Can the Microbiome Replace Ozempic? Two Experts Weigh In on This Radical Theory Artwork

Dr. Pepper....Really?

Welcome to "Dr. Pepper...Really," where Dr. Gary Pepper—a board-certified endocrinologist and Associate Professor at a major U.S. medical school—delves into the world of metabolic health. Join him as he interviews individuals sharing their personal journeys with metabolic issues and chats with experts in metabolism, nutrition, thyroid disease, diabetes, hormone imbalances, weight management, and more. The show aims to provide you with valuable insights and perspectives from top professionals on common yet critical issues affecting your health and well-being.

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Dr. Pepper....Really?

Can the Microbiome Replace Ozempic? Two Experts Weigh In on This Radical Theory

May 20, 2025 • Gary Pepper, M.D. • Season 4 • Episode 4

Can the Microbiome Replace Ozempic? Two Experts Weigh In on a Radical Theory
with Dr. Gary Pepper & Mary Gocke, RDN, CDN, CHT

Are we overlooking the natural power of the gut microbiome in managing weight and metabolism?

In this eye-opening conversation, Dr. Gary Pepper — a seasoned endocrinologist — teams up with renowned nutritionist and functional medicine expert Mary Gocke to explore whether the body’s own microbiome might one day rival pharmaceutical GLP-1 drugs like Ozempic and Wegovy. From nutritional strategies to protect muscle and bone during weight loss, to the role of akkermansia and polyphenols in boosting natural GLP-1 production, this discussion offers a radically fresh perspective on sustainable metabolic health.

Topics covered in this episode include:

What GLP-1 medications like Ozempic actually do — and what they don’t

Why weight loss can lead to malnutrition, muscle loss, and even bone density decline

How the gut microbiome — especially Akkermansia muciniphila — may support natural GLP-1 production

The critical importance of dietary fiber, polyphenols, and prebiotics in metabolic health

How protein needs shift during rapid weight loss and how to calculate your target intake

Early evidence for and against the long-term use of GLP-1 drugs

The promising but controversial concept of microdosing and tapering off GLP-1s

Simple strategies to protect your body from the side effects of medical weight loss

Why resistant starches (like cooled potatoes and rice) might actually help your microbiome

The silent risk of osteoporosis from poorly managed weight loss

Whether you're currently on a GLP-1 medication, considering one, or exploring natural alternatives, this candid and science-based conversation will equip you with insights not found in mainstream media.

👉 Visit semagludiet.com to try the free Protein Intake Calculator tailored to your age, weight, activity level, and dietary needs.

📌 This podcast is for educational purposes only. Always consult your healthcare provider before making changes to your medical or nutritional plan.

Gary Pepper, M.D., an associate professor at a prominent medical school and endocrinologist with 40 years of experience, brings clarity to numerous topics within the field of metabolic health. His view points are unhindered by corporate interests, unlike many other current "thought leaders" in medicine. Dr. Pepper, a dedicated educator, established his homebase website www.metabolism.com in 1996 and has blogged on important topics since then. Not one to be left behind by technology he began podcasting in 2020 with the onset of the pandemic and continues publishing vlogs on YouTube at his channel metabolism123. So whatever your choice in media, you will be gaining fresh insights by tuning in to his opinionated shows or reading his blogs on critical health topics.

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When we talk about the microbiome,we're really talking about all thebacteria in the intestine.I think bacteria and yeast, I think thewhole microbiome is--All those little thingsin a living inside of them.That are expressing their DNA.It's amazing thatwe're living in conjunctionwith these living things in our bodies.And for the most part,we're totally unaware of it,except how it might affectexcept how it might affectthings like our appetite,or even our moods, our energy.But it's kind of mysterious.And--[MUSIC PLAYING]Hey, welcome.Welcome back.This is Dr. Gary Pepper.And I'm here today with MaryGocke, a highly accomplishednutritionist.We're going to be doingsomething a little different.We're going to be expanding our horizons.And I think Mary isgoing to be able to bringa whole new dimension toa very important topic.And that is the wholerealm of the GLP1 medications,and weight loss, and howthat can affect your body,as well as just being overweight.So Mary, can you justtell us a little bitabout your background?Sure.I think you referred tome as being accomplished.I don't know how accomplished I am,but I certainly havehad a wonderful career.I'm a registered dietician.And I came into practiceduring the AIDS crisis.And so we were confrontedwith the wasting syndrome.And I actually ended updoing a lot of research.And then around year2000, protease inhibitorscame into play, and peoplestarted to live with AIDS.And around the sametime, there was somethingcalled functionalmedicine coming on the scene.And functional medicine is basicallyan idea of what isgoing wrong with the body.And in that realm,we're looking at nutrition.So it was finally thatnutrition was front and centerin medicine.And so I spent mycareer working with doctorsand providing integrative andfunctional medicine nutrition.And along the way, I'vehad incredible opportunitiesto work with wonderfulclients, wonderful patients.And yeah, I've beenvery blessed and lucky.So what are you doing now?Mostly do a lot of gut work, mostly GI.But again, I'mintrigued by weight loss drugs,like these GLP1 that come on the market.And yeah, and it's fascinating to me.And certainly the nutritional aspect andthe benefits of themis also the downside of them.And what role can I play in that?So it's an interesting class of drugsand certainly has piqued my interest too.You were talking a fewminutes ago about your thoughtsabout obesity in general.And I was wondering if you could justshare a few thoughts abouthow you approach obesity,how you think aboutit, and you could justfill us in a little bit.I think of obesity as sortof a metabolic mess, I'll say.And so when we start to accumulate fatcells or adipocytes,it dysregulates us.Not only does insulinbecome less sensitive,but now we're in an inflammatory statewhere these fat cells haveactually become an organ.And often you can see thatin large bellies on people.And it's become an organ.And it's secreting inflammatory markers.And there's stress on the heart.So we've got all sorts ofblood pressure issues, blood sugarissues.So yes, I look atobesity as a metabolic mess.And how am I going to pull it apart?And how are we going to lose weight?How are you going to approach it?Yes.You had mentioned themicrobiome, the gut.Well, I think that's trueis that obesity certainlydysregulates the microbiome,where now the bacterium arebehaving differently, whether that'sa result of obesity andthe fat cells or the dietor a combination of the two.We now have thismicrobiome that isn't as robustas we'd like to see it in the gut.It's something called akkermansia.And so we'll often see people who areoverweight or carryingmore weight have less akkermansia.And akkermansia isinteresting because it influencesthese L cells in themucosal lining of the GI tract.It influences the production ofglucagon-like peptide,which is GLP1.So we see that this bacterium doesinfluence the production.And now what we're doing is giving GLP1.And GLP1 in the gut isspiked in very brief amount.It sort of rises and falls very quickly.And it's a hormone, soit influences the body.But one of the things that GLP1 doesdecreases appetite.It also makes insulin more sensitive.So if I have somebodywho's carrying excess weight,excess fat cells, I knowinsulin is less sensitive.They're on the road to diabetes.And here we have theseGLP1s that we can giveor that the body will secrete naturally.That makes insulin more sensitive.And yeah, it decreases appetite.It does a couple other things.One of the things I wanted to mention,just for clarification, that whenwe talk about themicrobiome, we're reallytalking about all thebacteria in the intestine.Often bacterium yeast, Ithink the whole microbiome is--All those little things in a living site.That are expressing their DNA.It's amazing thatwe're living in conjunctionwith these living things in our bodies.And for the most part,we're totally unaware of it,except how it mightaffect things like our appetiteor even our moods, our energy.But it's kind of mysterious.And I'd have to say, froma medical point of view,it isn't really very focused upon,certainly in medical school.I never heard a thing about it.And only recently am Iseeing more and more attentionbeing paid to the microbiome.So you mentioned thisacromancia, that it makes GLP1.It's just a mate of a--You want to stimulate the L cells to--So it's not a direct,but it is stimulating--I get it.The L cells to make GLP1 cells.So it's kind of like a homemade ozempic.Exactly.Yeah, we make it.But again, we make itin very brief amount.Maybe it peaks and falls very quickly.And now with these injections, wecan sustain the amount of GLP1 in thesystem systemically.So we're injecting it.Yes.Years ago, when thesedrugs first came to the market,there was something called Bietta.I don't know if youremember that, but Biettawas really the first.It must be at least 10 years ago.And it was given twice a day.Then that changed to something calledVictoza, which was once a day.And then, what do youknow, not too many years go by.And now there's a once a weekversion, which everybody nowis familiar with.I don't think there's many peoplewho are using these othershorter acting medications.Right.That's right.Yeah, it's got a nice history.And wow, here we are today.And it's a very popular drug.And very effective.And effective in lots of ways.But you spoke about the microbiome.And yes, I think as a nutritionist,you start to go like,wow, we can influence it.And we can actuallyinfluence akkermansia by what we eat.And there's a group ofcompounds called polyphenolsthat are in dark chocolate and green teaand most dark colored berries.We can influence theproduction of akkermansiawith thesepolyphenols, with some prebiotics.And so it's of interestto me as a nutritionist.So you can actually talk to theacromancia with nutrients.Dark chocolate polyphenols.Yeah.So a little bit with your green tea.Yeah.So in your experience, how do youapproach that kind of thing?I mean, what do you tell your clients?Now again, this is not medical treatment.This is just educational.Just for the listeners, this is notmeant to replace advice that you get fromyour personal healthcare provider.Well, I'm not opposed to the medications.I certainly am not opposed.I think there's going tobe a place where they'regiven in lower doses fora longer period of time.Because what we don'tknow is long term studies.These drugs have only been around for--I mean, the drugs havebeen around for a long time.But these injectables--ozepic, zepbound, magero, yes.We don't have a lot of longterm studies with these drugs.But I'm not opposed to them.And like I said, maybe thereis a place for microdosing.But I do like to influence people's dietsand suggesting thesepolyphenols and certainlyfibers and prebiotics.So what is a prebiotic anyway?Well, prebiotic is something thatis going to have fiber, right?So we think of notthat anybody eats them,but one of the highest prebioticsis something called Jerusalem artichoke.And so--Jerusalem artichoke.So it's not a very common.But we need fiber.We need to have thesefibers that feed the bacterium.And I'm more interestedin that than certainlygiving a bunch of probiotics.But the prebiotics feed--and the American dietis very low in fiber.We're trying to talkabout 35 grams a day.And so I want to be sure that if I'mworking with somebody who's on a GLP1,that they are increasing their fiberand that they're alsoincreasing their protein.And what kind of things doyou like to give for fiber?Well, I often give a powdered supplement.Because a lot of times,they don't have a big appetite.One of the side effects of GLP1s isthat it decreases emptying time.And so I will do powders.Or just flax seeds.Sometimes I think flax seeds are--Flax seeds is good.Yes.Yeah, absolutely ground up flax seeds.Like freshly ground sothat you can grind them.How about chia seeds?I think they're fine too.I think flax seedsare a little bit better.Because I like the omega-3 fatty acids,which are also beneficialas being anti-inflammatory.But again, I wouldsuggest grinding chia seeds.And people don't recommend that today.People just usually just eat chia seeds.But I like grinding them so that werelease these omega-3 fattyacids and the fiber.So as we're talking aboutthis, one of the concernsthat I have-- and I knowwe've talked about this before--is just the general idea of malnutritionthat's associated with rapid weight loss.And certainly a lot ofpeople on the GLP-1 drugswho are successful atlosing weight will tell me--and I imagine they tellyou too how little they eat.And they're not gettingnearly as many calories,which is really theobjective in the case of weight loss.But they're also not getting theiressential nutrients.And a topic that I like to focus onis muscle lossassociated with the weight loss.And a few studies that I've seen show upto 30% of the weightthat you lose with a GLP-1could be muscle.And we know that weneed muscle for survival,not only to play sports, for example.That's not really what I'm driving at.But in everyday activity, getting around,getting up out of achair, climbing stairs,doing your dailychores, I think losing muscleis a major risk during weight loss.And one of the ideas thatkeeps being thrown aroundis that people whoare on these medicationsor who are losing weight, however,that they need tofocus on not only fiber,but protein, what'syour opinion about that?Yeah, that's a great point.They end up being malnourished.I mean, there's no doubt about itthat you are nottaking in enough caloriesand therefore mobilizing muscle massfor bodily functions just to survive.So yes, an absolutelyprotein, absolutely.Sometimes I'll do a liquid multivitaminand some liquid minerals atdinner, I mean, at bedtime,just so that I can, because again,what people don't realizeis if you take a pill, right,and you're on a GLP1, even aspirin,it's gonna sit in yourstomach for a long time.It's not moving through.So oftentimes, yeah.And I have seenpeople develop ulcerationsfrom taking Advils and so forthbecause the stomach emptying is slowed.So I will use some liquid multivitaminsand minerals at bedtimebecause there's a big risk for fatigueand certainly the loss of muscle mass.But I have had, somebody came to meand they had lost over 100 poundsand I sent them to PTbecause they had lostthe ability of movementand imagine losing100 pounds on your frameand how then do we proceed?How do we move?And you had to reallylearn to build muscle massand of course, he hadn'tchanged his diet at all.So yeah, there's physicians out thereprescribing the medication, great.They see the weight loss.They might see theinsulin become more sensitiveand blood sugars get betterand maybe hypertension comes downand all sorts of benefits,but do we wantsomebody who's malnourishedwho no longer knows how to ambulate?Right, and another thingabout the muscle loss thoughis that not only isnutrition and protein important,but resistancetraining, using the muscles.If you give the muscles enough proteinand then you challenge themwith a little bit of exertionand again, resistancebands I think are very popularand easy and that seems to,that combination really hasa big benefit on muscle mass.But these things are overlookedand they're not as easy as taking thatone injection a weekand we really don'tknow the long-term outcome.As you mentioned, the GLP-1 drugsand we talked about it at the beginningabout how it startedoff with bieta and vitosa.These were for the diabetes treatments.They're not new.So we had a fairlyextensive lead-in period,but as far as treatingobesity with these medications,that's only a few years.I remember when the drugsfirst came out for diabetes,some of the practitionersrecognized the weight loss effectand I'm not going to tell any tales,but I can say that that'swhere people start to go,aha, here's somethingthat causes weight loss.Well, and you can see the public,yeah, the public has jumped on it.We have all these companiesnow providing semi-glutides.So I think the idea ofchanging exercise routine or dietis not in theforefront because they think,oh, I'll just take themeds and lose the weight,but there are downsides.But like I said, I hopeone day there's a placefor like microdosing these because GLP1,it's an incredible hormone.It has a lot of benefits.Well, that brings up thatconcept of what do you dowhen you want to stop taking them?You mentioned microdosingand it's interesting to methat there's so much controversy,at least in the medicalliterature about microdosing.Let's face it, if oneaspirin is a standard doseand you take a half,I mean, what the heck?I mean, I can't seetaking less of a medicationthat has been approved forsomething as being a problem.But yet again, the wheelsof progress turn slowly.I'm a little suspiciousabout in this case why,but I just would mentionthat even though it seemsto make a lot of sense,microdosing is still considereda bit controversial.Or at least a tapering offor weaning off of these drugsbecause I think it'sirresponsible to tell somebodyto stop, you've reachedyour goal and that's it.And if they haven'tmade any changes, then--Well, we know that alarge percentage of peopleregain the weight once they stop.So that is a whole other topic,how to prevent regain ofweight once you decide,well, I'd like to take abreak or for whatever reason,I can't tolerate this.That's why I like this acromancier storybecause this is something that's going oninside our own bodies, but it's not atraditional approach.And I guess a lot moreresearch is necessaryto figure out how toharness things like that.I mean, you can't eatdark chocolate all day longto keep that thing going.The thought has crossed my mind.But it just, inessence, what we're sayingis a colorful diet, right?A varied diet, so I'm noteating the same foods every day,and a diet that's richin fiber and protein.So is there any standard,you can say to the generalpublic about what you wouldconsider a well-rounded dietin terms of how muchfiber, how much protein?Yes, I mean, look, Ithink you can underestimateprotein needs in somebody on a GLP1.And I think it's all, inmy world, individualized.There are some basics that Ithink we should all follow,but when I have somebody on a GLP1,I certainly will go to ahigher level of proteinthan might be calculatedbased on height and weightand activity level.They might, theirneeds might be higher, yes.Right, so we know thatpeople who are losing weightneed a higher amountof protein than somebodywho is sort of on astable weight situation.So the actual losing of weight requiresa higher amount of protein.Yes, and healing and repair of somebodyis certainly in post-op or the proteins.Oh yeah.Yeah, so again,individualized, I have some basic ideasof what I like people tofollow, like I said, variety.Variety is key.We cannot eat thesame foods all the time.The body does not like that.We need a variety ofnutrients that we think about color,and we think aboutgood sources of protein,low toxic burden,pesticides, herbicides, fungicides,keeping those down,keeping plastics out of the body,and then the fiber-rich foods.Yeah.And we can do resistant starches.I like resistant starches.I like rice andpotatoes that are buildingthat resistant starch,meaning they go through digestionwithout beingabsorbed, and so they'll hitthe large bowel wherethe bacteria reside,and they'll feed that bacteria,and we think of it as resistant starch.Oh, that's very interesting.I know so many people areafraid of rice and potatobecause they're carbs, you know,but here there's a highfiber content, I guess,what you're saying.Yeah, resistant.They're not the enemy.No, they're not the enemy, no.(laughs)Yeah, so I would mention one thing.Because of the interestin how much protein peoplemight target in their dietswhile they're losing weightor for whatever reason,there's a website that we havethat's called Semaglue Diet,S-E-M-A-G-L-U-D-I-E-T.com,and we have a free protein calculatorthat takes into accountactivity, age, height, and weight,whether you have aspecial dietary interestlike vegan or low fat,and you can put all that informationand get an estimate, a number,that is in thegeneral recommendation rangefor all those factors.Again, you know, these are just forinformational purposes,but I know a lot ofpeople are sort of in the dark,you know, am I supposed to get 75 grams,am I supposed to get 100 grams?So it's a interesting ballpark kind ofthing that you can do.So I would also want toend here with one commentabout something as well aslosing muscle during weight loss,people could be losing bone mass.And I did a literature searchand I found somecontradictory informationin saying that GLP-1 drugs actually canimprove bone density,but I was skeptical of that.But the one articlethat was what I considermost comprehensiveactually showed bone lossafter one year on medication.So that would be a topic we could,if we can come back to it some point.But osteoporosis is a big problem forpost-metopausal womenbreaking bones is aextremely hazardous outcomeand has very bad prognosis in some cases.And I don't think it's getting nearly theattention that it needs.And the problem being that, you know,good studies will take several years.It's not as easy aswatching the scale go downpound by pound becausebone density changes slowly.But we can talk more about thatand what you might want torecommend or consider doing.So this was very illuminating to meand there are basic thingsthat are not being taught.And this is the kindof information I thinkthat needs to get out there.So do you have any otherquestions or comments before we?I don't think so.It's been a pleasure to be with you.Thank you for having me.Yeah, it's great.I hope we can get youto come back and share.So thanks again forwatching Dr. Pepper, really.And don't forget to comeback here in the near future.We should have moreilluminating topics for you.Stay well.Thank you.(upbeat music)