The Arising · The Microbiome

THE ARISING · LONGEVITY & HEALTHSPAN SUNDAY, OCTOBER 18, 2026 IN THIS EDITION · LONGEVITY & HEALTHSPAN 1 ACOG Now Recommends Hormone Therapy for Many Women With Hot Flashes 2 Cardiologists Urge Doctors to Prescribe Exercise as Routine Heart Care 3 Fasting and Autophagy in Humans: Summary Calls Link Unproven 4 Gut Supplements May Modestly Improve Cognition in Adults Over 60, Review Finds 5 Higher Ultra-Processed Food Intake Linked to Silent Brain Damage on MRI 6 Higher VO2 Max Linked to Lower Depression and Anxiety Risk in UK Biobank 7 Bonn Lab Study Shows Blood Cells From Older Donors Lose Epigenetic Age in a Dish 8 Longer Sleep Linked to Kidney Disease Risk in Type 2 Diabetes LONGEVITY & HEALTHSPAN · WEEKLY READ · 3 MIN AGE AND AGEING · 2 SOURCES Gut Supplements May Modestly Improve Cognition in Adults Over 60, Review Finds Gut supplements are cheap, easy to find and generally low risk. A new review asks whether they might also help older adults think a little more clearly. The answer, so far, is a cautious maybe: the average signal is small, the trials differ widely, and the evidence is limited. he evidence is a systematic review and meta-analysis, published in 2026 in the journal Age and Ageing. It pools earlier trials rather than running a newT one. The team, led by Mary Ni Lochlainn at King's College London, searched four medical databases for studies of adults aged 60 and over. They found 14 that qualified. Thirteen were randomised controlled trials and one was a non- randomised interventional study. Sample sizes in the individual studies ranged from 40 to 120 people. The studies tested three kinds of product. Probiotics are live bacteria. Prebiotics are food ingredients that feed beneficial gut microbes. Synbiotics combine the two. Ten studies tested probiotics, two tested prebiotics and two tested synbiotics. THE ARISING · OCTOBER 18, 2026 PAGE 11 Participants included cognitively healthy older adults (six studies), people with mild cognitive impairment (four) and people with dementia (four). The most common length of treatment was 12 weeks, and the longest was 24 weeks. Nine of the 14 studies reported a statistically significant improvement in at least one area of thinking. The areas named were global cognition (overall mental performance), memory, attention and executive function, which covers planning and mental flexibility. This is not the same as a clean win over placebo: in one dose- comparison trial, the placebo group also improved significantly in memory. Five studies did not report improvement. Two probiotic trials, one prebiotic trial and both synbiotic trials found no significant change in any area. Six of the randomised trials used the same test, the Mini-Mental State Examination, which scores overall cognition. The authors pooled these. Compared with placebo, supplements were linked to a gain of 1.28 points on the test (95% confidence interval 0.15 to 2.40). That is statistically significant, but the range is wide. The lower end is close to no effect. The authors also report substantial heterogeneity, meaning the trials differed a lot from one another in their results. This is a modest average, not a promise for any one person. The result held up in a check that removed trials with moderate or high risk of bias. Four trials remained and the gain was 1.39 points, though the confidence interval again came close to zero (0.03 to 2.75) and the differences between trials were even larger. The authors say the evidence was strongest for global cognition, memory and executive function. They say benefits were seen more consistently in cognitively healthy older adults and those with mild cognitive impairment. What does this mean for someone considering a supplement? The review does not show that any particular product works. The trials used very different bacteria, from single strains to a mix of 18, and doses ranging from 10 million to 50 billion live organisms. The studies were small and short. The review cannot say whether effects last beyond a few months, or whether a few points on a test make a difference in daily life. It also cannot show how the supplements might act on the brain. This is where the argument is weakest: the one pooled result rests on six trials that disagree with each other, and its lower bound is barely above zero. The authors themselves describe the evidence as positive but limited by the small number of high-quality studies. Their conclusion that gut modulation "holds huge promise" is stronger than the data alone firmly support. The TwinsUK press release THE ARISING · OCTOBER 18, 2026 PAGE 12 is more measured. It quotes Ni Lochlainn as saying the findings suggest the approach "could be a promising approach to supporting cognitive health in older adults," while stressing that "more high-quality research is needed." The practical reading is simple. These products are low risk and widely available, according to the authors, and the average signal is small but positive. No one should start or stop any supplement or medication without first talking to their clinician. What to watch next: larger, well-designed trials that test specific products at set doses over longer periods, to show which ones work and for whom. Sources: Age and ageing (2026), TwinsUK / King's College London (Age and Ageing) THE ARISING · OCTOBER 18, 2026 PAGE 13

OCTOBER 15, 2026 | LONGEVITY SPECIAL The bacteria in a baby's gut at 4 months old were linked to how the infant's visual brain was working months later. That is the finding of a study of 194 South African infants, published in mBio in 2025. It is early, observational work, and it makes no claim about lifelong brain health. The bigger idea, that the early gut microbiome shapes brain health across a lifetime, comes from a separate opinion piece in STAT by a program director at a research funder and an advocate. It remains a hypothesis. An infant's development offers a window into relationships that are only beginning to form. This study connects early gut microbes with later visual brain signals over months, a timescale that matters. The study is an observational, longitudinal study in people. It does not test a treatment, and it cannot prove cause and effect. Researchers followed infants from Gugulethu, a community in Cape Town, as part of the Khula Study. Stool samples and brain recordings were collected at up to three visits in the first 18 months of life. The team looked at microbial genes that code for enzymes. These enzymes handle brain-active compounds, according to the paper. The compounds included the neurotransmitters GABA and glutamate, the amino acid tryptophan, and short-chain fatty acids such as acetate and butyrate. The paper says short-chain fatty acids are involved in myelination, the insulation of nerve fibres. Stool samples were sequenced to read the microbes' genes. Brain development was measured with electroencephalography, or EEG. Infants watched a black-and-white checkerboard that flipped every half second. The EEG picked up the brain's response, called the visual-evoked potential. The authors say it reflects how well visual circuits are balanced and how well they are insulated. They pulled six features from it: the timing and size of three signal peaks. The main result concerns timing. According to the authors, microbial gene sets from around 4 months of age were strongly associated with the visual signal at around 9 to 14 months. These forward-looking links were more numerous than links between gut genes and brain signals measured at the same visit. The authors say this suggests early microbial metabolism may affect later neural plasticity and development. That wording is cautious, and it should stay that way. The study shows associations. It does not show that the microbes changed the brain. It measures the gut's genetic potential, not the chemicals actually made. It looks at one brain system, vision, in one community. The abstract does not say whether the findings apply to other groups or whether they relate to health outcomes later in life. The study matters to a longevity audience because of the question behind it. If early gut function does influence brain development, it would add a biological pathway to a story usually told through genes and upbringing. If it does not, the associations may reflect other shared influences, and gut-focused efforts would be off target. Either answer would change where research money and clinical attention go. The STAT opinion piece goes further than the study does. Holly Baines of Wellcome Leap, who directs its $50 million FORM program, and advocate George Vradenburg argue the early gut microbiome may be one way experience and environment shape the brain. They link it to possible effects reaching Alzheimer's disease decades later. They write that cesarean birth, antibiotic use, formula feeding and maternal BMI can contribute to a microbiome that develops off course. The mBio study did not test those exposures or dementia, and the op-ed does not discuss the mBio study. The STAT authors do hedge on their own claims. They write that on autism, causation is not established, and that on dementia the research is only now emerging. They also say they are not arguing against antibiotics, cesarean births or formula. Readers should not start, stop or change any medication, feeding or birth decision without talking to their clinician. The op-ed's central point is about care, not blame. In their words, "the mother's body and the infant's body are one system. We treat them as two." They call for large studies of the gut-brain axis across the life course. They also want biological markers that could flag vulnerability earlier than behavioral screening, which typically starts between 9 and 30 months in the United States, according to the piece. For now, the practical message for adults is modest. The idea that early gut microbes shape lifelong brain health remains a hypothesis. The infant data are suggestive, and the dementia link is more speculative still. What to watch next: larger and longer studies that follow infants beyond 18 months, test whether gut chemistry itself changes, and show whether any of this carries into later cognition. Longer follow-up could show whether the association persists and what it means. For now, the value is in a clearer developmental question, without assigning a child's future. Sources: mBio (2025), STAT (Opinion) ---

OCTOBER 13, 2026 A ketogenic diet sped up tumor growth and shortened survival in mice bred to develop intestinal cancer, according to a new study in Nature, and the cause was not the ketones that the diet is named for. A dietary label can hide substantial biological complexity. Findings in cancer-prone mice show why the tissue, model, and composition of a diet belong beside any claim about its effects. This is animal research. The authors used mouse models of spontaneous intestinal adenoma formation, meaning the animals were genetically prone to developing these growths. The abstract, the only part of the paper available to us, does not give the number of animals. It also does not say how long the mice were fed the diets. No people were studied. The question matters because ketogenic diets are popular for weight loss and are sometimes promoted for longevity. They are very high in fat and very low in carbohydrate. The researchers point out that obesogenic high-fat diets are already known to boost the activity of small-intestinal stem cells and tumor formation. Ketogenic diets contain even more fat, but they also lower circulating insulin and raise ketones. Their effect on intestinal cancer has been poorly understood. According to the study, the ketogenic diet accelerated tumor burden and shortened survival, regardless of ketone metabolites. The team changed the ketone-making pathway in several ways. They blocked or boosted a key ketogenic enzyme, known as HMGCS2, and they disrupted the breakdown of ketones. None of these changes altered tumor development. That points away from ketones as the driver. The evidence points instead to how intestinal cells handle dietary fat. When the researchers removed three related fat-sensing proteins (PPARα, PPARδ and PPARγ) from the intestine, the diet's effects on stem cells weakened. Stem cell expansion, proliferation and the ability to form colonies all dropped. Removing an enzyme called CPT1A, which is needed to burn fatty acids, limited adenoma formation specifically on the ketogenic diet. The authors conclude that tumor initiation is linked to burning dietary fat, not to fat simply building up. The press coverage went further than the abstract in places. According to ScienceDaily, which summarized an MIT release, the small intestine and the colon responded in opposite ways. The ketogenic diet suppressed colon tumors in the mice. The coverage also says the keto-fed mice did not become obese, yet had tumor rates similar to or higher than mice on a high-fat, high-calorie diet. Those details are not in the abstract, so we cannot check them against the study text. "Ketogenic diets have distinct effects on different tissues even within the gastrointestinal tract," senior author Omer Yilmaz of MIT told ScienceDaily. "What might be beneficial for one tissue may be detrimental for another tissue." What does this mean for personal choices? The findings come from genetically engineered mice and may not carry over to people with ordinary cancer risk. The study does not show that keto causes cancer in humans. The authors single out people with familial adenomatous polyposis, an inherited condition with a high risk of small-intestinal tumors. They call for careful thought about diet and cancer prevention in genetically susceptible groups. Nobody should start or stop any diet, treatment or supplement without talking to their clinician, and that applies especially to anyone with an inherited intestinal cancer condition. The study also bears on ketone supplements. According to ScienceDaily, because the effects tracked fat metabolism rather than ketones, ketone drinks would not be expected to reproduce either the harm in the small intestine or the benefit in the colon. That is the coverage's inference, not a test reported in the abstract. The next step is to learn why the same diet pushes neighboring parts of the gut in opposite directions. Researcher Fangtao Chi told ScienceDaily that this is what the team is working on. Human data on ketogenic diets and intestinal tumors, especially in people with inherited risk, will be the key thing to watch. The next experiments can clarify the mechanism. For human nutrition, this remains a reason to ask more precise questions rather than draw a universal conclusion. Sources: Nature (2026), ScienceDaily (MIT; Nature) Nature (2026): https://doi.org/10.1038/s41586-026-10779-y ScienceDaily (MIT; Nature): https://www.sciencedaily.com/releases/2026/10/261002080037.htm ---