Faecal transplants boost immunotherapy

Good news! Fecal transplants keep on giving!

"Three trials provide compelling evidence that faecal microbiota transplantation (FMT) can boost the effectiveness of immunotherapy in advanced solid tumors ... in an analysis of three studies ... But challenges for safety, donor selection and product development remain.

Tumours partially or completely shrunk in 75% of FMT-treated people who underwent immunotherapy with melanoma, 80% of those with non-small cell lung cancer and 50% with metastatic renal cell carcinoma (RCC) across the studies. The only randomized, placebo-controlled trial, which evaluated immunotherapy plus an oral drug with or without FMT in individuals with metastatic RCC, did not find statistically significant 12-month progression-free survival. But it did find that FMT increased the proportion of people whose tumours shrunk (52% versus 32%)."

Nature Briefing: Translational Research

Microbiome modulation in cancer immunotherapy (no public access) "Three landmark trials confirm that fecal microbiota transplantation is a promising approach to enhancing immunotherapy efficacy in advanced solid tumors. The trials also provide insights with major implications for microbiome therapeutic development."

Three studies suggest that FMT improves immunotherapy responsiveness not only by bolstering the growth of good bacteria, which improves the microbiome to help the immune system respond to cancer, but also by killing off bad bacteria.

How donating your poop to a stool bank can save lives

Food for thought and poop! In the past, I have only been a blood donor! 😊 

Where is the next stool bank? 😊 Google says "Yes, there is a stool bank in Arizona, specifically a GoodNature donation center in Tempe." Am I good natured to donate? Tempe here I come! This will be my first poop bank run! 😊

Why does this suggestion come from Down Under? 😊

P.S. Despite all the amusement, this is a serious issue.

"... What’s the take-home message? ..." 

"... As well as blood, plasma and organs, you can now donate fecal samples to stool banks for research and use in transplants. ...

One scientist from the University of New South Wales Sydney (UNSW Sydney) has penned a public service announcement to raise awareness of the emergence and importance of stool banks – and it's something researchers and medical outlets across the world are now also working on. ...

fecal transplantation ... there's growing evidence suggesting it will be a key way to treat a suite of conditions as we learn more about the microbiome and its impact on health. To date, there are studies into how the procedure could benefit treatment of autism spectrum disorder, alcohol use disorder, obesity, melanoma and cancer. Transplants have also been investigated as possible avenues to treat inflammatory bowel and liver diseases, long-term urinary tract infections and much more. ..."

How donating your poop to a stool bank can save lives

How to donate your poo to science or medicine "The microbes in your poo could be a gift to others. Here’s what to think about if you’re interested in donating your poo."

How to donate your poo to science or medicine (the article as it appeared originally in The Conversation)

Microbiome may determine the temperament of babies

Amazing stuff! I am not sure this study resolved the chicken and egg issue or what came first. Did the microbiome influence the temperament or vice versa.

"... a new preprint, may be differences in their microbiomes.

Previous studies have drawn connections between microbiome composition and certain temperament traits. 

But it’s hard to tell the chicken from the egg: Do kids who behave certain ways end up with a specific mix of microbes, or do some microbes influence the way kids behave? ...

They gathered four exuberant 2.5-year-old toddlers and four more inhibited ones. ... The team obtained fecal samples from all the toddlers, then prepared a bunch of rats for a poo transfusion by essentially rinsing the microbes from their bowels before giving them a filtered stool sample or a sham control, followed by booster inoculations 2 and 3 days later.

Rats that received exuberant toddler poo were more exploratory in standard lab tests than both the rats that received samples from the inhibited kids and the control rats. 

Intriguingly, although the rats that received the inhibited kids’ stools didn’t show significant behavioral differences from the controls, a part of their brains showed reduced dopamine signaling, which could indicate that they felt less “reward” from joyful activities. ..."

From the abstract:

"Background

Behavioural phenotypes have previously been transferred via faecal microbiota transplantation (FMT) from patients with psychiatric disorders to rodents. Studies indicate that the gut microbiota composition may be linked to certain temperament traits, defined as biologically-based differences in emotional reactivity and self-regulation. Here, we aimed to determine if the gut microbiota plays a role in temperament using an FMT approach. We focused on the temperament traits of exuberance, defined as positive reactivity, decreased behavioural inhibition, and high behavioural approach tendencies.

Methods

Faeces from 2.5-year-old toddlers from FinnBrain Birth Cohort Study with high exuberance/approach or high behavioural inhibition in the LabTAB bubbles-episode was transferred to juvenile male Sprague Dawley rats (age 22/23 days). Behaviour of the rat recipients (n=53) was assessed using the novel non-social arena, novel social arena, hole board test for exploratory behaviour, social approach-avoidance test, and forced swim test. The faecal pellets collected from the rodents were analyzed with 16s rRNA sequencing and faecal samples from the sample of toddlers (which included the donors, n=176) were analysed using short-read metagenomic sequencing. The striatum and prefrontal cortex from the rodents’ brains were analysed post-mortem using RNAseq.

Results

Microbiome from toddlers with high exuberance traits induced increased exploratory behaviour compared to vehicle-controls and rats receiving faeces from inhibited toddlers.

Locomotor activity, social, and depressive-like behaviour remained unaffected. We noted a downregulation of the dopamine synapse pathway within the striatum of the rats that received faeces from the inhibited trait donors compared with vehicle-controls. Faecal microbiota of rats receiving faeces from the same donor resembled more each other than rats from a different cage. Clostridium species AM29 11AC in toddler microbiome was positively related to exuberance, but there were no cross-sectional associations between faecal metabolites in the human sample.

Conclusions

FMT from exuberant toddlers lead to altered exploratory-related behaviour in rats."

ScienceAdviser

Faecal transplantation from exuberant toddlers increases exploratory behaviour in rats (preprint, open access)

Figure 1. Schematic of the animal experiment timeline. 

Figure 3. Pathway analysis of differentially expressed genes in striatum in recipients of inhibited toddler’s faeces vs controls were not statistically significant.

More than 70 babies have been born from uterus transplants: ‘It’s a complete new world’

When will we be able to perform pregnancy and birth in vitro? I bet in the next 10-25 years.

Imagine a time e.g. when all the past hyperpartisan fights over abortion will be history and forgotten.

But this research is also a cautionary tale, because of the reported common adverse events. Furthermore, the data underlying this study is very old dating back to 2019.

From the key points and abstract:

"Key Points

Question

Is uterus transplant safe and feasible, resulting in subsequent live births?

Findings

In this series of 20 participants, uterus allograft was successful in 70% of recipients and was associated with at least 1 live birth for all recipients with a successful allograft. Adverse events were common, with medical and surgical risks affecting recipients as well as donors.

Meaning

Uterus transplant was feasible and was associated with at least 1 subsequent live birth following a successful allograft.

Abstract

Importance

Uterus transplant in women with absolute uterine-factor infertility offers the possibility of carrying their own pregnancy.

Objective

To determine whether uterus transplant is feasible and safe and results in births of healthy infants.

Design, Setting, and Participants

A case series including 20 participants with uterine-factor infertility and at least 1 functioning ovary who underwent uterus transplant in a large US tertiary care center between September 14, 2016, and August 23, 2019.

Intervention

The uterus transplant (from 18 living donors and 2 deceased donors) was surgically placed in an orthotopic position with vascular anastomoses to the external iliac vessels. Participants received immunosuppression until the transplanted uterus was removed following 1 or 2 live births or after graft failure.

Main Outcomes and Measures

Uterus graft survival and subsequent live births.

Results

Of 20 participants (median age, 30 years [range, 20-36]; 2 Asian, 1 Black, and 16 White), 14 (70%) had a successful uterus allograft; all 14 recipients gave birth to at least 1 live-born infant. Eleven of 20 recipients had at least 1 complication. Maternal and/or obstetrical complications occurred in 50% of the successful pregnancies, with the most common being gestational hypertension (2 [14%]), cervical insufficiency (2 [14%]), and preterm labor (2 [14%]). Among the 16 live-born infants, there were no congenital malformations. Four of 18 living donors had grade 3 complications.

Conclusions and Relevance

Uterus transplant was technically feasible and was associated with a high live birth rate following successful graft survival. Adverse events were common, with medical and surgical risks affecting recipients as well as donors. Congenital abnormalities and developmental delays have not occurred to date in the live-born children."

Uterus transplant science has entered 'a complete new world' "In a study of 20 women who had uterus transplants, 14 went on to deliver a baby."

Uterus Transplant in Women With Absolute Uterine-Factor Infertility (no public access)

Fecal transplants reverse signs of brain aging in mice

Feeling old, tried this one before? How dependent are humans on their microbiota?

"... Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. ..."

New poo, new you? Fecal transplants reverse signs of brain aging in mice | Science | AAAS

Microbiota from young mice counteracts selective age-associated behavioral deficits